| Subject | Object |
|---|---|
| dailymed-drugs:746 |
None
|
| dailymed-drugs:1775 |
None
|
| dailymed-drugs:2689 |
None
|
| dailymed-drugs:2750 |
None
|
| dailymed-drugs:625 |
None
|
| dailymed-drugs:65 |
None.
|
| dailymed-drugs:294 |
None.
|
| dailymed-drugs:502 |
None.
|
| dailymed-drugs:578 |
None.
|
| dailymed-drugs:592 |
None.
|
| dailymed-drugs:640 |
None.
|
| dailymed-drugs:1492 |
None.
|
| dailymed-drugs:1683 |
None.
|
| dailymed-drugs:1765 |
None.
|
| dailymed-drugs:2957 |
None.
|
| dailymed-drugs:3140 |
None.
|
| dailymed-drugs:3436 |
None.
|
| dailymed-drugs:3491 |
None.
|
| dailymed-drugs:3989 |
None.
|
| dailymed-drugs:4065 |
None.
|
| dailymed-drugs:321 |
None known.
|
| dailymed-drugs:653 |
None known.
|
| dailymed-drugs:1620 |
None known.
|
| dailymed-drugs:4200 |
None known.
|
| dailymed-drugs:100 |
Lactic Acidosis:: Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with RIOMET; when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis may also occur in association with a number of pathophysiologic conditions, including diabetes mellitus, and whenever there is significant tissue hypoperfusion and hypoxemia. Lactic acidosis is characterized by elevated blood lactate levels (>5 mmol/L), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. When metformin is implicated as the cause of lactic acidosis, metformin plasma levels>5��g/mL are generally found. The reported incidence of lactic acidosis in patients receiving metformin hydrochloride is very low (approximately 0.03 cases/1000 patient-years, with approximately 0.015 fatal cases/1000 patient-years). In more than 20,000 patient-years exposure to metformin in clinical trials, there were no reports of lactic acidosis. Reported cases have occurred primarily in diabetic patients with significant renal insufficiency, including both intrinsic renal disease and renal hypoperfusion, often in the setting of multiple concomitant medical/surgical problems and multiple concomitant medications. Patients with congestive heart failure requiring pharmacologic management, in particular those with unstable oracute congestive heart failure who are at risk of hypoperfusion and hypoxemia, are at increased risk of lactic acidosis. The risk of lactic acidosis increases with the degree of renal dysfunction and the patient's age. The risk of lactic acidosis may, therefore, be significantly decreased by regular monitoring of renal function in patients taking RIOMET and by use of the minimum effective dose of RIOMET. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. RIOMET treatment should not be initiated in patients���80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced, as these patients are more susceptible to developing lactic acidosis. In addition, RIOMET should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration, or sepsis. Because impaired hepatic function may significantly limit the ability to clear lactate, RIOMET should generally be avoided in patients with clinical or laboratory evidence of hepatic disease. Patients should be cautioned against excessive alcohol intake, either acute or chronic, when taking RIOMET, since alcohol potentiates the effects of metformin hydrochloride on lactate metabolism. In addition, RIOMET should be temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure (see also PRECAUTIONS). The onset of lactic acidosis often is subtle, and accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. There may be associated hypothermia, hypotension, and resistant bradyarrhythmias with more marked acidosis. The patient and the patient's physician must be aware of the possible importance of such symptoms and the patient should be instructed to notify the physician immediately if they occur (see also PRECAUTIONS). RIOMET should be withdrawn until the situation is clarified. Serum electrolytes, ketones, blood glucose and, if indicated, blood pH, lactate levels, and even blood metformin levels may be useful. Once a patient is stabilized on any dose level of RIOMET, gastrointestinal symptoms, which are common during initiation of therapy, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease. Levels of fasting venous plasma lactate above the upper limit of normal but less than 5 mmol/L in patients taking RIOMET do not necessarily indicate impending lactic acidosis and may be explainable by other mechanisms, such as poorly controlled diabetes or obesity, vigorous physical activity, or technical problems in sample handling. (See also PRECAUTIONS.) Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia). Lactic acidosis is a medical emergency that must be treated in a hospital setting. In a patient with lactic acidosis who is taking RIOMET, the drug should be discontinued immediately and general supportive measures promptly instituted. Because metformin hydrochloride is dialyzable (with a clearance of up to 170 mL/min under good hemodynamic conditions), prompt hemodialysis is recommended to correctthe acidosis and remove the accumulated metformin. Such management often results in prompt reversal of symptoms and recovery. (See also CONTRAINDICATIONS and PRECAUTIONS.)
|
| dailymed-drugs:757 |
Lactic Acidosis: Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with metformin hydrochloride tablets or metformin hydrochloride extended-release tablets; when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis may also occur in association with a number of pathophysiologic conditions, including diabetes mellitus, and whenever there is significant tissue hypoperfusion and hypoxemia. Lactic acidosis is characterized by elevated blood lactate levels (>5 mmol/L), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. When metformin is implicated as the cause of lactic acidosis, metformin plasma levels>5 mcg/mL are generally found. The reported incidence of lactic acidosis in patients receiving metformin hydrochloride is very low (approximately 0.03 cases/1000 patient-years, with approximately 0.015 fatal cases/1000 patient-years). In more than 20,000 patients-years exposure to metformin in clinical trials, there were no reports of lactic acidosis. Reported cases have occurred primarily in diabetic patients with significant renal insufficiency, including both intrinsic renal disease and renal hypoperfusion, often in the setting of multiple concomitant medical/surgical problems and multiple concomitant medications. Patients with congestive heart failure requiring pharmacologic management, in particular those with unstable or acute congestive heart failure who are at risk of hypoperfusion and hypoxemia, are at increased risk of lactic acidosis. The risk of lactic acidosis increases with the degree of renal dysfunction and the patient's age. The risk of lactic acidosis may, therefore, be significantly decreased by regular monitoring of renal function in patients taking metformin hydrochloride tablets or metformin hydrochloride extended-release tablets and by use of the minimum effective dose of metformin hydrochloride tablets or metformin hydrochloride extended-release tablets. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. Metformin hydrochloride tablets or metformin hydrochloride extended-release tablets treatment should not be initiated in patients���80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced, as these patients are more susceptible to developing lactic acidosis. In addition, metformin hydrochloride tablets and metformin hydrochloride extended-release tablets should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration, or sepsis. Because impaired hepatic function may significantly limit the ability to clear lactate, metformin hydrochloride tablets and metformin hydrochloride extended-release tablets should generally be avoided in patients with clinical or laboratory evidence of hepatic disease. Patients should be cautioned against excessive alcohol intake, either acute or chronic, when taking metformin hydrochloride tablets or metformin hydrochloride extended-release tablets, since alcohol potentiates the effects of metformin hydrochloride on lactate metabolism. In addition, metformin hydrochloride tablets and metformin hydrochloride extended-release tablets should be temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure (see also PRECAUTIONS). The onset of lactic acidosis often is subtle, and accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. There may be associated hypothermia, hypotension, and resistant bradyarrhythmias with more marked acidosis. The patient and the patient's physician must be aware of the possible importance of such symptoms and the patient should be instructed to notify the physician immediately if they occur (see also PRECAUTIONS). Metformin hydrochloride tablets and metformin hydrochloride extended-release tablets should be withdrawn until the situation is clarified. Serum electrolytes, ketones, blood glucose and if indicated, blood pH, lactate levels, and even blood metformin levels may be useful. Once a patient is stabilized on any dose level of metformin hydrochloride tablets or metformin hydrochloride extended-release tablets, gastrointestinal symptoms, which are common during initiation of therapy, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease. Levels of fasting venous plasma lactate above the upper limit of normal but less than 5 mmol/L in patients taking metformin hydrochloride tablets or metformin hydrochloride extended-release tablets do not necessarily indicate impending lactic acidosis and may be explainable by other mechanisms, such as poorly controlled diabetes or obesity, vigorous physical activity, or technical problems in sample handling. (See also PRECAUTIONS.) Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia). Lactic acidosis is a medical emergency that must be treated in a hospital setting. In a patient with lactic acidosis who is taking metformin hydrochloride tablets or metformin hydrochloride extended-release tablets, the drug should be discontinued immediately and general supportive measures promptly instituted. Because metformin hydrochloride is dialyzable (with a clearance of up to 170 mL/min under good hemodynamic conditions), prompt hemodialysis is recommended to correct the acidosis and remove the accumulated metformin. Such management often results in prompt reversal of symptoms and recovery. (See also CONTRAINDICATIONS and PRECAUTIONS).
|
| dailymed-drugs:1121 |
Lactic Acidosis: Lactic acidosis is a rare, but serious, metabolic complication
that can occur due to metformin accumulation during treatment with GLUCOPHAGE
or GLUCOPHAGE XR; when it occurs, it is fatal in approximately 50% of cases.
Lactic acidosis may also occur in association with a number of pathophysiologic
conditions, including diabetes mellitus, and whenever there is significant
tissue hypoperfusion and hypoxemia. Lactic acidosis is characterized by elevated
blood lactate levels (>5 mmol/L), decreased blood pH, electrolyte disturbances
with an increased anion gap, and an increased lactate/pyruvate ratio. When
metformin is implicated as the cause of lactic acidosis, metformin plasma
levels>5��g/mL are generally found. The reported incidence of lactic acidosis in patients receiving
metformin hydrochloride is very low (approximately 0.03 cases/1000 patient-years,
with approximately 0.015 fatal cases/1000 patient-years). In more than 20,000
patient-years exposure to metformin in clinical trials, there were no reports
of lactic acidosis. Reported cases have occurred primarily in diabetic patients
with significant renal insufficiency, including both intrinsic renal disease
and renal hypoperfusion, often in the setting of multiple concomitant medical/surgical
problems and multiple concomitant medications. Patients with congestive heart
failure requiring pharmacologic management, in particular those with unstable
or acute congestive heart failure who are at risk of hypoperfusion and hypoxemia,
are at increased risk of lactic acidosis. The risk of lactic acidosis increases
with the degree of renal dysfunction and the patient's age. The risk of lactic
acidosis may, therefore, be significantly decreased by regular monitoring
of renal function in patients taking GLUCOPHAGE or GLUCOPHAGE XR and by use
of the minimum effective dose of GLUCOPHAGE or GLUCOPHAGE XR. In particular,
treatment of the elderly should be accompanied by careful monitoring of renal
function. GLUCOPHAGE or GLUCOPHAGE XR treatment should not be initiated in
patients���80 years of age unless measurement of creatinine clearance demonstrates
that renal function is not reduced, as these patients are more susceptible
to developing lactic acidosis. In addition, GLUCOPHAGE and GLUCOPHAGE XR should
be promptly withheld in the presence of any condition associated with hypoxemia,
dehydration, or sepsis. Because impaired hepatic function may significantly
limit the ability to clear lactate, GLUCOPHAGE and GLUCOPHAGE XR should generally
be avoided in patients with clinical or laboratory evidence of hepatic disease.
Patients should be cautioned against excessive alcohol intake, either acute
or chronic, when taking GLUCOPHAGE or GLUCOPHAGE XR, since alcohol potentiates
the effects of metformin hydrochloride on lactate metabolism. In addition,
GLUCOPHAGE and GLUCOPHAGE XR should be temporarily discontinued prior to any
intravascular radiocontrast study and for any surgical procedure . The onset of lactic acidosis often is subtle, and accompanied
only by nonspecific symptoms such as malaise, myalgias, respiratory distress,
increasing somnolence, and nonspecific abdominal distress. There may be associated
hypothermia, hypotension, and resistant bradyarrhythmias with more marked
acidosis. The patient and the patient's physician must be aware of the possible
importance of such symptoms and the patient should be instructed to notify
the physician immediately if they occur .
GLUCOPHAGE and GLUCOPHAGE XR should be withdrawnuntil the situation is clarified.
Serum electrolytes, ketones, blood glucose, and if indicated, blood pH, lactate
levels, and even blood metformin levels may be useful. Once a patient is stabilized
on any dose level of GLUCOPHAGE or GLUCOPHAGE XR, gastrointestinal symptoms,
which are common during initiation of therapy, are unlikely to be drug related.
Later occurrence of gastrointestinal symptoms could be due to lactic acidosis
or other serious disease. Levels of fasting venous plasma lactate above the upper
limit of normal but less than 5 mmol/L in patients
taking GLUCOPHAGE or GLUCOPHAGE XR do not necessarily indicate impending lactic
acidosis and may be explainable by other mechanisms, such as poorly controlled
diabetes or obesity, vigorous physical activity, or technical problems in
sample handling. Lactic acidosis should be suspected in any diabetic patient
with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia). Lactic acidosis is a medical emergency that must be treated
in a hospital setting. In a patient with lactic acidosis who is taking GLUCOPHAGE
or GLUCOPHAGE XR, the drug should be discontinued immediately and general
supportive measures promptly instituted. Because metformin hydrochloride is
dialyzable (with a clearance of up to 170 mL/min under good
hemodynamic conditions), prompt hemodialysis is recommended to correct the
acidosis and remove the accumulated metformin. Such management often results
in prompt reversal of symptoms and recovery.
|
| dailymed-drugs:1314 |
Lactic Acidosis: Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with metformin; when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis may also occur in association with a number of pathophysiologic conditions, including diabetes mellitus, and whenever there is significant tissue hypoperfusion andhypoxemia. Lactic acidosis is characterized by elevated blood lactate levels (>5 mmol/L), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. When metformin is implicated as the cause of lactic acidosis, metformin plasma levels>5��g/mL are generally found. The reported incidence of lactic acidosis in patients receiving metformin hydrochloride is very low (approximately 0.03 cases/1000 patient-years, with approximately 0.015 fatal cases/1000 patient-years). In more than 20,000 patient-years exposure to metformin in clinical trials, there were no reports of lactic acidosis. Reported cases have occurred primarily in diabetic patients with significant renal insufficiency, including both intrinsic renal disease and renal hypoperfusion, often in the setting of multiple concomitant medical/surgical problems and multiple concomitant medications. Patients with congestive heart failure requiring pharmacologic management, in particular those with unstable or acute congestive heart failure who are at risk of hypoperfusion and hypoxemia, are at increased risk of lactic acidosis. The risk of lactic acidosis increases with the degree of renal dysfunction and the patient's age. The risk of lactic acidosis may, therefore, be significantly decreased by regular monitoring of renal function in patients taking metformin and by use of the minimum effective dose of metformin. In particular, treatment of the elderly should be accompaniedby careful monitoring of renal function. Metformin treatment should not be initiated in patients���80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced, as these patients are more susceptible to developing lactic acidosis. In addition, metformin should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration, or sepsis. Because impaired hepatic function may significantly limit the ability to clear lactate, metformin should generally be avoided in patients with clinical or laboratory evidence of hepatic disease. Patients should be cautioned against excessive alcohol intake, either acute or chronic, when taking metformin, since alcohol potentiates the effects of metformin hydrochloride on lactate metabolism. In addition, metformin should be temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure (see also PRECAUTIONS). The onset of lactic acidosis often is subtle, and accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. There may be associated hypothermia, hypotension, and resistant bradyarrhythmias with more marked acidosis. The patient and the patient's physician must be aware of the possible importance of such symptoms and the patient should be instructed to notify the physician immediately if they occur (see also PRECAUTIONS). Metformin should be withdrawn until the situation is clarified. Serum electrolytes, ketones, blood glucose and, if indicated, blood pH, lactate levels, and even blood metformin levels may be useful. Once a patient is stabilized on any dose level of metformin, gastrointestinal symptoms, which are common during initiation of therapy, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease. Levels of fasting venous plasma lactate above the upper limit of normal but less than 5 mmol/L in patients taking metformin do not necessarily indicate impending lactic acidosis and may be explainable by other mechanisms, such as poorly controlled diabetes or obesity, vigorous physical activity, or technical problems in sample handling. (See also PRECAUTIONS.) Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia). Lactic acidosis is a medical emergency that must be treated in a hospital setting. In a patient with lactic acidosis who is taking metformin, the drug should be discontinued immediately and general supportive measures promptly instituted. Because metformin hydrochloride is dialyzable (with a clearance of up to 170 mL/min under good hemodynamic conditions), prompt hemodialysis is recommended to correct the acidosis and remove the accumulated metformin. Such management often results in prompt reversal of symptomsand recovery. (See also CONTRAINDICATIONS and PRECAUTIONS.)
|
| dailymed-drugs:1822 |
WARNING: Thyroid hormones, including LEVOXYL, either alone or with other therapeutic agents, should not be used for the treatment of obesity or for weight loss. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or even life threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects.
|
| dailymed-drugs:2633 |
BOXED WARNING: Lactic Acidosis: Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with metformin; when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis may also occur in association with a number of pathophysiologic conditions, including diabetes mellitus, and whenever there is significant tissue hypoperfusion and hypoxemia. Lactic acidosis is characterized by elevated blood lactate levels (>5 mmol/L), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. When metformin is implicated as the cause of lactic acidosis, metformin plasma levels>5��g/mL are generally found. The reported incidence of lactic acidosis in patients receiving metformin hydrochloride is very low (approximately 0.03 cases/1000 patient-years, with approximately 0.015 fatal cases/1000 patient years). In more than 20,000 patient-years exposure to metformin in clinical trials, there were no reports of lactic acidosis. Reported cases have occurred primarily in diabetic patients with significant renal insufficiency, including both intrinsic renal disease and renal hypoperfusion, often in the setting of multiple concomitant medical/surgical problems and multiple concomitant medications. Patients with congestive heart failure requiring pharmacologic management, in particular those with unstable or acute congestive heart failure who are at risk of hypoperfusion and hypoxemia, are at increased risk of lactic acidosis. The risk of lactic acidosis increases with the degree of renal dysfunction and the patient's age. The risk of lactic acidosis may, therefore, be significantly decreased by regular monitoring of renal function in patients taking metformin and by use of the minimum effective dose of metformin. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. Metformin treatment should not be initiated in patients���80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced, as these patients are more susceptible to developing lactic acidosis. In addition, metformin should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration, or sepsis. Because impaired hepatic function may significantly limit the ability to clear lactate, metformin should generally be avoided in patients with clinical or laboratory evidence of hepatic disease.Patients should be cautioned against excessive alcohol intake, either acute or chronic, when taking metformin, since alcohol potentiates the effects of metformin hydrochloride on lactate metabolism. In addition, metformin should be temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure . The onset of lactic acidosis often is subtle, and accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. There may be associated hypothermia, hypotension, and resistant bradyarrhythmias with more marked acidosis. The patient and the patient's physician must be aware of the possible importance of such symptoms and the patient should be instructed to notify the physician immediately if they occur . Metformin should be withdrawn until the situation is clarified. Serum electrolytes, ketones, blood glucose, and if indicated, blood pH, lactate levels, and even blood metformin levels may be useful. Once a patient is stabilized on any dose level of metformin, gastrointestinal symptoms, which are common during initiation of therapy, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease. Levels of fasting venous plasma lactate above the upper limit of normal but less than 5 mmol/L in patients taking metformin do not necessarily indicate impending lactic acidosis and may be explainable by other mechanisms, such as poorly controlled diabetes or obesity, vigorous physical activity, or technical problems in sample handling. Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia). Lactic acidosis is a medical emergency that must be treated in a hospital setting. In a patient with lactic acidosis who is taking metformin, the drug should be discontinued immediately and general supportive measures promptly instituted. Because metformin hydrochloride is dialyzable (with a clearance of up to 170 mL/min under good hemodynamic conditions), prompt hemodialysis is recommended to correct the acidosis and remove the accumulated metformin. Such management often results in prompt reversal of symptoms and recovery.
|
| dailymed-drugs:2713 |
Lactic Acidosis:: Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with metformin; when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis may also occur in association with a number of pathophysiologic conditions, including diabetes mellitus, and whenever there is significant tissue hypoperfusion and hypoxemia. Lactic acidosis is characterized by elevated blood lactate levels (>5 mmol/L), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. When metformin is implicated as the cause of lactic acidosis, metformin plasma levels>5 mcg/mL are generally found. The reported incidence of lactic acidosis in patients receiving metformin hydrochloride is very low (approximately 0.03 cases/1000 patient-years, with approximately 0.015 fatal cases/1000 patient-years). In more than 20,000 patient-years exposure to metformin in clinical trials, there were no reports of lactic acidosis. Reported cases have occurred primarily in diabetic patients with significant renal insufficiency, including both intrinsic renal disease and renal hypoperfusion, often in the setting of multiple concomitant medical/surgical problems and multiple concomitant medications. Patients with congestive heart failure requiring pharmacologic management, in particular those with unstable or acute congestive heart failure who are at risk of hypoperfusion and hypoxemia, are at increasedrisk of lactic acidosis. The risk of lactic acidosis increases with the degree of renal dysfunction and the patient's age. The risk of lactic acidosis may, therefore, be significantly decreased by regular monitoring of renal function in patients taking metformin and by use of the minimum effective dose of metformin. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. Metformin treatment should not be initiated in patients���80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced, as these patients are more susceptible to developing lactic acidosis. In addition, metformin should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration or sepsis. Because impaired hepatic function may significantly limit the ability to clear lactate, metformin should generally be avoided in patients with clinical or laboratory evidence of hepatic disease. Patients should be cautioned against excessive alcohol intake, either acute or chronic, when taking metformin hydrochloride tablets, since alcohol potentiates the effects of metformin hydrochloride on lactate metabolism. In addition, metformin should be temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure . The onset of lactic acidosis often is subtle, and accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence and nonspecific abdominal distress. There may be associated hypothermia, hypotension and resistant bradyarrhythmias with more marked acidosis. The patient and the patient's physician must be aware of the possible importance of such symptoms and the patient should be instructed to notify the physician immediately if they occur . Metformin hydrochloride tablets should be withdrawn until the situation is clarified. Serum electrolytes, ketones, blood glucose and, if indicated, blood pH, lactate levels and even blood metformin levels may be useful. Once a patient is stabilized on any dose level of metformin, gastrointestinal symptoms, which are common during initiation of therapy, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease. Levels of fasting venous plasma lactate above the upper limit of normal but less than 5 mmol/L in patients taking metformin do not necessarily indicate impending lactic acidosis and may be explainable by other mechanisms, such as poorly controlled diabetes or obesity, vigorous physical activity or technical problems in sample handling. Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia). Lactic acidosis is a medical emergency that must be treated in a hospital setting. In a patient with lactic acidosis who is taking metformin, the drug should be discontinued immediately and general supportive measures promptly instituted. Because metformin hydrochloride is dialyzable (with a clearance of up to 170 mL/min under good hemodynamic conditions), prompt hemodialysis is recommended to correct the acidosis and remove the accumulated metformin. Such management often results in prompt reversal of symptoms and recovery.
|
| dailymed-drugs:2811 |
Lactic Acidosis: Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with metformin; when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis may also occur in association with a number of pathophysiologic conditions, including diabetes mellitus, and whenever there is significanttissue hypoperfusion and hypoxemia. Lactic acidosis is characterized by elevated blood lactate levels (>5 mmol/L), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. When metformin is implicated as the cause of lactic acidosis, metformin plasma levels>5 mcg/mL are generally found. The reported incidence of lactic acidosis in patients receiving metformin hydrochloride is very low (approximately 0.03 cases/1000 patient-years, with approximately 0.015 fatal cases/1000 patient-years). In more than 20,000 patient-years exposure to metformin in clinical trials, there were no reports of lactic acidosis. Reported cases have occurred primarily in diabetic patients with significant renal insufficiency, including both intrinsic renal disease and renal hypoperfusion, often in the setting of multiple concomitant medical/surgical problems and multiple concomitant medications. Patients with congestive heart failure requiring pharmacologic management, in particular those with unstable or acute congestive heart failure who are at risk of hypoperfusion and hypoxemia, are at increased risk of lactic acidosis. The risk of lactic acidosis increases with the degree of renal dysfunction and the patient's age. The risk of lactic acidosis may, therefore, be significantly decreased by regular monitoring of renal function in patients taking metformin and by use of the minimum effective dose of metformin. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. Metformin treatment should not be initiated in patients���80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced, as these patients are more susceptible to developing lactic acidosis. In addition, metformin should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration or sepsis. Because impaired hepatic function may significantly limit the ability to clear lactate, metformin should generally be avoided in patients with clinical or laboratory evidence of hepatic disease. Patients should be cautioned against excessive alcohol intake, either acute or chronic, when taking metformin hydrochloride tablets, since alcohol potentiates the effects of metformin hydrochloride on lactate metabolism. In addition, metformin should be temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure . The onset of lactic acidosis often is subtle, and accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence and nonspecific abdominal distress. There may be associated hypothermia, hypotension and resistant bradyarrhythmias with more marked acidosis. The patient and the patient's physician must be aware of the possible importance of such symptoms and the patient should be instructed to notify the physician immediately if they occur . Metformin hydrochloride tabletsshould be withdrawn until the situation is clarified. Serum electrolytes, ketones, blood glucose and, if indicated, blood pH, lactate levels, and even blood metformin levels may be useful. Once a patient is stabilized on any dose level of metformin, gastrointestinal symptoms, which are common during initiation of therapy, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease. Levels of fasting venous plasma lactate above the upper limit of normal but less than 5 mmol/L in patients taking metformin do not necessarily indicate impending lactic acidosis and may be explainable by other mechanisms, such as poorly controlled diabetes or obesity, vigorous physical activity or technical problems in sample handling. Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia). Lactic acidosis is a medical emergency that must be treated in a hospital setting. In a patient with lactic acidosis who is taking metformin, the drug should be discontinued immediately and general supportive measures promptly instituted. Because metformin hydrochloride is dialyzable (with a clearance of up to 170 mL/min under good hemodynamic conditions), prompt hemodialysis is recommended to correct the acidosis and remove the accumulated metformin. Such management often results in prompt reversal of symptoms and recovery.
|
| dailymed-drugs:3842 |
Lactic Acidosis:: Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with metformin hydrochloride extended-release tablets; when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis may also occur in association with a number of pathophysiologic conditions, including diabetes mellitus, and whenever there is significant tissue hypoperfusion and hypoxemia. Lactic acidosis is characterized by elevated blood lactate levels (>5 mmol/L), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. When metformin is implicated as the cause of lactic acidosis, metformin plasma levels>5 mcg/mL are generally found. The reported incidence of lactic acidosis in patients receiving metformin hydrochloride is very low (approximately 0.03 cases/1000 patient-years, with approximately 0.015 fatal cases/1000 patient-years). In more than 20,000 patient-years exposure to metformin in clinical trials, there were no reports of lactic acidosis. Reported cases have occurred primarily in diabetic patients with significant renal insufficiency, including both intrinsic renal disease and renal hypoperfusion, often in the setting of multiple concomitant medical/surgical problemsand multiple concomitant medications. Patients with congestive heart failure requiring pharmacologic management, in particular those with unstable or acute congestive heart failure who are at risk of hypoperfusion and hypoxemia, are at increased risk of lactic acidosis. The risk of lactic acidosis increases with the degree of renal dysfunction and the patient's age. The risk of lactic acidosis may, therefore, be significantly decreased by regular monitoring of renal function in patients taking metformin hydrochloride extended-release tablets and by use of the minimum effective dose of metformin hydrochloride extended-release tablets. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. Metformin hydrochloride extended-release tablet treatment should not be initiated in patients���80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced, as these patients are more susceptible to developing lactic acidosis. In addition, metformin hydrochloride extended-release tablets should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration, or sepsis. Because impaired hepatic function may significantly limit the ability to clear lactate, metformin hydrochloride extended-release tablets should generally be avoided in patients with clinical or laboratory evidence of hepatic disease. Patients should be cautioned against excessive alcohol intake, either acute or chronic, when taking metformin hydrochloride extended-release tablets, since alcohol potentiates the effects of metformin hydrochloride on lactate metabolism. In addition, metformin hydrochloride extended-release tablets should be temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure (see also PRECAUTIONS). The onset of lactic acidosis often is subtle, and accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. There may be associated hypothermia, hypotension, and resistant bradyarrhythmias with more marked acidosis. The patient and the patient's physician must be aware of the possible importance of such symptoms and the patient should be instructed to notify the physician immediately if they occur (see also PRECAUTIONS). Metformin hydrochloride extended-release tablets should be withdrawn until the situation is clarified. Serum electrolytes, ketones, blood glucose and, if indicated, blood pH, lactate levels, and even blood metformin levels may be useful. Once a patient is stabilized on any dose level of metformin hydrochloride extended-release tablets, gastrointestinal symptoms, which are common during initiation of therapy, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease. Levels of fasting venous plasma lactate above the upper limit of normal but less than 5 mmol/L in patients taking metformin hydrochloride extended-release tablets do not necessarily indicate impending lactic acidosis and may be explainable by other mechanisms, such as poorly controlled diabetes or obesity, vigorous physical activity, or technical problems in sample handling. (See also PRECAUTIONS.) Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia). Lactic acidosis is a medical emergency that must be treated in a hospital setting. In a patient with lactic acidosis who is taking metformin hydrochloride extended-release tablets, the drug should be discontinued immediately and general supportive measures promptly instituted. Because metformin hydrochloride is dialyzable (with a clearance of up to 170 mL/min under good hemodynamic conditions), prompt hemodialysis is recommended to correct the acidosis and remove the accumulated metformin. Such management often results in prompt reversal of symptoms and recovery. (See also CONTRAINDICATIONS and PRECAUTIONS).
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| dailymed-drugs:3887 |
Lactic Acidosis: Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with metformin; when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis may also occur in association with a number of pathophysiologic conditions, including diabetes mellitus, and whenever there is significant tissue hypoperfusion and hypoxemia. Lactic acidosis is characterized by elevated blood lactate levels (>5 mmol/L), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. When metformin is implicated as the cause of lactic acidosis, metformin plasma levels>5��g/mL are generally found. The reported incidence of lactic acidosis in patients receiving metformin hydrochloride is very low (approximately 0.03 cases/1000 patient-years, with approximately 0.015 fatal cases/1000 patient-years). In more than 20,000 patient-years exposure to metformin in clinical trials, there were no reports of lactic acidosis. Reported cases have occurred primarily in diabetic patients with significant renal insufficiency, including both intrinsic renal disease and renal hypoperfusion, often in the setting of multiple concomitant medical/surgical problems and multiple concomitant medications. Patients with congestive heart failure requiring pharmacologic management, in particular those with unstable or acute congestive heart failure who are at risk of hypoperfusion and hypoxemia are at increased riskof lactic acidosis. The risk of lactic acidosis increases with the degree of renal dysfunction and the patient's age. The risk of lactic acidosis may, therefore, be significantly decreased by regular monitoring of renal function in patients taking metformin and by use of the minimum effective dose of metformin. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. Metformin treatment should not be initiated in patients���80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced, as these patients are more susceptible to developing lactic acidosis. In addition, metformin should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration or sepsis. Because impaired hepatic function may significantly limit the ability to clear lactate, metformin should generally be avoided in patients with clinical or laboratory evidence of hepatic disease. Patients should be cautioned againstexcessive alcohol intake, either acute or chronic, when taking metformin hydrochloride tablets, since alcohol potentiates the effects of metformin hydrochloride on lactate metabolism. In addition, metformin should be temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure . The onset of lactic acidosis often is subtle, and accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence and nonspecific abdominal distress. There may be associated hypothermia, hypotension and resistant bradyarrhythmias with more marked acidosis. The patient and the patient's physician must be aware of the possible importance of such symptoms and the patient should be instructed to notify the physician immediately if they occur . Metformin hydrochloride tablets should be withdrawn until the situation is clarified. Serum electrolytes, ketones, blood glucose and, if indicated, blood pH, lactate levels and even bloodmetformin levels may be useful. Once a patient is stabilized on any dose level of metformin, gastrointestinal symptoms, which are common during initiation of therapy, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease. Levels of fasting venous plasma lactate above the upper limit of normal but less than 5 mmol/L in patients taking metformin do not necessarily indicate impending lactic acidosis and may be explainable by other mechanisms, such as poorly controlled diabetes or obesity, vigorous physical activity or technical problems in sample handling. Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia). Lactic acidosis is a medical emergency that must be treated in a hospital setting. In a patient with lactic acidosis who is taking metformin, the drug should be discontinued immediately and general supportive measures promptly instituted. Because metformin hydrochloride is dialyzable (with a clearance of up to 170 mL/min under good hemodynamic conditions), prompt hemodialysis is recommended to correct the acidosis and remove the accumulated metformin. Such management often results in prompt reversal of symptoms and recovery. .
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| dailymed-drugs:4215 |
Mortality���Flecainide was included in the National Heart Lung and Blood Institute's Cardiac Arrhythmia Suppression Trial (CAST), a long term, multicenter, randomized, double-blind study in patients with asymptomatic non-life-threatening ventricular arrhythmias who had a myocardial infarction more than six days but less than two years previously. An excessive mortality or non-fatal cardiac arrest rate was seen in patients treated with flecainide compared with that seen in patients assigned to a carefully matched placebo-treated group. This rate was 16/315 (5.1%)for flecainide and 7/309 (2.3%) for the matched placebo. The average duration of treatment with flecainide in this study was ten months. The applicability of the CAST results to other populations (e.g., those without recent myocardial infarction) is uncertain, but at present, it is prudent to consider the risks of Class IC agents (including flecainide), coupled with the lack of any evidence of improved survival, generally unacceptable in patients without life-threatening ventricular arrhythmias, even if the patients are experiencing unpleasant, but not life-threatening, symptoms or signs. Ventricular Pro-arrhythmic Effects in Patients with Atrial Fibrillation/Flutter. A review of the world literature revealed reports of 568 patients treated with oral flecainide for paroxysmal atrial fibrillation/flutter (PAF). Ventricular tachycardia was experienced in 0.4% (2/568) of these patients. Of 19 patients in the literature with chronic atrial fibrillation (CAF), 10.5% (2) experienced VT or VF. FLECAINIDE IS NOT RECOMMENDED FOR USE IN PATIENTS WITH CHRONIC ATRIAL FIBRILLATION. Case reports of ventricular proarrhythmic effects in patients treated with flecainide for atrial fibrillation/flutter have included increased PVCs, VT, ventricular fibrillation (VF), and death. As with other Class I agents, patients treated with flecainide for atrial flutter have been reported with 1:1 atrioventricular conduction due to slowing the atrial rate. A paradoxical increase in the ventricular rate also may occur in patients with atrial fibrillation who receive flecainide. Concomitant negative chronotropic therapy such as digoxin or beta-blockers may lower the risk of this complication.
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| dailymed-drugs:1 |
BEFORE THERAPY WITH CEFIZOX IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEFIZOX, OTHER CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS. IF THIS PRODUCT IS TO BE GIVEN TO PENICILLIN��SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE CROSS HYPERSENSITIVITY AMONG BETA���LACTAM ANTIBIOTICS HAS BEEN CLEARLY DOCUMENTED AND MAY OCCUR IN UP TO 10% OF PATIENTS WITH A HISTORY OF PENICILLIN ALLERGY. IF AN ALLERGIC REACTION TO CEFIZOX OCCURS, DISCONTINUE THE DRUG. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE TREATMENT WITH EPINEPHRINE AND OTHER EMERGENCY MEASURES, INCLUDING OXYGEN, IV FLUIDS, IV ANTIHISTAMINES, CORTICOSTEROIDS, PRESSOR AMINES, AND AIRWAY MANAGEMENT, AS CLINICALLY INDICATED. Pseudomembranous colitis has been reported with nearly all antibacterial agents, including ceftizoxime, and may range in severity from mild to life threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents. Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is a primary cause of���antibiotic���associated���colitis. After the diagnosis of pseudomembranous colitis has been established, appropriate therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against Clostridium difficile colitis.
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| dailymed-drugs:2 |
Particular care is needed for patients who are transferred from systemically active corticosteroids to FLOVENT DISKUS because deaths due to adrenal insufficiency have occurred in patients with asthma during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids. After withdrawal from systemic corticosteroids, a number of months are required for recovery of HPA function. Patients who have been previously maintained on 20 mg or more per day of prednisone (or its equivalent) may be most susceptible, particularly when their systemic corticosteroids have been almost completely withdrawn. During this period of HPA suppression, patients may exhibit signs and symptoms of adrenal insufficiency when exposed to trauma, surgery, or infection (particularly gastroenteritis) or other conditions associated with severe electrolyte loss. Although fluticasone propionate inhalation powder may provide control of asthma symptoms during these episodes, in recommended doses it supplies less than normal physiological amounts of corticosteroid systemically and does NOT provide the mineralocorticoid activity that is necessary for coping with these emergencies. During periods of stress or a severe asthma attack, patients who have been withdrawn from systemic corticosteroids should be instructed to resume oral corticosteroids (in large doses) immediately and to contact their physicians for further instruction. These patients should also be instructed to carry a warning card indicating that they may need supplementary systemic corticosteroids during periods of stress or a severe asthma attack. A drug interaction study in healthy subjects has shown that ritonavir (a highly potent cytochrome P450 3A4 inhibitor) can significantly increase plasma fluticasone propionate concentration, resulting in significantly reduced serum cortisol concentrations (see CLINICAL PHARMACOLOGY: Pharmacokinetics: Drug Interactions and PRECAUTIONS: Drug Interactions: Inhibitors of Cytochrome P450). During postmarketing use, there have been reports of clinically significant drug interactions in patients receiving fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects including Cushing syndrome and adrenal suppression. Therefore, coadministration of fluticasone propionate and ritonavir is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects. Patients requiring oral corticosteroids should be weaned slowly from systemic corticosteroid use after transferring to fluticasone propionate inhalation powder. In a clinical trial of 111 patients, prednisone reduction was successfully accomplished by reducing the daily prednisone dose by 2.5 mg on a weekly basis during transfer to inhaled fluticasone propionate. Successive reduction of prednisone dose was allowed only when lung function; symptoms; and as-needed, short-acting beta-agonist use were better than or comparable to that seen before initiation of prednisone dose reduction. Lung function (FEVor AM PEF), beta-agonist use, and asthma symptoms should be carefully monitored during withdrawal of oral corticosteroids. In addition to monitoring asthma signs and symptoms, patients should be observed for signs and symptoms of adrenal insufficiency such as fatigue, lassitude, weakness, nausea and vomiting, and hypotension. Transfer of patients from systemic corticosteroid therapy to FLOVENT DISKUS may unmask conditions previously suppressed by the systemic corticosteroid therapy, e.g., rhinitis, conjunctivitis, eczema, arthritis, and eosinophilic conditions. Persons who are using drugs that suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in susceptible children or adults using corticosteroids. In such children or adults who have not had these diseases or been properly immunized, particular care should betaken to avoid exposure. How the dose, route, and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective package inserts forcomplete VZIG and IG prescribing information.) If chickenpox develops, treatment with antiviral agents may be considered. FLOVENT DISKUS is not to be regarded as a bronchodilator and is not indicated for rapid relief of bronchospasm. As with other inhaled medications, bronchospasm may occur with an immediate increase in wheezing after dosing. If bronchospasm occurs following dosing with FLOVENT DISKUS, it should be treated immediately with a fast-acting inhaled bronchodilator. Treatment with FLOVENT DISKUS should be discontinued and alternative therapy instituted. Patients should be instructed to contact their physicians immediately when episodes of asthma that are not responsive to bronchodilators occur during the course of treatment with FLOVENT DISKUS. During such episodes, patients may require therapy with oral corticosteroids.
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| dailymed-drugs:3 |
Cardiac Failure: Sympathetic stimulation may be a vital component supporting circulatory function in patients with congestive heart failure, and its inhibition by beta blockade may precipitate more severe failure. Although beta blockers should be avoided in overt congestive heart failure, if necessary, they can be used with caution in patients with a history of failure who are well-compensated, usually with digitalis and diuretics. Beta-adrenergic blocking agents do not abolish the inotropic action of digitalis on heart muscle. IN PATIENTS WITHOUT A HISTORY OF HEART FAILURE, continued use of beta blockers can, in some cases, lead to cardiac failure. Therefore, at the first sign or symptom of heart failure, the patient should be digitalized and/or treated with diuretics, and the response observed closely, or nadolol should be discontinued (gradually, if possible).<br/>Exacerbation of Ischemic Heart Disease Following Abrupt Withdrawal: Hypersensitivity to catecholamines has been observed in patients withdrawn from beta-blocker therapy; exacerbation of angina and, in some cases, myocardial infarction have occurred after abrupt discontinuation of such therapy. When discontinuing chronically administered nadolol, particularly in patients with ischemic heart disease, the dosage should be gradually reduced over a period of one to two weeks and the patient should be carefully monitored. Ifangina markedly worsens or acute coronary insufficiency develops, nadolol administration should be reinstituted promptly, at least temporarily, and other measures appropriate for the management of unstable angina should be taken. Patients should be warned against interruption or discontinuation of therapy without the physician's advice. Because coronary artery disease is common and may be unrecognized, it may be prudent not to discontinue nadolol therapy abruptly even in patients treated only for hypertension.<br/>Nonallergic Bronchospasm (e.g., chronic bronchitis, emphysema): PATIENTS WITH BRONCHOSPASTIC DISEASES SHOULD IN GENERAL NOT RECEIVE BETA BLOCKERS. Nadolol should be administered with caution since it may block bronchodilation produced by endogenous or exogenous catecholamine stimulation of betareceptors.<br/>Major Surgery: Because beta blockade impairs the ability of the heart to respond to reflex stimuli and may increase the risks of general anesthesia and surgical procedures, resulting in protracted hypotension or low cardiac output, it has generally been suggested that such therapy should be withdrawn several days prior to surgery. Recognition of the increased sensitivity to catecholamines of patients recently withdrawn from beta-blocker therapy, however, has made this recommendation controversial. If possible, beta blockers should be withdrawn well before surgery takes place. In the event of emergency surgery, the anesthesiologist should be informed that the patient is on beta-blocker therapy. The effects of nadolol can be reversed by administration of beta-receptor agonists such as isoproterenol, dopamine, dobutamine, or norepinephrine. Difficulty in restarting and maintaining the heart beat has also been reported with beta-adrenergic receptor blocking agents.<br/>Diabetes and Hypoglycemia: Beta-adrenergic blockade may prevent the appearance of premonitory signs and symptoms (e.g., tachycardia and blood pressure changes) of acute hypoglycemia. This is especially important with labile diabetics. Beta blockade also reduces the release of insulin in response to hyperglycemia; therefore, it may be necessary to adjust the dose of antidiabetic drugs.<br/>Thyrotoxicosis: Beta-adrenergic blockade may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-adrenergic blockade which might precipitate a thyroid storm.
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| dailymed-drugs:5 |
LOCAL ANESTHETICS SHOULD ONLY BE EMPLOYED BY CLINICIANS WHO ARE WELL VERSED IN DIAGNOSIS AND MANAGEMENT OF DOSE-RELATED TOXICITY AND OTHER ACUTE EMERGENCIES WHICH MIGHT ARISE FROM THE BLOCK TO BE EMPLOYED, AND THEN ONLY AFTER INSURING THE IMMEDIATE AVAILABILITY OF OXYGEN, OTHER RESUSCITATIVE DRUGS, CARDIOPULMONARY RESUSCITATIVE EQUIPMENT, AND THE PERSONNEL RESOURCES NEEDED FOR PROPER MANAGEMENT OF TOXIC REACTIONS AND RELATED EMERGENCIES. DELAY IN PROPER MANAGEMENT OF DOSE-RELATED TOXICITY, UNDERVENTILATION FROM ANY CAUSE, AND/ORALTERED SENSITIVITY MAY LEAD TO THE DEVELOPMENT OF ACIDOSIS, CARDIAC ARREST AND, POSSIBLY, DEATH. Local anesthetic solutions containing antimicrobial preservatives (ie, those supplied in multiple-dose vials) should not be used for epidural or caudal anesthesia because safety has not been established with regard to intrathecal injection, either intentionally or inadvertently, of such preservatives. It is essential that aspiration for blood or cerebrospinal fluid (where applicable) be done prior to injecting any local anesthetic, both the original dose and all subsequent doses, to avoid intravascular or subarachnoid injection. However, a negative aspiration does not ensure against an intravascular or subarachnoid injection. Reactions resulting in fatality have occurred on rare occasions with the use of local anesthetics. Mepivacaine with epinephrine or other vasopressors should not be used concomitantly with ergot-type oxytocic drugs, because a severe persistent hypertension may occur. Likewise, solutions of mepivacaine containing a vasoconstrictor, such as epinephrine, should be used with extreme caution in patients receiving monoamine oxidase inhibitors (MAOI) or antidepressants of the triptyline or imipramine types, because severe prolonged hypertension may result. Local anesthetic procedures should be used with caution when there is inflammation and/or sepsis in the region of the proposed injection. Mixing or the prior or intercurrent use of any local anesthetic with mepivacaine cannot be recommended because of insufficient data on the clinical use of such mixtures
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| dailymed-drugs:6 |
MUSTARGEN(Mechlorethamine HCl) should be administered only under the supervision of a physician who is experienced in the use of cancer chemotherapeutic agents.This drug is HIGHLY TOXIC and both powder and solution must be handled and administered with care. Inhalation of dust or vapors and contact with skin or mucous membranes, especially those of the eyes, must be avoided. Avoid exposure during pregnancy. Due to the toxic properties of mechlorethamine (e.g., corrosivity, carcinogenicity, mutagenicity, teratogenicity), special handling procedures should be reviewed prior to handling and followed diligently.Extravasation of the drug into subcutaneous tissues results in a painful inflammation. The area usually becomes indurated and sloughing may occur. If leakage of drug is obvious, prompt infiltration of the area with sterile isotonic sodium thiosulfate (1/6 molar) and application of an ice compress for 6 to 12 hours may minimize the local reaction. For a 1/6 molar solution of sodium thiosulfate, use 4.14 g of sodium thiosulfate per 100 mL of Sterile Water for Injection or 2.64 gof anhydrous sodium thiosulfate per 100 mL or dilute 4 mL of Sodium Thiosulfate Injection (10%) with 6 mL of Sterile Water for Injection.
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| dailymed-drugs:8 |
Prolonged use of corticosteroids may result in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision, and in posterior subcapsular cataract formation. Prolonged use may also suppress the host immune response and thus increase the hazard of secondary ocular infections. Various ocular diseases and long-term use of topical corticosteroids have been known to cause corneal and scleral thinning. Use of topical corticosteroids in the presence of thin corneal or scleral tissue may lead to perforation. Acute purulent infections of the eye may be masked or activity enhanced by the presence of corticosteroid medication. If this product is used for 10 days or longer, intraocular pressure should be routinely monitored even though it may be difficult in children and uncooperative patients. Steroids should be used with caution in the presence of glaucoma. Intraocular pressure should be checked frequently. The use of steroids after cataract surgery may delay healing and increase the incidence of bleb formation. Use of ocular steroids may prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex). Employment of a corticosteroid medication in the treatment of patients with a history of herpes simplex requires great caution; frequent slit lamp microscopy is recommended. Corticosteroids are not effective in mustard gas keratitis and Sj��gren's keratoconjunctivitis. Contains sodium bisulfite, a sulfite that may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.
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| dailymed-drugs:1230 |
Prolonged use of corticosteroids may result in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision, and in posterior subcapsular cataract formation. Prolonged use may also suppress the host immune response and thus increase the hazard of secondary ocular infections. Various ocular diseases and long-term use of topical corticosteroids have been known to cause corneal and scleral thinning. Use of topical corticosteroids in the presence of thin corneal or scleral tissue may lead to perforation. Acute purulent infections of the eye may be masked or activity enhanced by the presence of corticosteroid medication. If this product is used for 10 days or longer, intraocular pressure should be routinely monitored even though it may be difficult in children and uncooperative patients. Steroids should be used with caution in the presence of glaucoma. Intraocular pressure should be checked frequently. The use of steroids after cataract surgery may delay healing and increase the incidence of bleb formation. Use of ocular steroids may prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex). Employment of a corticosteroid medication in the treatment of patients with a history of herpes simplex requires great caution; frequent slit lamp microscopy is recommended. Corticosteroids are not effective in mustard gas keratitis and Sj��gren's keratoconjunctivitis. Contains sodium bisulfite, a sulfite that may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.
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| dailymed-drugs:10 |
As with other topically applied ophthalmic drugs, Betimol is absorbed systemically. The same adverse reactions found with systemic administration of beta-adrenergic blocking agents may occur with topical administration. For example, severe respiratory and cardiac reactions, including death due to bronchospasm in patients with asthma, and rarely, death in association with cardiac failure have been reported following systemic or topical administration of beta-adrenergic blocking agents. Cardiac Failure: Sympathetic stimulation may be essential for support of the circulation in individuals with diminished myocardial contractility, and its inhibition by beta-adrenergic receptor blockade may precipitate more severe cardiac failure. In patients without a history of cardiac failure, continued depression of the myocardium with beta-blocking agents over a period of time can, in some cases, lead to cardiac failure. Betimol should be discontinued at the first sign or symptom of cardiac failure. Obstructive Pulmonary Disease: Patients with chronic obstructive pulmonary disease (e.g. chronic bronchitis, emphysema) of mild or moderate severity, bronchospastic disease, or a history of bronchospastic disease (other than bronchial asthma or a history of bronchial asthma which are contraindications) should in general not receive beta-blocking agents. Major Surgery: The necessity or desirability of withdrawal of beta-adrenergic blocking agents prior to a major surgery is controversial. Beta-adrenergic receptor blockade impairs the ability of the heart to respond to beta-adrenergically mediated reflex stimuli. This may augment the risk of general anesthesia in surgical procedures. Some patients receiving beta-adrenergic receptor blocking agents have been subject to protracted severe hypotension during anesthesia. Difficulty in restarting and maintaining the heartbeat has also been reported. For these reasons, in patients undergoing elective surgery, gradual withdrawal of beta-adrenergic receptor blocking agents is recommended. If necessary during surgery, the effects of beta-adrenergic blocking agents may be reversed by sufficient doses of beta-adrenergic agonists. Diabetes Mellitus: Beta-adrenergic blocking agents should be administered with caution in patients subject to spontaneous hypoglycemia or to diabetic patients (especially those with labile diabetes) who are receiving insulin or oral hypoglycemic agents. Beta-adrenergic receptor blocking agents may mask the signs and symptoms of acute hypoglycemia. Thyrotoxicosis: Beta-adrenergic blocking agents may mask certain clinical signs (e.g. tachycardia) of hyperthyroidism. Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-adrenergic blocking agents which might precipitate a thyroid storm.
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| dailymed-drugs:11 |
Keep out of reach of pediatric patients. CHEMET is not a substitute for effective abatement of lead exposure. Mild to moderate neutropenia has been observed in some patients receiving succimer. While a causal relationship to succimer has not been definitely established, neutropenia has been reported with other drugs in the same chemical class. A complete blood count with white blood cell differential and direct platelet counts should be obtained prior to and weekly during treatment with succimer. Therapy should either be withheld or discontinued if the absolute neutrophil count (ANC) is below1200/��L and the patient followed closely to document recovery of the ANC to above 1500/��L or to the patient's baseline neutrophil count. There is limited experience with reexposure in patients who have developed neutropenia. Therefore, such patients should be rechallenged only if the benefit of succimer therapy clearly outweighs the potential risk of another episode of neutropenia and then only with careful patient monitoring. Patients treated with succimer should be instructed to promptly report any signs of infection. If infection is suspected, the above laboratory tests should be conducted immediately.
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| dailymed-drugs:12 |
Clinical Worsening and Suicide
Risk: Patients with major
depressive disorder (MDD), both adult and pediatric, may experience worsening of
their depression and/or the emergence of suicidal ideation and behavior
(suicidality) or unusual changes in behavior, whether or not they are taking
antidepressant medications, and this risk may persist until significant remission
occurs. Suicide is a known risk of depression and certain other psychiatric
disorders, and these disorders themselves are the strongest predictors of suicide.
There has been a long-standing concern, however, that antidepressants may have a
role in inducing worsening of depression and the emergence of suicidality in
certain patients during the early phases of treatment. Pooled analyses of
short-term placebo-controlled trials of antidepressant drugs (SSRIs and others)
showed that these drugs increase the risk ofsuicidal thinking and behavior
(suicidality) in children, adolescents, and young adults (ages 18-24) with major
depressive disorder (MDD) and other psychiatric disorders. Short-term studies did
not show an increase in the risk of suicidality with antidepressants compared to
placebo in adults beyond age 24; there was a reduction with antidepressants
compared to placebo in adults aged 65 and older. The pooled analyses of
placebo-controlled trials in children and adolescents with MDD, obsessive
compulsive disorder (OCD), or other psychiatric disorders included a total of 24
short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled
analyses of placebo-controlled trials in adults with MDD or other psychiatric
disorders included a total of 295 short-term trials (median duration of 2 months)
of 11 antidepressant drugs in over 77,000 patients. There was considerable
variation in risk of suicidality among drugs, but a tendency toward an increase in
the younger patients for almost all drugs studied. There were differences in
absolute risk of suicidality across different indications, with the highest
incidence in MDD. The risk differences (drug vs placebo), however, were relatively
stable within age strata and across indications. These risk differences
(drug-placebo difference in the number of cases of suicidality per 1000 patients
treated) are provided in Table 1. No suicides occurred in
any of the pediatric trials. There were suicides in the adult trials, but the
number was not sufficient to reach any conclusion about drug effect on suicide. It is unknown whether the
suicidality risk extends to longer-term use, i.e., beyond several months. However,
there is substantial evidence from placebo-controlled maintenance trials in adults
with depression that the use of antidepressants can delay the recurrence of
depression. All patients being treated with antidepressants for any
indication should be monitored appropriately and observed closely for clinical
worsening, suicidality, and unusual changes in behavior, especially during the
initial few months of a course of drug therapy, or at times of dose changes,
either increases or decreases. The following symptoms,
anxiety, agitation, panic attacks, insomnia, irritability, hostility,
aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and
mania, have been reported in adult and pediatric patients being treated with
antidepressants for major depressive disorder as well as for other indications,
both psychiatric and nonpsychiatric. Although a causal link between the emergence
of such symptoms and either the worsening of depression and/or the emergence of
suicidal impulses has not been established, there is concern that such symptoms
may represent precursors to emerging suicidality. Consideration should be
given to changing the therapeutic regimen, including possibly discontinuing the
medication, in patients whose depression is persistently worse, or who are
experiencing emergent suicidality or symptoms that might be precursors to
worsening depression or suicidality, especially if these symptoms are severe,
abrupt in onset, or were not part of the patient's presenting symptoms. Families and caregivers of patients being treated with
antidepressants for major depressive disorder or other indications, both
psychiatric and nonpsychiatric, should be alerted about the need to monitor
patients for the emergence of agitation, irritability, unusual changes in
behavior, and the other symptoms described above, as well as the emergence of
suicidality, and to report such symptoms immediately to health care providers.
Such monitoring should include daily observation by families and caregivers.
Prescriptions for REMERON' (mirtazapine) Tablets should be written for
the smallest quantity of tablets consistent with good patient management, in orderto reduce the risk of overdose. Screening Patients for Bipolar Disorder: A
major depressive episode may be the initial presentation of bipolar disorder. It
is generally believed (though not established in controlled trials) that treating
such an episode with an antidepressant alone may increase the likelihood of
precipitation of a mixed/manic episode in patients at risk for bipolar disorder.
Whether any of the symptoms described above represent such a conversion is
unknown. However, prior to initiating treatment with an antidepressant, patients
with depressive symptoms should be adequately screened to determine if they are at
risk for bipolar disorder; such screening should include a detailed psychiatric
history, including a family history of suicide, bipolar disorder, and depression.
It should be noted that REMERON' (mirtazapine) Tablets are not approved for use in
treating bipolar depression.<br/>Agranulocytosis: In premarketing clinical trials, two (one with Sj��gren's
Syndrome) out of 2796 patients treated with REMERON' (mirtazapine) Tablets
developed agranulocytosis [absolute neutrophil count (ANC)<500/mmwith associated signs and symptoms, e.g., fever, infection,
etc.] and a third patient developed severe neutropenia (ANC<500/mmwithout any associated symptoms). For these three patients,
onset of severe neutropenia was detected on days 61, 9, and 14 of treatment,
respectively. All three patients recovered after REMERON' was stopped. These
three cases yield a crude incidence of severe neutropenia (with or without
associated infection) of approximately 1.1 per thousand patients exposed, with a
very wide 95% confidence interval, i.e., 2.2 cases per 10,000 to 3.1 cases per
1000. If a patient develops a sore throat, fever, stomatitis or other signs of
infection, along with a low WBC count, treatment with REMERON' should be
discontinued and the patient should be closely monitored.<br/>MAO Inhibitors: In patients receiving other drugs for major depressive
disorder in combination with a monoamine oxidase inhibitor (MAOI) and in
patients who have recently discontinued a drug for major depressive disorder and
then are started on an MAOI, there have been reports of serious and sometimes
fatal reactions, e.g., including nausea, vomiting, flushing, dizziness, tremor,
myoclonus, rigidity, diaphoresis, hyperthermia, autonomic instability with rapid
fluctuations of vital signs, seizures, and mental status changes ranging from
agitation to coma. Although there are no human data pertinent to such an
interaction with REMERON' (mirtazapine) Tablets, it is recommended that REMERON'
not be used in combination with an MAOI, or within 14 days of initiating or
discontinuing therapy with an MAOI.
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| dailymed-drugs:14 |
ORALLY AND PARENTERALLY ADMINISTERED CLINDAMYCIN HAS BEEN ASSOCIATED WITH SEVERE COLITIS WHICH MAY RESULT IN PATIENT DEATH. USE OF THE TOPICAL FORMULATION OF CLINDAMYCIN RESULTS IN ABSORPTION OF THE ANTIBIOTIC FROM THE SKIN SURFACE. DIARRHEA, BLOODY DIARRHEA, AND COLITIS (INCLUDING PSEUDOMEMBRANOUS COLITIS) HAVE BEEN REPORTED WITH THE USE OF TOPICAL AND SYSTEMIC CLINDAMYCIN. STUDIES INDICATE A TOXIN(S) PRODUCED BY CLOSTRIDIA IS ONE PRIMARY CAUSE OF ANTIBIOTIC-ASSOCIATED COLITIS. THE COLITIS IS USUALLY CHARACTERIZEDBY SEVERE PERSISTENT DIARRHEA AND SEVERE ABDOMINAL CRAMPS AND MAY BE ASSOCIATED WITH THE PASSAGE OF BLOOD AND MUCUS. ENDOSCOPIC EXAMINATION MAY REVEAL PSEUDOMEMBRANOUS COLITIS. STOOL CULTURE FOR Clostridium Difficile AND STOOL ASSAY FOR C. difficile TOXIN MAY BE HELPFUL DIAGNOSTICALLY. WHEN SIGNIFICANT DIARRHEA OCCURS, THE DRUG SHOULD BE DISCONTINUED. LARGE BOWEL ENDOSCOPY SHOULD BE CONSIDERED TO ESTABLISH A DEFINITIVE DIAGNOSIS IN CASES OF SEVERE DIARRHEA. ANTIPERISTALTIC AGENTS SUCH AS OPIATES AND DIPHENOXYLATE WITH ATROPINE MAY PROLONG AND/OR WORSEN THE CONDITION. DIARRHEA, COLITIS, AND PSEUDOMEMBRANOUS COLITIS HAVE BEEN OBSERVED TO BEGIN UP TO SEVERAL WEEKS FOLLOWING CESSATION OF ORAL AND PARENTERAL THERAPY WITH CLINDAMYCIN. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation and treatment with an antibacterial drug clinically effective against C. difficile colitis.
|
| dailymed-drugs:15 |
WARNING: NOT FOR INTRAVENOUS
USE. DO NOT INJECT INTRAVENOUSLY OR ADMIX WITH OTHER INTRAVENOUS SOLUTIONS.
THERE HAVE BEEN REPORTS OF INADVERTENT INTRAVENOUS ADMINISTRATION
OF PENCILLIN G BENZATHINE WHICH HAS BEEN ASSOCIATED WITH CARDIORESPIRATORY
ARREST AND DEATH. Prior to administration of this drug, carefully
read the WARNINGS, ADVERSE REACTIONS, and DOSAGE AND ADMINISTRATION sections of the labeling. Penicillin G benzathine should only be prescribed
for the indications listed in this insert.<br/>Anaphylaxis: SERIOUS AND OCCASIONALLY FATAL HYPERSENSITIVITY (ANAPHYLACTIC)
REACTIONS HAVE BEEN REPORTED IN PATIENTS ON PENICILLIN THERAPY. THESE
REACTIONS ARE MORE LIKELY TO OCCUR IN INDIVIDUALS WITH A HISTORY OF
PENICILLIN HYPERSENSITIVITY AND/OR A HISTORY OF SENSITIVITY TO MULTIPLE
ALLERGENS. THERE HAVE BEEN REPORTS OF INDIVIDUALS WITH A HISTORY OF
PENICILLIN HYPERSENSITIVITY WHO HAVE EXPERIENCED SEVERE REACTIONS
WHEN TREATED WITH CEPHALOSPORINS. BEFORE INITIATING THERAPY WITH BICILLIN
L-A, CAREFUL INQUIRY SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY
REACTIONS TO PENICILLINS, CEPHALOSPORINS, OR OTHER ALLERGENS. IF AN
ALLERGIC REACTION OCCURS, BICILLIN L-A SHOULD BE DISCONTINUED AND
APPROPRIATE THERAPY INSTITUTED. SERIOUS
ANAPHYLACTIC REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH
EPINEPHRINE. OXYGEN, INTRAVENOUS STEROIDS AND AIRWAY MANAGEMENT, INCLUDING
INTUBATION, SHOULD ALSO BE ADMINISTERED AS INDICATED. Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly
all antibacterial agents, including Bicillin L-A, and may range in
severity from mild diarrhea to fatal colitis. Treatment with antibacterial
agents alters the normal flora of the colon leading to overgrowth
of C. difficile. C. difficile produces
toxins A and B which contribute to the development of CDAD. Hypertoxin
producing strains of C. difficile cause increased morbidity and mortality, as these infections can
be refractory to antimicrobial therapy and may require colectomy.
CDAD must be considered in all patients who present with diarrhea
following antibacterial use. Careful medical history is necessary
since CDAD has been reported to occur over two months after the administration
of antibacterial agents. If CDAD is suspected
or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued.
Appropriate fluid and electrolyte management, protein supplementation,
antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.<br/>Method of Administration: Do not inject into or near
an artery or nerve. Injection into or near a nerve may result in permanent
neurological damage. Inadvertent intravascular
administration, including inadvertent direct intra-arterial injection
or injection immediately adjacent to arteries, of Bicillin L-A and
other penicillin preparations has resulted in severe neurovascular
damage, including transverse myelitis with permanent paralysis, gangrene
requiring amputation of digits and more proximal portions of extremities,
and necrosis and sloughing at and surrounding the injection site.
Such severe effects have been reported following injections into the
buttock, thigh, and deltoid areas. Other serious complications of
suspected intravascular administration which have been reported include
immediate pallor, mottling, or cyanosis of the extremity both distal
and proximal to the injection site, followed by bleb formation; severe
edema requiring anterior and/or posterior compartment fasciotomy in
the lower extremity. The above-described severe effects and complications
have most often occurred in infants and small children. Prompt consultation
withan appropriate specialist is indicated if any evidence of compromise
of the blood supply occurs at, proximal to, or distal to the site
of injection. Do not inject intravenously or admix with other intravenous solutions.
There have been reports of inadvertent intravenous administration
of penicillin G benzathine which has been associated with cardiorespiratory
arrest and death. Quadriceps femoris fibrosis and atrophy have been reported
following repeated intramuscular injections of penicillin preparations
into the anterolateral thigh.
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| dailymed-drugs:16 |
Potassium Chloride
in 5% Dextrose and Sodium Chloride Injection, USP should be used with
great care, if at all, in patients with congestive heart failure, severe
renal insufficiency, and in clinical states in which there exists edema
with sodium retention. Potassium Chloride
in 5% Dextrose and Sodium Chloride Injection, USP should be used with
great care, if at all, in patients with hyperkalemia, severe renal
failure, and in conditions in which potassium retention is present. Injections
containing carbohydrates with low electrolyte concentration should not
be administered simultaneously with blood through the same
administration set because of the possibility of pseudoagglutination or
hemolysis. The container label for these injections bears the statement:
Do not administer simultaneously with blood. The intravenous
administration of Potassium Chloride in 5% Dextrose and Sodium Chloride
Injection, USP can cause fluid and/or solute overloading resulting in
dilution of serum electrolyte concentrations, overhydration, congested states or pulmonary edema. The risk of dilutional states is inversely
proportional to the electrolyte concentrations of the injection. The
risk of solute overload causing congested states with peripheral and
pulmonary edema is directly proportional to the electrolyte
concentrations of the injection. In patients with
diminished renal function, administration of Potassium Chloride in 5%
Dextrose and Sodium Chloride Injection, USP may result in sodium or
potassium retention. In very low birth
weight infants, excessive or rapid administration of dextrose injection
may result in increased serum osmolality and possible intracerebral
hemorrhage. Potassium salts
should never be administered by IV push.
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| dailymed-drugs:17 |
Deaths: Deaths have been reported from overdose with Amantadine Hydrochloride. The lowest reported acute lethal dose was 1 gram. Acute toxicity may be attributable to the anticholinergic effects of amantadine. Drug overdose has resulted in cardiac, respiratory, renal or central nervous system toxicity. Cardiac dysfunction includes arrhythmia, tachycardia and hypertension .<br/>Suicide Attempts: Suicide attempts, some of which have been fatal, have been reported in patients treated with Amantadine Hydrochloride, many of whom received short courses for influenza treatment or prophylaxis. The incidence of suicide attempts is not known and the pathophysiologic mechanism is not understood. Suicide attempts and suicidal ideation have been reported in patients with and without prior history of psychiatric illness. Amantadine Hydrochloride can exacerbate mental problems in patients with a history of psychiatric disorders or substance abuse. Patients who attempt suicide may exhibit abnormal mental states which include disorientation, confusion, depression, personality changes, agitation, aggressive behavior, hallucinations, paranoia, other psychotic reactions and somnolence or insomnia. Because of the possibility of serious adverse effects, caution should be observed when prescribing Amantadine Hydrochloride to patients being treated with drugs having CNS effects, or for whom the potential risks outweigh the benefit of treatment.<br/>CNS Effects: Patients with a history of epilepsy or other���seizures���should be observed closely for possible increased seizure activity. Patients receiving Amantadine Hydrochloride who note central nervous system effects or blurring of vision should be cautioned against driving or working in situations where alertness and adequate motor coordination are important.<br/>Other: Patients with a history of congestive heart failure or peripheral edema should be followed closely as there are patients who developed congestive heart failure while receiving Amantadine Hydrochloride. Patients with Parkinson's disease improving on Amantadine Hydrochloride should resume normal activities gradually and cautiously, consistent with other medical considerations, such as the presence of osteoporosis or phlebothrombosis. Because Amantadine Hydrochloride has anticholinergic effects and may cause mydriasis, it should not be given to patients with untreated angle closure glaucoma.
|
| dailymed-drugs:19 |
Penicillin G procaine should only be prescribed for the indications
listed in this insert. NOTE: This drug is no longer
indicated in the treatment of gonorrhea.<br/>Anaphylaxis: SERIOUS AND OCCASIONALLY FATAL HYPERSENSITIVITY (ANAPHYLACTIC)
REACTIONS HAVE BEEN REPORTED IN PATIENTS ON PENICILLIN THERAPY. THESE REACTIONS
ARE MORE LIKELY TO OCCUR IN INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY
AND/OR A HISTORY OF SENSITIVITY TO MULTIPLE ALLERGENS. THERE HAVE BEEN REPORTS
OF INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY WHO HAVE EXPERIENCED
SEVERE REACTIONS WHEN TREATED WITH CEPHALOSPORINS. BEFORE INITIATING THERAPY
WITH ANY PENICILLIN, CAREFUL INQUIRY SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY
REACTIONS TO PENICILLINS, CEPHALOSPORINS, OR OTHER ALLERGENS.IF AN ALLERGIC
REACTION OCCURS, THE DRUG SHOULD BE DISCONTINUED AND APPROPRIATE THERAPY INSTITUTED. SERIOUS ANAPHYLACTIC REACTIONS REQUIRE IMMEDIATE EMERGENCY
TREATMENT WITH EPINEPHRINE. OXYGEN, INTRAVENOUS STEROIDS, AND AIRWAY MANAGEMENT,
INCLUDING INTUBATION, SHOULD ALSO BE ADMINISTERED AS INDICATED.<br/>Pseudomembranous Colitis: Pseudomembranous colitis has been
reported with nearly all antibacterial agents, including penicillin G, and
may range in severity from mild to life-threatening. Therefore, it is important
to consider this diagnosis in patients who present with diarrhea subsequent
to the administration of antibacterial agents. Treatment
with antibacterial agents alters the normal flora of the colon and may permit
overgrowth of clostridium. Studies indicate that a toxin produced by Clostridium difficile is one primary cause of���antibiotic-associated colitis.��� After
the diagnosis of pseudomembranous colitis has been established, therapeutic
measures should be initiated. Mild cases of pseudomembranous colitis usually
respond to drug discontinuation alone. In moderate to severe cases, consideration
should be given to management of fluids and electrolytes, protein supplementation
and treatment with an antibacterial drug clinically effective against C. difficile colitis.<br/>Procaine Reactions: Immediate toxic reactions to procaine
may occur in some individuals, particularly when a large single dose is administered
(4.8 million units). These reactions may be manifested by mental disturbances,
including anxiety, confusion, agitation, depression, weakness, seizures, hallucinations,
combativeness, and expressed���fear of impending death.���The
reactions noted in carefully controlled studies occurred in approximately
one in 500 patients who received large doses of penicillin G procaine. Reactions
are transient, lasting from 15 to 30 minutes.<br/>Method of Administration: Do not inject into or near an artery
or nerve. Injection
into or near a nerve may result in permanent neurological damage. Inadvertent
intravascular administration, including inadvertent direct intra-arterial
injection or injection immediately adjacent to arteries, of Penicillin G Procaine
Injectable Suspension and other penicillin preparations has resulted in severe
neurovascular damage, including transverse myelitis with permanent paralysis,
gangrene requiring amputation of digits and more proximal portions of extremities,
and necrosis and sloughing at and surrounding the injection site. Such severe
effects have been reported following injections into the buttock, thigh, and
deltoid areas. Other serious complications of suspected intravascular administration
which have been reported include immediate pallor, mottling, or cyanosis of
the extremity, both distal and proximal to the injection site, followed by
bleb formation; severe edema requiring anterior and/or posterior compartment
fasciotomy in the lower extremity. The above-described severe effects and
complications have most often occurred in infants and small children. Prompt
consultation with an appropriate specialist is indicated if any evidence of
compromise of the blood supply occurs at, proximal to, or distal to the site
of injection.(See PRECAUTIONS, and DOSAGE AND
ADMINISTRATION.) Quadriceps femoris
fibrosis and atrophy have been reported following repeated intramuscular injections
of penicillin preparations into the anterolateral thigh.
|
| dailymed-drugs:20 |
Anaphylactoid and Possibly Related Reactions: Presumably because angiotensin-converting inhibitors affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin, patients receiving ACE inhibitors (including quinapril hydrochloride) may be subject to a variety of adverse reactions, some of them serious.<br/>Head and Neck Angioedema:: Angioedema of the face, extremities, lips, tongue, glottis, and larynx has been reported in patients treated with ACE inhibitors and has been seen in 0.1% of patients receiving quinapril hydrochloride. In two similarly sized U.S. postmarketing trials that, combined, enrolled over 3,000 black patients and over 19,000 non-blacks, angioedema was reported in 0.30% and 0.55% of blacks (in study 1 and 2 respectively) and 0.39% and 0.17% of non-blacks. Angioedema associated with laryngeal edema can be fatal. If laryngeal stridor or angioedema of the face, tongue, or glottis occurs, treatment with quinapril hydrochloride should be discontinued immediately, the patient treated in accordance with accepted medical care, and carefully observed until the swelling disappears. In instances where swelling is confined to the face and lips, the condition generally resolves without treatment; antihistamines may be useful in relieving symptoms. Where there is involvement of the tongue, glottis, or larynx likely to cause airway obstruction, emergency therapy including, but not limited to, subcutaneous epinephrine solution 1:1000 (0.3 to 0.5 mL) should be promptly administered (see ADVERSE REACTIONS).<br/>Intestinal Angioedema:: Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by proceduresincluding abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.<br/>Patients with a history of angioedema:: Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor (see also CONTRAINDICATIONS).<br/>Anaphylactoid reactions during desensitization:: Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions. In the same patients, these reactions were avoided when ACE inhibitors were temporarily withheld, but they reappeared upon inadvertent rechallenge.<br/>Anaphylactoid reactions during membrane exposure:: Anaphylactoid reactions have been reported in patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption.<br/>Hepatic Failure:: Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up.<br/>Hypotension:: Excessive hypotension is rare in patients with uncomplicated hypertension treated with quinapril hydrochloride alone. Patients with heart failure given quinapril hydrochloride commonly have some reduction in blood pressure, but discontinuation of therapy because of continuing symptomatic hypotension usually is not necessary when dosing instructions are followed. Caution should be observed when initiating therapy in patients with heart failure. In controlled studies, syncope was observed in 0.4% of patients (N=3203); this incidence was similar to that observed for captopril (1%) and enalapril (0.8%). Patients at risk of excessive hypotension, sometimes associated with oliguria and/or progressive azotemia, and rarely with acute renal failure and/or death, include patients with the following conditions or characteristics: heart failure, hyponatremia, high dose diuretic therapy, recent intensive diuresis or increase in diuretic dose, renal dialysis, or severe volume and/or salt depletion of any etiology. It may be advisable to eliminate the diuretic (except in patients with heart failure), reduce the diuretic dose or cautiously increase salt intake (except in patients with heart failure) before initiating therapy with quinapril hydrochloride in patients at risk for excessive hypotensionwho are able to tolerate such adjustments. In patients at risk of excessive hypotension, therapy with quinapril hydrochloride should be started under close medical supervision. Such patients should be followed closely for the first two weeks of treatment and whenever the dose of quinapril hydrochloride and/or diuretic is increased. Similar considerations may apply to patients with ischemic heart or cerebrovascular disease in whom an excessive fall in blood pressure could result in amyocardial infarction or a cerebrovascular accident. If excessive hypotension occurs, the patient should be placed in the supine position and, if necessary, receive an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further doses of quinapril hydrochloride, which usually can be given without difficulty once the blood pressure has stabilized. If symptomatic hypotension develops, a dose reduction or discontinuation of quinapril hydrochloride or concomitant diuretic may be necessary.<br/>Neutropenia/Agranulocytosis:: Another ACE inhibitor, captopril, has been shown to cause agranulocytosis and bone marrow depression rarely in patients with uncomplicated hypertension, but more frequently in patients with renal impairment, especially if they also have a collagen vascular disease, such as systemic lupus erythematosus or scleroderma. Agranulocytosis did occur during quinapril hydrochloride treatment in one patient with a history of neutropenia during previous captopril therapy. Available data from clinical trials of quinapril hydrochloride are insufficient to show that, in patients without prior reactions to otherACE inhibitors, quinapril hydrochloride does not cause agranulocytosis at similar rates. As with other ACE inhibitors, periodic monitoring of white blood cell counts in patients with collagen vascular disease and/or renal disease should be considered.<br/>Fetal/Neonatal Morbidity and Mortality:: ACE inhibitors can cause fetal and neonatal morbidity and death when administered to pregnant women. Several dozen cases have been reported in the world literature. When pregnancy is detected, ACE inhibitors should be discontinued as soon as possible. The use of ACE inhibitors during the second and third trimesters of pregnancy has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death. Oligohydramnios has also been reported, presumably resulting from decreased fetal renal function; oligohydramnios in this setting has been associated with fetal limb contractures, craniofacial deformation, and hypoplastic lung development. Prematurity, intrauterine growth retardation, and patent ductus arteriosus have also been reported, although it is not clear whether these occurrences were due to the ACE inhibitor exposure. These adverse effects do not appear to have resulted from intrauterine ACE inhibitor exposure that has been limited to the first trimester. Mothers whose embryos and fetuses are exposed to ACE inhibitors only during the first trimester should be so informed. Nonetheless, when patients become pregnant, physicians should make every effort to discontinue the use of quinapril hydrochloride as soon as possible. Rarely (probably less often than once in every thousand pregnancies), no alternative to ACE inhibitors will be found. In these rare cases, the mother should be apprised of the potential hazards to their fetuses, and serial ultrasound examinations should be performed to assess the intraamniotic environment. If oligohydramnios is observed, quinapril hydrochloride should be discontinued unless it is considered life-saving for the mother. Contraction stress testing (CST), a non-stress test (NST), or biophysical profiling (BPP) may be appropriate, depending upon the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Infants with histories of in utero exposure to ACE inhibitors should be closely observed for hypotension, oliguria, and hyperkalemia. If oliguria occurs, attention should be directed toward support of blood pressure and renal perfusion. Exchange transfusion or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function. Removal of quinapril hydrochloride, which crosses the placenta, from the neonatal circulation is not significantly accelerated by these means. No teratogenic effects of quinapril hydrochloride were seen in studies of pregnant rats and rabbits. On a mg/kg basis, the doses used were up to 180 times (in rats) and one time (in rabbits) the maximum recommended human dose.
|
| dailymed-drugs:21 |
NOT FOR INJECTION���FOR OPHTHALMIC USE ONLY.
|
| dailymed-drugs:22 |
The administration of intravenous solutions can cause fluid and/or solute overload resulting in dilution of serum electrolyte concentrations, overhydration, congested states or pulmonary edema. The risk of dilutional states is inversely proportional to the electrolyte concentration. The risk of solute overload causing congested states with peripheral and pulmonary edema is directly proportional to the electrolyteconcentration. Solutions containing sodium ions should be used with great care, if at all, in patients with congestive heart failure, severe renal insufficiency, and in clinical states in which there is sodium retention with edema. Solutions containing potassium ions should be used with great care, if at all, in patients with hyperkalemia, severe renal failure, and in conditions in which potassium retention is present. In patients with diminished renal function, administration of solutions containing sodium or potassium ions may result in sodium or potassium retention. Solutions containing calcium ions should not be administered through the same administration set as blood because of the likelihood of coagulation.
|
| dailymed-drugs:23 |
Cigarette smoking increases the risk
of serious cardiovascular side effects from combination oral
contraceptive use. This risk increases with age and with
heavy smoking (15 or more cigarettes per day) and is quite
marked in women over 35 years of age. Women who use
combination hormonal contraceptives, including NuvaRing',
should be strongly advised not to smoke. NuvaRing'
and other contraceptives that contain both an estrogen and a
progestin are called combination hormonal contraceptives. There
is no epidemiologic data available to determine whether safety
and efficacy with the vaginal route of administration of
combination hormonal contraceptives would be different than the
oral route. The use of
oral contraceptives is associated with increased risks of
several serious conditions including venous and arterial
thrombotic and thromboembolic events (such as myocardial
infarction, thromboembolism, and stroke), hepatic neoplasia,
gallbladder disease, and hypertension, although the risk of
serious morbidity or mortality is very small in healthy women
without underlying risk factors. The risk of morbidity and
mortality increases significantly in the presence of other
underlying risk factors such as certain inherited
thrombophilias, hypertension, hyperlipidemias, obesity, and
diabetes. The
information contained in this package insert is principally
based on studies carried out in women who used oral
contraceptives with formulations of higher doses of estrogens
and progestogens than those in common use today. The effect of
long-term use of oral contraceptives with lower doses of both
estrogens and progestogens remains to be determined. Throughout
this labeling, epidemiologic studies reported are of two types:
retrospective or case control studies and prospective or cohort
studies. Case control studies provide a measure of the relative
risk of a disease, namely, a
ratio of the incidence of a disease among oral
contraceptive users to that among non-users. The relative risk
does not provide information on the actual clinical occurrence
of a disease. Cohort studies provide a measure of attributable
risk, which is the difference in the incidence of disease between oral
contraceptive users and non-users. The attributable risk does
provide information about the actual occurrence of a disease in
the population. For further information, the reader is referred
to a text on epidemiologic methods.<br/>1. THROMBOEMBOLIC
DISORDERS AND OTHER VASCULAR PROBLEMS:<br/>a.
Thromboembolism: An
increased risk of thromboembolic and thrombotic disease
associated with the use of oral contraceptives is well
established. Case control studies have found the
relative risk of users compared to non-users to be three
for the first episode of superficial venous thrombosis,
four to 11 for deep vein thrombosis or pulmonary
embolism, and 1.5 to six for women with predisposing
conditions for venous thromboembolic disease. Cohort
studies have shown the relative risk to be somewhat
lower, about three for new cases and about 4.5 for new
cases requiring hospitalization. The risk of
thromboembolic disease associated with oral
contraceptives is not related to length of use and
disappears afterpill use is stopped. Several epidemiology studies indicate that third
generation oral contraceptives, including those
containing desogestrel (etonogestrel, the progestin in
NuvaRing', is the biologically active metabolite of
desogestrel), are associated with a higher risk of
venous thromboembolism than certain second generation
oral contraceptives. In general, these studies indicate
an approximate two-fold increased risk, which
correspondsto an additional one to two cases of venous
thromboembolism per 10,000 women-years of use. However,
data from additional studies have not shown this
two-fold increase in risk. It is unknown if NuvaRing'
has a different risk of venous thromboembolism than
second generation oral contraceptives. A
two- to four-fold increase in relative risk of
post-operative thromboembolic complications has been
reported with the use of oral contraceptives. The
relative risk of venous thrombosis in women who have
predisposing conditions is twice that of women without
such medical conditions. If feasible, combination
hormonal contraceptives, including NuvaRing', should be
discontinued at least four weeks prior to and for two
weeks after elective surgery of a type associated with
an increase in risk of thromboembolism and during and
following prolonged immobilization. Since the immediate
postpartum period is also associated with an increased
risk of thromboembolism, combination hormonal
contraceptives, such as NuvaRing', should be started no
earlier than four to six weeks after delivery in women
who elect not to breast-feed. The
clinician should be alert to the earliest manifestations
of thrombotic disorders (thrombophlebitis, pulmonary
embolism, cerebrovascular disorders, and retinal
thrombosis). Should any of these occur or be suspected,
NuvaRing' should be discontinued
immediately.<br/>b.
Myocardial Infarction: An
increased risk of myocardial infarction has been
attributed to oral contraceptive use. This risk is
primarily in smokers or women with other underlying risk factors for coronary artery disease such as
hypertension, hypercholesterolemia, morbid obesity, and
diabetes. The relative risk of heart attack for current
combination oral contraceptive users has been estimated
to be two to six. The risk is very low in women under
the age of 30. Smoking in combination with oral contraceptive use has
been shown to contribute substantially to the incidence
of myocardial infarction in women in their mid-thirties
or older with smoking accounting for the majority of
excess cases. Mortality rates associated with
circulatory disease have been shown to increase
substantially in smokers, over the age of 35 and
non-smokers over the age of 40 among women who use oral
contraceptives (see Table IV). Oral contraceptives may compound the effects of
well-known risk factors, such as hypertension, diabetes,
hyperlipidemias, age, and obesity. In particular, some
progestogens are known to decrease HDL cholesterol and
cause glucose intolerance, while estrogens may create a
state of hyperinsulinism. Oral contraceptives have been
shown to increase blood pressure among users (see
WARNINGS). Similar effects on risk
factors have been associated with an increased risk of
heart disease. NuvaRing' must be used with caution in
women with cardiovascular disease risk
factors.<br/>c.
Cerebrovascular Diseases: Oral contraceptives have been shown to increase both
the relative and attributable risks of cerebrovascular
events (thrombotic and hemorrhagic strokes), although,
in general, the risk is greatest among older (>35
years), hypertensive women who also smoke. Hypertension
was found to be a risk factor for both users and
non-users, for both types of strokes, while smoking
interacted to increase the risk for hemorrhagic strokes. In
a large study, the relative risk of thrombotic strokes
has been shown to range from three for normotensive
users to 14 for users with severe hypertension. The
relative risk of hemorrhagic stroke is reported to be
1.2 for non-smokers who used oral contraceptives, 2.6
for smokers who did not use oral contraceptives, 7.6 for
smokers who used oral contraceptives, 1.8 for
normotensive users and 25.7 for users with severe
hypertension. The attributable risk is also greater in
older women. Oral contraceptives also increase the risk
for stroke in women with other underlying risk factors
such as certain inherited or acquired thrombophilias,
hyperlipidemias, and obesity. Women with migraine
(particularly migraine with aura) who take combination
oral contraceptives may be at an increasedrisk of
stroke.<br/>d.
Dose-related risk of vascular disease from oral
contraceptives: A
positive association has been observed between the
amount of estrogen and progestogen in oral
contraceptives and the risk of vascular disease. A
decline in serum high-density lipoproteins (HDL) has
been reported with many progestational agents. A decline
in serum high-density lipoproteins has been associated
with an increased incidence of ischemic heart disease.
Because estrogens increase HDL cholesterol, the net
effect of an oral contraceptive depends on a balance
achieved between doses of estrogen and progestogen and
the nature and absolute amount of progestogensused in
the contraceptives. The activity and amount of both
hormones should be considered in the choice of a
hormonal contraceptive. Minimizing exposure to estrogen and progestogen is in
keeping with good principles of therapeutics. For any
particular estrogen/progestogen combination, the dosage
regimen prescribed should be one which contains the
least amount of estrogen and progestogen that is
compatible with a low failure rate and the needs of the
individual patient. New acceptors of hormonal
contraceptive agents should be started on a product
containing the lowest hormone content that provides
satisfactory results in the individual.<br/>e.
Persistence of risk of vascular disease: There are two studies that have shown persistence of
risk of vascular disease for ever-users of oral
contraceptives. In a study in the United States, the
risk of developing myocardial infarction after
discontinuing oral contraceptives persists for at least
nine years for women 40-49 years old who had used oral
contraceptives for five or more years, but this
increased risk was not demonstrated in other age groups.
In another study in Great Britain, the risk of
developing cerebrovascular disease persisted for at
least six years after discontinuation of oral
contraceptives, although excess risk was very small.
However, both studies were performed with oral
contraceptive formulations containing 50 micrograms or
more of estrogen. It
is unknown whether NuvaRing' is distinct from
combination oral contraceptives with regard to the
occurrence of venous or arterial thrombosis.<br/>2. ESTIMATES OF
MORTALITY FROM CONTRACEPTIVE USE: One study
gathered data from a variety of sources that have estimated the
mortality rate associated with different methods of
contraception at different ages (Table V). These estimates
include the combined risk of death associated with contraceptive
methods plus the risk attributable to pregnancy in the event of
method failure. Each method of contraception has its specific
benefits and risks. The study concluded that with the exception
of oral contraceptive users age 35 and older who smoke and age
40 and older who do not smoke, mortality associated with all
methods of birth control is low and below that associated with
childbirth. The
observation of a possible increase in risk of mortality with age
for oral contraceptive users is based on data gathered in the
1970's, but not reported until 1983. However, current clinical
practice involves the use of lower estrogen-dose formulations
combined with careful restriction of hormonal contraceptive use
to women who do not have the various risk factors listed in this
labeling. Because of
these changes in practice and, also, because of some limited new
data which suggest that the risk of cardiovascular disease with
the use of oral contraceptives may now be less than previously
observed, the Fertility and Maternal Health Drugs Advisory
Committee was asked to review the topic in 1989. The Committee
concluded that although cardiovascular disease risks may be
increased with oral contraceptive use after age 40 in healthy
non-smoking women (even with the newer low-dose formulations),
there are also greater potential health risks associated with
pregnancy in older women and with the alternative surgical and
medical procedures which may be necessary if such women do not
have access to effective and acceptable means of contraception.
Therefore, the Committee recommended that the benefits of
low-dose hormonal oral contraceptive use by healthy non-smoking
women over 40 may outweigh the possible risks. Older women, as
all women who take hormonal contraceptives, should take the
lowest possible dose formulation that is effective and meets the
individual patient needs.<br/>3. CARCINOMA OF THE
REPRODUCTIVE ORGANONS AND BREASTS: Numerous
epidemiologic studies have been performed on the incidence of
breast, endometrial, ovarian, and cervical cancer in women using
combination oral contraceptives. Although the risk of breast
cancer may be slightly increased among current users of oral
contraceptives (RR = 1.24), this excess risk decreases over time
after oral contraceptive discontinuation and by 10 years after
cessation the increased risk disappears. The risk does not
increase with duration of use, and no relationships have been
found with dose or type of steroid. The patterns of risk are
also similar regardless of a woman's reproductive history or her
family breast cancer history. The subgroup for whom risk has
been found to be significantly elevated is women who first used
oral contraceptives before age 20, but because breast cancer is
so rare at these young ages, the number of cases attributable to
this early oral contraceptive use is extremely small. Breast
cancers diagnosed in current or previous oral contraceptive
users tend to be less advanced clinically than in never-users.
Women who currently have or have had breast cancer should not
use hormonal contraceptives because breast cancer is a
hormone-sensitive tumor. Some
studies suggest that combination oral contraceptive use has been
associated with an increase in the risk of cervical
intraepithelial neoplasia in some populations of women. However,
there continues to be controversy about the extent to which such
findings may be due to differences in sexual behavior and other
factors. In spite of
many studies of the relationship between oral contraceptive use
and breast and cervical cancers, a cause-and-effect relationship
has not been established. It is
unknown whether NuvaRing' is distinct from oral contraceptives
with regard to the above statements.<br/>4. HEPATIC
NEOPLASIA: Benign
hepatic adenomas are associated with oral contraceptive use,
although the incidence of benign tumors is rare in the United
States. Indirect calculations have estimated the attributable
risk to be in the range of 3.3 cases per 100,000 for users, a
risk that increases after four or more years of use. Rupture of
rare, benign, hepatic adenomas may cause death through
intra-abdominal hemorrhage. Studies
from Britain have shown an increased risk of developing
hepatocellular carcinoma in long term (>8 years) oral
contraceptive users. However, these cancers are extremely rare
in the US and the attributable risk (the excess incidence) of
liver cancers in oral contraceptive users approaches less than
one per million users. It is unknown whether NuvaRing' is
distinct from oral contraceptives in this regard.<br/>5. OCULAR LESIONS: There have
been clinical case reports of retinal thrombosis associated with
the use of oral contraceptives. NuvaRing' should be discontinued
if there is unexplained partial or complete loss of vision,
onset of proptosis or diplopia, papilledema, or retinal vascular
lesions. Appropriate diagnostic and therapeutic measures should
be undertaken immediately.<br/>6. HORMONAL
CONTRACEPTIVE USE BEFORE OR DURING EARLY PREGNANCY: Hormonal
contraceptives should not be used during pregnancy. Extensive
epidemiologic studies have revealed no increased risk of birth
defects in women who have used oral contraceptives prior to
pregnancy. Studies also do not suggest a teratogenic effect,
particularly in so far as cardiac anomalies and limb reduction
defects are concerned, when oral contraceptives are taken
inadvertently during early pregnancy. Combination
hormonal contraceptives, such as NuvaRing', should not be used
to induce withdrawal bleeding as a test for pregnancy. NuvaRing'
should not be used during pregnancy to treat threatened or
habitual abortion. It is recommended that for any woman who has
not adhered to the prescribed regimen for use of NuvaRing' and
has missed a menstrual period or who has missed two consecutive
periods, pregnancy should be ruled out.<br/>7. GALLBLADDER
DISEASE: Combination
hormonal contraceptives, such as NuvaRing', may worsen existing
gallbladder disease and may accelerate the development of this
disease in previously asymptomatic women. Women with a history
of combination hormonal contraceptive-related cholestasis are
more likely to have the condition recur with subsequent
combination hormonal contraceptive use.<br/>8. CARBOHYDRATE AND
LIPID METABOLIC EFFECTS: Hormonal
contraceptives have been shown to cause a decrease in glucose
tolerance in some users. However, in the non-diabetic woman,
combination hormonal contraceptives appear to have no effect on
fasting blood glucose. Prediabetic and diabetic women should be
carefully observed while taking combination hormonal
contraceptives, such as NuvaRing'. In a clinical study involving
37 NuvaRing'-treated subjects, glucose tolerance tests showed no
clinically significant changes in serum glucose levels from
baseline to cycle six. A small
proportion of women will have persistent hypertriglyceridemia
while using oral contraceptives. Changes in serum triglycerides
and lipoprotein levels have been reported in combination
hormonal contraceptive users.<br/>9. ELEVATED BLOOD
PRESSURE: Women with
severe hypertension should not be started on hormonal
contraceptives. An increase in blood pressure has been reported
in women taking oral contraceptives and this increase is more
likely in older oral contraceptive users and with continued use.
Data from the Royal College of General Practitioners and
subsequent randomized trials have shown that the incidence of
hypertension increases with increasing concentrations of
progestogens. Women with
a history of hypertension or hypertension-related diseases, or
renal disease should be encouraged to use another method of
contraception. If these women elect to use NuvaRing', they
should be monitored closely and if significant elevation of
blood pressure occurs, NuvaRing' should be discontinued. For
most women, elevated blood pressure will return to normal after
stopping hormonal contraceptives, and there is no difference in
the occurrence of hypertension between former and
never-users.<br/>10. HEADACHE: The onset
or exacerbation of migraine or development of headache with a
new pattern which is recurrent, persistent, or severe requires
discontinuation of NuvaRing' and evaluation of the
cause.<br/>11. BLEEDING
IRREGULARITIES:<br/>Bleeding Patterns: Breakthrough bleeding and spotting are sometimes
encountered in women using NuvaRing'. If abnormal
bleeding while using NuvaRing' persists or is severe,
appropriate investigation should be instituted to rule
out the possibility of organic pathology or pregnancy,
and appropriate treatment should be instituted when
necessary. In the event of amenorrhea, pregnancy should
be ruled out. Bleeding patterns were evaluated in three large
clinical studies. In the US-Canadian study (n=1177), the
percentages of subjects with breakthrough
bleeding/spotting ranged from 7.2 to 11.7% during cycles
1-13. In the two non-US studies, the percentages of
subjects with breakthrough bleeding/spotting ranged from
2.6 to 6.4% (Study 1, n=1145 European and Israeli
subjects) and from 2.0 to 8.7% (Study 2, n=512 European
and South American subjects). In these three studies,
the percentages of women who did not have withdrawal
bleeding in a given cycle ranged from 0.3 to 3.8%. Some women may encounter amenorrhea or oligomenorrhea
after discontinuing use of NuvaRing', especially when
such a condition was pre-existent.<br/>12. ECTOPIC
PREGNANCY: Ectopic as
well as intrauterine pregnancy may occur in contraceptive
failures.
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| dailymed-drugs:25 |
Clinical Worsening and Suicide Risk: Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (aged 18-24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there wasa reduction with antidepressants compared to placebo in adults aged 65 and older. The pooled analysis of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders including a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs placebo), however, were relatively stable with age strada and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table 1. No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide. It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression. All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and non-psychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers. Such monitoring should include daily observation by families and caregivers. Prescriptions for Surmontil should be written for the smallest quantity of capsules consistent with good patient management, in order to reduce the risk of overdose. Screening Patients for Bipolar Disorder: A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment withan antidepressant, patients with depression symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that Surmontil is not approved for use in treating bipolar depression.<br/>General Consideration for Use: Extreme caution should be used when this drug is given to patients with any evidence of cardiovascular disease because of the possibility of conduction defects, arrhythmias, myocardial infarction, strokes, and tachycardia. Caution is advised in patients with increased intraocular pressure, history of urinary retention, or history of narrow-angle glaucoma because of the drug's anticholinergic properties; hyperthyroid patients or those on thyroid medication because of the possibility of cardiovascular toxicity; patients with a history of seizure disorder, because this drug has been shown to lower the seizure threshold; patients receiving guanethidine or similar agents, since Surmontil (trimipramine maleate) may block the pharmacologic effects of these drugs. Since the drug may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as operating an automobile or machinery, the patient should be cautioned accordingly.
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| dailymed-drugs:26 |
Instructions for inserting and removing LACRISERT should be carefully followed.
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| dailymed-drugs:27 |
Clinical Worsening and Suicide Risk: Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18 to 24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reductionwith antidepressants compared to placebo in adults aged 65 and older. The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs. placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the numberof cases of suicidality per 1000 patients treated) are provided in Table 1. No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide. It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression. All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms . Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers. Such monitoring should include daily observation by families and caregivers. Prescriptions for sertraline hydrochloride should be written for the smallest quantity consistent with good patient management, in order to reduce the risk of overdose. A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that sertraline hydrochloride is not approved for use in treating bipolar depression. Cases of serious sometimes fatal reactions have been reported in patients receiving sertraline hydrochloride, a selective serotonin reuptake inhibitor (SSRI), in combination with a monoamine oxidase inhibitor (MAOI). Symptoms of a drug interaction between an SSRI and an MAOI include: hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, mental status changes that include confusion, irritability, and extreme agitation progressing to delirium and coma. These reactions have also been reported in patients who have recently discontinued an SSRI and have been started on an MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. Therefore, sertraline hydrochloride should not be used in combination with an MAOI, or within 14 days of discontinuing treatment with an MAOI. Similarly, at least 14 days should be allowed after stopping sertraline hydrochloride before starting an MAOI. The concomitant use of sertraline hydrochloride with MAOIs intended to treat depression is contraindicated<br/>Serotonin Syndrome: The development of a potentially life-threatening serotonin syndrome may occur in treatment with SNRIs and SSRIs, including sertraline hydrochloride, particularly with concomitant use of serotonergic drugs (including triptans) and with drugs which impair metabolism of serotonin (including MAOIs). Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). If concomitant treatment of SNRIs and SSRIs, including sertraline hydrochloride, with a 5-hydroxytryptamine receptor agonist (triptan) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases . The concomitant use of SNRIs and SSRIs, including sertraline hydrochloride, with serotonin precursors (such as tryptophan) is not recommended .
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| dailymed-drugs:28 |
14.6% Sodium Chloride Injection, USP is hypertonic and must
be diluted prior to administration. Inadvertent direct injection or absorption
of concentrated sodium chloride solution may give rise to sudden hypernatremia
and such complications as cardiovascular shock, central nervous system disorders,
extensive hemolysis, cortical necrosis of the kidneys and severe local tissue
necrosis (if administered extravascularly). Solutions
containing sodium ions should be used with great care, if at all, in patients
with congestive heart failure, severe renal insufficiency and in clinical
states in which there exists edema with sodium retention. In
patients with diminished renal function, administration of solutions containing
sodium may result in sodium retention. The intravenous
administration of this solution (after appropriate dilution) can cause fluid
and/or solute overload resulting in dilution of other serum electrolyte concentrations,
overhydration, congested states or pulmonary edema. Excessive
administration of potassium free solutions may result in significant hypokalemia. WARNING:
This product contains aluminum that may be toxic. Aluminum may reach toxic
levels with prolonged parenteral administration if kidney function is impaired.
Premature neonates are particularly at risk because their kidneys are immature,
and they require large amounts of calcium and phosphate solutions, which contain
aluminum. Research indicates that patients with impaired
kidney function, including premature neonates, who receive parenteral levels
of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels
associated with central nervous system and bone toxicity. Tissue loading may
occur at even lower rates of administration.
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| dailymed-drugs:29 |
Propoxyphene products in excessive doses, either alone or in combination with other CNS depressants, including alcohol, are a major cause of drug-related deaths. Fatalities within the first hour of overdosage are not uncommon. In a survey of deaths due to overdosage conducted in 1975, in approximately 20% of the fatal cases, death occurred within the first hour (5% occurred within 15 minutes). Propoxyphene should not be taken in doses higher than those recommended by the physician. The judicious prescribing of propoxyphene is essential to the safe use of this drug. With patients who are depressed or suicidal, consideration should be given to the use of non-narcotic analgesics. Patients should be cautioned about the concomitant useof propoxyphene products and alcohol because of potentially serious CNS-additive effects of these agents. Because of its added depressant effects, propoxyphene should be prescribed with caution for those patients whose medical condition requires the concomitant administration of sedatives, tranquilizers, muscle relaxants, antidepressants, or other CNS-depressant drugs. Patients should be advised of the additive depressant effects of these combinations. Many of the propoxyphene-related deaths have occurred in patients with previous histories of emotional disturbances or suicidal ideation or attempts as well as histories of misuse of tranquilizers, alcohol, and other CNS-active drugs. Some deaths have occurred as a consequence of the accidental ingestion of excessive quantities of propoxyphene alone or in combination with other drugs. Patients taking propoxyphene should be warned not to exceed the dosage recommended by the physician.
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| dailymed-drugs:35 |
CARDIOVASCULAR EFFECTS:<br/>Cardiovascular Thrombotic Events: Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the signs and/or symptoms of serious CV events and the steps to take if they occur. There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID does increase the risk of serious GI events (see WARNINGS, Gastrointestinal Effects���Risk of Ulceration, Bleeding, and Perforation). Two large, controlled, clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke (see CONTRAINDICATIONS).<br/>Hypertension: NSAIDs, including etodolac, can lead to onset of new hypertension or worsening of pre- existing hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including etodolac, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.<br/>Congestive Heart Failure and Edema: Fluid retention and edema have been observed in some patients taking NSAIDs. Etodolac should be used with caution in patients with fluid retention or heart failure.<br/>Gastrointestinal Effects- Risk of Ulceration, Bleeding, and Perforation: NSAIDs, including etodolac, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients, who develop a serious upper GI adverse event on NSAID therapy, is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3-6 months, and in about 2-4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a seriousGI event at some time during the course of therapy. However, even short-term therapy is not without risk. Physicians should inform patients about the signs and/or symptoms of serious GI toxicity and what steps to take if they occur. NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease, and/or gastrointestinal bleeding, and who use NSAIDs have a greater than 10-fold increased risk for developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients, and therefore, special care should be taken in treating this population. To minimize the potential risk for an adverse GI event in patients treated with an NSAID, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high risk patients, alternate therapies that do not involve NSAIDs should be considered.<br/>Renal Effects: Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a nonsteroidal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greater risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state. Renal pelvic transitional epithelial hyperplasia, a spontaneous change occurring with variable frequency, was observed with increased frequency in treated male rats in a 2-year chronic study.<br/>Advanced Renal Disease: No information is available from controlled clinical studies regarding the use of etodolac in patients with advanced renal disease. Therefore, treatment with etodolac is not recommended in these patients with advanced renal disease. If etodolac therapy must be initiated, close monitoring of the patient's renal function is advisable.<br/>Anaphylactoid Reactions: As with other NSAIDS, anaphylactoid reactions may occur in patients without prior exposure to etodolac. Etodolac should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs. Fatal reactions have been reported in such patients (see CONTRAINDICATIONS and PRECAUTIONS, General, Pre-existing Asthma). Emergency help should be sought in cases wherean anaphylactoid reaction occurs.<br/>Skin Reactions: NSAIDs, including etodolac, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Patients should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.<br/>Pregnancy: In late pregnancy, the third trimester, as with other NSAIDs, etodolac should be avoided because it may cause premature closure of the ductus arteriosus (see PRECAUTIONS, Pregnancy, Nonteratogenic Effects).
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| dailymed-drugs:36 |
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on oral penicillin therapy. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral penicillins. These reactions are more apt to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe hypersensitivity reactions when treated with a cephalosporin, and vice versa. Before initiating therapy with a penicillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, the drug should be discontinued and the appropriate therapy instituted. SERIOUS ANAPHYLACTOID REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE. OXYGEN, INTRAVENOUS STEROIDS AND AIRWAY MANAGEMENT, INCLUDING INTUBATION, SHOULD ALSO BE ADMINISTERED AS INDICATED. Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including GEOCILLIN(carbenicillin indanyl sodium ), and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
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| dailymed-drugs:37 |
Agranulocytosis: In premarketing clinical trials, two (one with Sj��gren's Syndrome) out of 2,796 patients treated with mirtazapine developed agranulocytosis (absolute neutrophil count (ANC)<500/mmwith associated signs and symptoms, e.g., fever, infection, etc.) and a third patient developed severe neutropenia (ANC<500/mmwithout any associated symptoms). For these three patients, onset of severe neutropenia was detected on days 61, 9, and 14 of treatment, respectively. All three patients recovered after mirtazapine was stopped. These three cases yield a crude incidence of severe neutropenia (with or without associated infection) of approximately 1.1 per thousand patients exposed, with a very wide 95% confidence interval, i.e., 2.2 cases per 10,000 to 3.1 cases per 1000. If a patient develops a sore throat, fever, stomatitis or other signs of infection, along with a low WBC count, treatment with mirtazapine should be discontinued and the patient should be closely monitored.<br/>MAO Inhibitors: In patients receiving other drugs for major depressive disorder in combination with a monoamine oxidase inhibitor (MAOI) and in patients who have recently discontinued a drug for major depressive disorder and then are started on an MAOI, there have been reports of serious, and sometimes fatal, reactions, e.g., including nausea, vomiting, flushing, dizziness, tremor, myoclonus, rigidity, diaphoresis, hyperthermia, autonomic instability with rapid fluctuations of vital signs, seizures, and mental status changes ranging from agitation to coma. Although there are no human data pertinent to such an interaction with mirtazapine tablets, it is recommended that mirtazapine not be used in combination with an MAOI, or within 14 days of initiating or discontinuing therapy with an MAOI.<br/>Clinical Worsening and Suicide Risk: Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking anti-depressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a longstanding concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18-24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older. The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs placebo), however, were relatively stable within age strata and across indications. The risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table 1. No suicides occurred in any of the pediatric trials. There were suicides in adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide. It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that use of antidepressants can delay the recurrence of depression. All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dosage changes, either increases or decreases. The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Families and caregivers of pediatric patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers. Such monitoring should include daily observation by families and caregivers. Prescriptions for mirtazapine should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose. Screening Patients for Bipolar Disorder: A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that Mirtazapine is not approved for use in treating bipolar depression.
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| dailymed-drugs:38 |
Irinotecan Hydrochloride Injection should be administered only under the supervision of a physician who is experienced in the use of cancer chemotherapeutic agents. Appropriate management of complications is possible only when adequate diagnostic and treatment facilities are readily available. Irinotecan Hydrochloride Injection can induce both early and late forms of diarrhea that appear to be mediated by different mechanisms. Both formsof diarrhea may be severe. Early diarrhea (occurring during or shortly after infusion of Irinotecan Hydrochloride Injection) may be accompanied by cholinergic symptoms of rhinitis, increased salivation, miosis,lacrimation, diaphoresis, flushing, and intestinal hyperperistalsis that can cause abdominal cramping. Early diarrhea and other cholinergic symptoms may be prevented or ameliorated by atropine . Late diarrhea (generally occurring more than 24 hours after administration of Irinotecan Hydrochloride Injection) can be life threatening since it may be prolonged and may lead to dehydration, electrolyte imbalance, or sepsis. Late diarrhea should be treated promptly with loperamide. Patients with diarrhea should be carefully monitored and given fluid and electrolyte replacement if they become dehydrated or antibiotic therapy if they develop ileus, fever, or severe neutropenia . Administration of Irinotecan Hydrochloride Injection should be interrupted and subsequent doses reduced if severe diarrhea occurs . Severe myelosuppression may occur .
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| dailymed-drugs:39 |
Progestins and estrogens should not be used for the prevention of cardiovascular disease. The Women's Health Initiative (WHI) study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50 to 79 years of age) during 5 years of treatment with oral conjugated estrogens (CE 0.625 mg) combined with medroxyprogesterone acetate (MPA 2.5 mg) relative to placebo. The Women's Health Initiative Memory Study (WHIMS), a substudy of WHI, reported increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with oral conjugated estrogens plus medroxyprogesterone acetate relative to placebo. It is unknown whether this finding applies to younger postmenopausal women. Other doses of oral conjugated estrogens with medroxyprogesterone and other combinations and dosage forms of estrogens and progestins were not studied in the WHI clinical trials. In the absence of comparable data and product-specific studies, the relevance of the WHI findings to other products has not been established. Therefore, the risks should be assumed to be similar for all estrogen and progestin products. Because of these risks, estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.
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| dailymed-drugs:41 |
Intravenous infusion of amino acids may induce a
rise in blood urea nitrogen (BUN), especially in patients with impaired
hepatic or renal function. Appropriate laboratory tests should be
performed periodically and infusion discontinued if BUN levels exceed
normal postprandial limits and continue to rise. It should be noted
that a modest rise in BUN normally occurs as a result of increased
protein intake. Administration of amino acid
solutions to a patient with hepatic insufficiency may result in serum
amino acid imbalances, metabolic alkalosis, prerenal azotemia, hyperammonemia,
stupor and coma. Administration of amino acid
solutions in the presence of impaired renal function may augment an
increasing BUN, as does any protein dietary component. Solutions containing sodium ion should be used with great
care, if at all, in patients with congestive heart failure, severe
renal insufficiency and in clinical states in which there exists edema
with sodium retention. Solutions which contain
potassium ion should be used with great care, if at all, in patients
with hyperkalemia, severe renal failure and in conditions in which
potassium retention is present. Solutions containing
acetate ion should be used with great care in patients with metabolic
or respiratory alkalosis. Acetate should be administered with great
care in those conditions in which there is an increased level or an
impaired utilization of this ion, such as severe hepatic insufficiency. Hyperammonemia is of special significance in infants,
as it can result in mental retardation. Therefore, it is essential
that blood ammonia levels be measured frequently in infants. Instances of asymptomatic hyperammonemia have been reported
in patients without overt liver dysfunction. The mechanisms of this
reaction are not clearly defined, but may involve genetic defects
and immature or subclinically impaired liver function. Aminosyn, Sulfite-Free, (a crystalline amino acid solution)
can be infused simultaneously with fat emulsion by means of a Y-connector
located near the infusion site using separate flow rate controls for
each solution. WARNING: This product contains
aluminum that may be toxic. Aluminum may reach toxic levels with prolonged
parenteral administration if kidney function is impaired. Premature
neonates are particularly at risk because their kidneys are immature,
and they require large amounts of calcium and phosphate solutions,
which contain aluminum. Research indicates that
patients with impaired kidney function, including premature neonates,
who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day
accumulate aluminum at levels associated with central nervous system
and bone toxicity. Tissue loading may occur at even lower rates of
administration.
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| dailymed-drugs:42 |
Because rare
instances of anaphylactoid reactions have occurred in patients receiving
parenteral corticosteroid therapy, appropriate precautionary measures
should be taken prior to administration, especially when the patient has
a history of allergy to any drug. Anaphylactoid and hypersensitivity
reactions have been reported for Dexamethasone Sodium Phosphate
Injection (see ADVERSE
REACTIONS). Dexamethasone
Sodium Phosphate Injection contains sodium sulfite, a sulfite that may
cause allergic-type reactions including anaphylactic symptoms and
life-threatening or less severe asthmatic episodes in certain
susceptible people. The overall prevalence of sulfite sensitivity in the
general population is unknown and probably low. Sulfite sensitivity is
seen more frequently in asthmatic than in nonasthmatic people. Corticosteroids may
exacerbate systemic fungal infections and, therefore, should not be used
in the presence of such infections unless they are needed to control
drug reactions due to amphotericin B. Moreover, there have been cases
reported in which concomitant use of amphotericin B and hydrocortisone
was followedby cardiac enlargement and congestive failure. In patients on
corticosteroid therapy subjected to unusual stress, increased dosage of
rapidly acting corticosteroids before, during and after the stressful
situation is indicated. Drug-induced
secondary adrenocortical insufficiency may result from too rapid
withdrawal of corticosteroids and may be minimized by gradual reduction
of dosage. This type of relative insufficiency may persist for months
after discontinuation of therapy; therefore, in any situation of stress
occurring during that period, hormone therapy should be reinstituted. If
the patient is receiving steroids already, dosage may have to be
increased. Since mineralocorticoid secretion may be impaired, salt
and/or a mineralocorticoid should be administered concurrently. Corticosteroids may
mask some signs of infection, and new infections may appear during their
use. There may be decreased resistance and inability to localize
infections when corticosteroids are used. Moreover, corticosteroids may
affect the nitroblue-tetrazolium test for bacterial infection and
produce false-negative results. In cerebral
malaria, a double blind trial has shown that the use of corticosteroids
is associated with prolongation of coma and a higher incidence of
pneumonia and gastrointestinal bleeding. Corticosteroids may
activate latent amebiasis. Therefore, it is recommended that latent or
active amebiasis be ruled out before initiating corticosteroid therapy
in any patient who has spent time in the tropics or in any patient with
unexplained diarrhea. Prolonged use of
corticosteroids may produce posterior subcapsular cataracts, glaucoma
with possible damage to the optic nerves and may enhance the
establishment of secondary ocular infections due to fungi or viruses. Average and large
doses of cortisone or hydrocortisone can cause elevation of blood
pressure, salt and water retention and increased excretion of potassium.
These effects are less likely to occur with the synthetic derivatives
except when used in large doses. Dietary salt restriction and potassium
supplementation may be necessary. All corticosteroids increase calcium
excretion. Administration of
live virus vaccines, including smallpox, is contraindicated in
individuals receiving immunosuppressive doses of corticosteroids. If
inactivated viral or bacterial vaccines are administered to individuals
receiving immunosuppressive doses of corticosteroids, the expected serum
antibody response may not be obtained. However, immunization procedures
may be undertaken in patients who are receiving corticosteroids as
replacement therapy, e.g., for Addison's disease. Persons who are on
drugs which suppress the immune system are more susceptible to
infections than healthy individuals. Chickenpox and measles, for
example, can have a more serious or even fatal course in non-immune
children or adults on corticosteroids. In such children or adults who
have not had these diseases, particularcare should be taken to avoid
exposure. How the dose, route and duration of corticosteroid
administration affects the risk of developing a disseminated infection
is unknown. The contribution of the underlying disease and/or prior
corticosteroid treatment to the risk is also not known. If exposed to
chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may
be indicated. If exposed to measles, prophylaxis with pool intramuscular
immune globulin (IG) may be indicated. (See the respective package
inserts for VZIG and IG for complete prescribing information.) If
chickenpox develops, treatment with antiviral agents may be considered. The use of Dexamethasone Sodium Phosphate Injection in active tuberculosis should
be restricted to those cases of fulminating or disseminated tuberculosis in which the corticosteroid is used for the management of the disease in
conjunction with an appropriate antituberculosis regimen. If corticosteroids
are indicated in patients with latent tuberculosis or tuberculin
reactivity, close observation is necessary as reactivation of the
disease may occur. During prolonged corticosteroid therapy, these
patients should receive chemoprophylaxis. Literature reports
suggest an apparent association between use of corticosteroids and left
ventricular free wall rupture after a recent myocardial infarction;
therefore, therapy with corticosteroids should be used with great
caution in these patients.<br/>Usage in Pregnancy: Since
adequate human reproduction studies have not been done with
corticosteroids, use of these drugs in pregnancy or in women of
childbearing potential requires that the anticipated benefits be
weighed against the possible hazards to the mother and embryo or
fetus. Infants born of mothers who have received substantial
doses of corticosteroids during pregnancy should be carefully
observed for signs of hypoadrenalism. Corticosteroids appear in breast milk and could suppress
growth, interfere with endogenous corticosteroid production or
cause other unwanted effects. Mothers taking pharmacologic doses
of corticosteroids should be advised not to nurse.
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| dailymed-drugs:43 |
THE 0.75% CONCENTRATION
OF BUPIVACAINE HYDROCHLORIDE IS NOT RECOMMENDED FOR OBSTETRICAL ANESTHESIA. THERE HAVE BEEN
REPORTS OF CARDIAC ARREST WITH DIFFICULT RESUSCITATION OR DEATH DURING
USE OF BUPIVACAINE HYDROCHLORIDE FOR EPIDURAL ANESTHESIA IN OBSTETRICAL
PATIENTS. IN MOST CASES, THIS HAS FOLLOWED USE OF THE 0.75% CONCENTRATION.
RESUSCITATION HAS BEEN DIFFICULT OR IMPOSSIBLE DESPITE APPARENTLY
ADEQUATE PREPARATION AND APPROPRIATE MANAGEMENT. CARDIAC ARREST HAS
OCCURRED AFTER CONVULSIONS RESULTING FROM SYSTEMIC TOXICITY, PRESUMABLY
FOLLOWING UNINTENTIONAL INTRAVASCULAR INJECTION. THE 0.75% CONCENTRATION
SHOULD BE RESERVED FOR SURGICAL PROCEDURES WHERE A HIGH DEGREE OF
MUSCLE RELAXATION AND PROLONGED EFFECT ARE NECESSARY. LOCAL ANESTHETICS SHOULD ONLY BE EMPLOYED BY CLINICIANS
WHO ARE WELL VERSED IN DIAGNOSIS AND MANAGEMENT OF DOSE-RELATED TOXICITY
AND OTHER ACUTE EMERGENCIES WHICH MIGHT ARISE FROM THE BLOCK TO BE
EMPLOYED, AND THEN ONLY AFTER INSURING THE IMMEDIATE AVAILABILITY OF OXYGEN, OTHER RESUSCITATIVE DRUGS,
CARDIOPULMONARY RESUSCITATIVE EQUIPMENT, AND THE PERSONNEL RESOURCES
NEEDED FOR PROPER MANAGEMENT OF TOXIC REACTIONS AND RELATED EMERGENCIES.
(See also ADVERSE REACTIONS, PRECAUTIONS, and OVERDOSAGE.) DELAY IN
PROPER MANAGEMENT OF DOSE-RELATED TOXICITY, UNDERVENTILATION FROM
ANY CAUSE, AND/OR ALTERED SENSITIVITY MAY LEAD TO THE DEVELOPMENT
OF ACIDOSIS, CARDIAC ARREST AND, POSSIBLY, DEATH. Local anesthetic solutions containing antimicrobial preservatives,
i.e., those supplied in multiple-dose vials, should not be used for
epidural or caudal anesthesia because safety has not been established
with regard to intrathecal injection, either intentionally or unintentionally,
of such preservatives. It is essential that
aspiration for blood or cerebrospinal fluid (where applicable) be
done prior to injecting any local anesthetic, both the original dose
and all subsequent doses, to avoid intravascular or subarachnoid injection.
However, a negative aspiration does not ensure against an intravascular
or subarachnoid injection. Bupivacaine Hydrochloride
with epinephrine 1:200,000 or other vasopressors should not be used
concomitantly with ergot-type oxytocic drugs, because a severe persistent
hypertension may occur. Likewise, solutions of Bupivacaine Hydrochloride
containing a vasoconstrictor, such as epinephrine, should be used
with extreme caution in patients receiving monoamineoxidase inhibitors
(MAOI) or antidepressants of the triptyline or imipramine types, because
severe prolonged hypertension may result. Until
further experience is gained in pediatric patients younger than 12
years, administration of Bupivacaine Hydrochloride in this age group
is not recommended. Mixing or the prior or intercurrent
use of any other local anesthetic with Bupivacaine Hydrochloride cannot
be recommended because of insufficient data on the clinical use of
such mixtures. There have been reports of cardiac arrest and death
during the use of Bupivacaine Hydrochloride for intravenous regional
anesthesia (Bier Block). Information on safe dosages and techniques
of administration of Bupivacaine Hydrochloride in this procedure is
lacking. Therefore, Bupivacaine Hydrochloride is not recommended for
use in this technique. Bupivacaine Hydrochloride with epinephrine 1:200,000 contains
sodium metabisulfite, a sulfite that may cause allergic-type reactions
including anaphylactic symptoms and life-threatening or less severe
asthmatic episodes in certain susceptible people. The overall prevalence
of sulfite sensitivity in the general population is unknown and probably
low. Sulfite sensitivity is seen more frequently in asthmatic than
in nonasthmatic people. Single-dose ampuls and single-dose vials of Bupivacaine Hydrochloride without epinephrine do not contain sodium
metabisulfite.
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| dailymed-drugs:47 |
Pheochromocytoma. Administration of angiographic media to patients known or suspected to have pheochromocytoma can cause dangerous changes in blood pressure. A minimum dose should be injected. The blood pressure should be carefully monitored and measures for controlling major fluctuations should be available. During aortography by the translumbar technique, extreme care is advised to avoid inadvertent intrathecal injection since the injection of even small amounts (5 mL to 7 mL) of the contrast medium may cause convulsions, permanent sequelae, or fatality. Should the accident occur, the patient should be placed upright to confine the hyperbaric solution to a low level, anesthesia may be required to control convulsions, and if there is evidence of a large dose having been administered, a careful cerebrospinal fluid exchange-washout should be considered.
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| dailymed-drugs:49 |
These injections are for compounding only, not
for direct infusion. Dilute before use
to a concentration which will, when administered with an amino acid
(nitrogen) source, result in an appropriate calorie to gram of nitrogen
ratio and which has an osmolarity consistent with the route of
administration. Unless
appropriately diluted, the infusion of hypertonic dextrose injection
into a peripheral vein may result in vein irritation, vein damage, and
thrombosis. Strongly hypertonic nutrient solutions should only be
administered through an indwelling intravenous catheter with the tip
located in a large central vein such as the superior vena cava. In very low birth
weight infants, excessive or rapid administration of dextrose injection
may result in increased serum osmolality and possible intracerebral
hemorrhage. WARNING: This
product contains aluminum that may be toxic. Aluminum may reach toxic
levels with prolonged parenteral administration if kidney function is
impaired. Premature neonates are particularly at risk because their
kidneys are immature, and they require large amounts of calcium and
phosphate solutions, which contain aluminum. Research indicates
that patients with impaired kidney function, including premature
neonates, who receive parenteral levels of aluminum at greater than 4 to
5��g/kg/day accumulate aluminum at levels associated with central
nervous system and bone toxicity. Tissue loading may occur at even lower
rates of administration. Administration by central venous catheter
should be used only by those familiar with this technique and its
complications.
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| dailymed-drugs:51 |
Minoxidil tablets contain the powerful antihypertensive agent, minoxidil, which may produce serious adverse effects. It can cause pericardial effusion, occasionally progressing to tamponade, and angina pectoris may be exacerbated. Minoxidil should be reserved for hypertensive patients who do not respond adequately to maximum therapeutic doses of a diuretic and two other antihypertensive agents. In experimental animals, minoxidil caused several kinds of myocardial lesions as well as other adverse cardiac effects (see Cardiac Lesions in Animals). Minoxidil must be administered under close supervision, usually concomitantly with therapeutic doses of a beta-adrenergic blocking agent to prevent tachycardia and increased myocardial workload. It must also usually be given with a diuretic, frequently one acting in the ascending limb of the loop of Henle, to prevent serious fluid accumulation. Patients with malignant hypertension and those already receiving guanethidine (see Warnings) should be hospitalized when minoxidil is first administered so that they can be monitored to avoid too rapid, or large orthostatic, decreases in blood pressure.
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| dailymed-drugs:52 |
Intravenous administration should not exceed 50 mg per minute in adults. In neonates, the drug should be administered at a rate not exceeding 1-3 mg/kg/min. Severe cardiotoxic reactions and fatalities have been reported with atrial and ventricular conduction depression and ventricular
fibrillation. Severe complications are most commonly encountered in elderly or gravely ill patients. Phenytoin should be used with caution in patients with hypotension and severe myocardial insufficiency. Hypotension usually occurs when the drug is administered rapidly by the intravenous route. The intramuscular route is not recommended for the treatment of status epilepticus since blood levels of phenytoin in the
therapeutic range cannot be readily achieved with doses and methods of administration ordinarily employed. There have been a number of reports suggesting a relationship between phenytoin and the development of lymphadenopathy (local or
generalized) including benign lymph node hyperplasia, pseudolymphoma, lymphoma and Hodgkin's Disease. Although a cause and effect relationship has not been established, the occurrence of
lymphadenopathy indicates the need to differentiate such a condition from other types of lymph node pathology. Lymph node involvement may occur with or without symptoms and signs
resembling serum sickness, e.g., fever, rash and liver involvement. In all cases of lymphadenopathy, follow-up observation for an extended period is indicated and every effort should be made to
achieve seizure control using alternative antiepileptic drugs. Acute alcoholic intake may increase phenytoin serum levels while chronic alcoholic use may decrease serum levels.<br/>Usage In Pregnancy: A number of reports suggest an association between the use of antiepileptic drugs by women with epilepsy and a higher incidence
of birth defects in children born to these women. Data are more extensive with respect to phenytoin and phenobarbital, but these are also the most commonly prescribed antiepileptic
drugs; less systematic or anecdotal reports suggest a possible similar association with the use of all known antiepileptic drugs. The reports suggesting a higher incidence of birth defects in children of drug-treated epileptic women cannot be regarded as
adequate to prove a definite cause and effect relationship. There are intrinsic methodologic problems in obtaining adequate data on drug teratogenicity in humans; genetic factors or
the epileptic condition itself may be more important than drug therapy in leading to birth defects. The great majority of mothers on antiepileptic medication deliver normal infants. It is important to note that antiepileptic drugs should not be discontinued in patients in whom the drug is administered to
prevent major seizures, because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life. In individual cases where the severity and
frequency of the seizure disorder are such that the removal of medication does not pose a serious threat to the patient, discontinuation of the drug may be considered prior to and
during pregnancy, although it cannot be said with any confidence that even minor seizures do not pose some hazard to the developing embryo or fetus. The prescribing physician will
wish to weigh these considerations in treating or counseling epileptic women of childbearing potential. In addition to the reports of increased incidence of congenital malformation, such as cleft lip/palate and heart malformations
in children of women receiving phenytoin and other antiepileptic drugs, there have more recently been reports of a fetal hydantoin syndrome. This consists of prenatal growth
deficiency, microcephaly and mental deficiency in children born to mothers who have received phenytoin, barbiturates, alcohol or trimethadione. However, these features are all
interrelated and are frequently associated with intrauterine growth retardation from other causes. There have been isolated reports of malignancies, including neuroblastoma, in children whose mothers received phenytoin during
pregnancy. An increase in seizure frequency during pregnancy occurs in a high proportion of patients, because of altered phenytoin
absorption or metabolism. Periodic measurement of serum phenytoin levels is particularly valuable in the management of a pregnant epileptic patient as a guide to an appropriate
adjustment of dosage. However, postpartum restoration of the original dosage will probably be indicated. Neonatal coagulation defects have been reported within the first 24 hours in babies born to epileptic mothers receiving
phenobarbital and/or phenytoin. Vitamin K has been shown to prevent or correct this defect and has been recommended to be given to the mother before delivery and the neonate after
birth.
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| dailymed-drugs:53 |
Hepatitis:: Rare cases of death or hospitalization due to severe liver injury have been reported post-marketing in association with the use of CASODEX. Hepatotoxicity in these reports generally occurred within the first three to four months of treatment. Hepatitis or marked increases in liver enzymes leading to drug discontinuation occurred in approximately 1% of CASODEX patients in controlled clinical trials. Serum transaminase levels should be measured prior to starting treatment with CASODEX, at regular intervals for the first four months of treatment, and periodically thereafter. If clinical symptoms or signs suggestive of liver dysfunction occur (e.g., nausea, vomiting, abdominal pain, fatigue, anorexia,���flu-like���symptoms, dark urine, jaundice, or right upper quadrant tenderness), the serum transaminases, in particular the serum ALT, should be measured immediately. If at any time a patient has jaundice, or their ALT rises above two times the upper limit of normal, CASODEX should be immediately discontinued with close follow-up of liver function.
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| dailymed-drugs:55 |
BEFORE CEPHALEXIN THERAPY IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY REACTIONS TO CEPHALOSPORINS AND PENICILLIN. CEPHALOSPORIN C DERIVATIVES SHOULD BE GIVEN CAUTIOUSLY TO PENICILLIN-SENSITIVE PATIENTS. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE EPINEPHRINE AND OTHER EMERGENCY MEASURES. There is some clinical and laboratory evidence of partial cross-allergenicity of the penicillins and the cephalosporins. Patients have been reported to have had severe reactions (including anaphylaxis) to both drugs. Any patient who has demonstrated some form of allergy, particularly to drugs, should receive antibiotics cautiously. No exception should be made with regard to Cephalexin Capsules, USP. Pseudomembranous colitis has been reported with nearly all antibacterial agents, including cephalexin, and may range from mild to life threatening. Therefore, it is important to consider this diagnosis in patients with diarrhea subsequent to the administration of antibacterial agents. Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is one primary cause of antibiotic-associated colitis. After the diagnosis of pseudomembranous colitis has been established, appropriate therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, andtreatment with an antibacterial drug clinically effective against Clostridium difficile colitis. Usage in Pregnancy���Safety of this product for use during pregnancy has not been established.
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| dailymed-drugs:58 |
Metformin Hydrochloride:<br/>Lactic acidosis: Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with glipizide and metformin hydrochloride tablets; when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis may also occur in association with a number of pathophysiologic conditions, including diabetes mellitus, and whenever there is significant tissue hypoperfusion and hypoxemia. Lactic acidosis is characterized by elevated blood lactate levels (>5 mmol/L), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. When metformin is implicated as the cause of lactic acidosis, metformin plasma levels>5 mcg/mL are generally found. The reported incidence of lactic acidosis in patients receiving metformin hydrochloride is very low (approximately 0.03 cases/1000 patient-years, with approximately 0.015 fatal cases/1000 patient-years). Reported cases have occurred primarily in diabetic patients with significant renal insufficiency, including both intrinsic renal disease and renal hypoperfusion, often in the setting of multiple concomitant medical/surgical problems and multiple concomitant medications. Patients with congestive heart failure requiring pharmacologic management, in particular those with unstable or acute congestive heart failure who are at risk of hypoperfusion and hypoxemia, are at increased risk of lactic acidosis. The risk of lactic acidosis increases with the degree of renal dysfunction and the patient's age. The risk of lactic acidosis may, therefore, be significantly decreased by regular monitoring of renal function in patients taking metformin and by use of the minimum effective dose of metformin. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. Glipizide and metformin hydrochloride tablet treatment should not be initiated in patients���80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced, as these patients are more susceptible to developing lactic acidosis. In addition, glipizide and metformin hydrochloride tablets should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration, or sepsis. Because impaired hepatic function may significantly limit the ability to clear lactate, glipizide and metformin hydrochloride tablets should generally be avoided in patients with clinical or laboratory evidence of hepatic disease. Patients should be cautioned against excessive alcohol intake, either acute or chronic, when taking glipizide and metformin hydrochloride tablets, since alcohol potentiates the effects of metformin hydrochloride on lactate metabolism. In addition, glipizide and metformin hydrochloride tablets should be temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure (see also PRECAUTIONS). The onset of lactic acidosis often is subtle, and accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. There may be associated hypothermia, hypotension, and resistant bradyarrhythmias with more marked acidosis. The patient and the patient's physician must be aware of the possible importance of such symptoms and the patient should be instructed to notify the physician immediately if they occur (see also PRECAUTIONS). Glipizide and metformin hydrochloride tablets should be withdrawn until the situation is clarified. Serum electrolytes, ketones, blood glucose, and if indicated, blood pH, lactate levels,and even blood metformin levels may be useful. Once a patient is stabilized on any dose level of glipizide and metformin hydrochloride tablets, gastrointestinal symptoms, which are common during initiation of therapy with metformin, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease. Levels of fasting venous plasma lactate above the upper limit of normal but less than 5 mmol/L in patients taking glipizide and metformin hydrochloride tablets do not necessarily indicate impending lactic acidosis and may be explainable by other mechanisms, such as poorly controlled diabetes or obesity, vigorous physical activity, or technical problems in sample handling. (See also PRECAUTIONS.) Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia). Lactic acidosis is a medical emergency that must be treated in a hospital setting. In a patient with lactic acidosis who is taking glipizide and metformin hydrochloride tablets, the drug should be discontinued immediately and general supportive measures promptly instituted. Because metformin hydrochloride is dialyzable (with a clearance of up to 170 mL/min under good hemodynamic conditions), prompt hemodialysis is recommended to correct the acidosis and remove the accumulated metformin. Such management often results in prompt reversal of symptoms and recovery. (See also CONTRAINDICATIONS and PRECAUTIONS.)<br/>SPECIAL WARNING ON INCREASED RISK OF CARDIOVASCULAR MORTALITY: The administration of oral hypoglycemic drugs has been reported to be associated with increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. This warning is based on the study conducted by the University Group Diabetes Program (UGDP), a long-term prospective clinical trial designed to evaluate the effectiveness of glucose-lowering drugs in preventing or delaying vascular complications in patients with non-insulin-dependent diabetes. The study involved 823 patients who were randomly assigned to one of four treatment groups (Diabetes 19 (Suppl. 2):747-830, 1970). UGDP reported that patients treated for 5 to 8 years with diet plus a fixed dose of tolbutamide (1.5 grams per day) had a rate of cardiovascular mortality approximately 2��times that of patients treated with diet alone. A significant increase in total mortality was not observed, but the use of tolbutamide was discontinued based on the increase in cardiovascular mortality, thus limiting the opportunity for the study to show an increase in overall mortality. Despite controversy regarding the interpretation of these results, the findings of the UGDP study provide an adequate basis for this warning. The patient should be informed of the potential risks and benefits of glipizide and of alternative modes of therapy. Although only one drug in the sulfonylurea class (tolbutamide) was included in this study, it is prudent from a safety standpoint to consider that this warning may also apply to other hypoglycemic drugs in this class, in view of their close similarities in mode of action and chemical structure.
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| dailymed-drugs:59 |
BUSULFEX should be administered under the supervision of a qualified physician experienced in hematopoietic stem cell transplantation. Appropriate management of complications arising from its administration is possible only when adequate diagnostic and treatment facilities are readily available. The following warnings pertain to different physiologic effects of BUSULFEX in the setting of allogeneic transplantation. Hematologic:The most frequent serious consequence of treatment with BUSULFEX at the recommended dose and schedule is profound myelosuppression, occurring in all patients. Severe granulocytopenia, thrombocytopenia, anemia, or any combination thereof may develop. Frequent complete blood counts, including white blood cell differentials, and quantitative platelet counts should be monitored during treatment and until recovery is achieved. Absolute neutrophil counts dropped below 0.5x10/L at a median of 4 days post-transplant in 100% of patients treated in the BUSULFEX clinical trial. The absolute neutrophil count recovered at a median of 13 days following allogeneic transplantation when prophylactic G-CSF was used in the majority of patients. Thrombocytopenia (<25,000/mmor requiring platelet transfusion) occurred at a median of 5-6 days in 98% of patients. Anemia (hemoglobin<8.0 g/dL) occurred in 69% of patients. Antibiotic therapy and platelet and red blood cell support should be used when medically indicated. Neurological:Seizures have been reported in patients receiving highdose oral busulfan at doses producing plasma drug levels similar to those achieved following the recommended dosage of BUSULFEX. Despite prophylactic therapy with phenytoin, one seizure (1/42 patients) was reported during an autologous transplantation clinical trial of BUSULFEX. This episode occurred during the cyclophosphamide portion of the conditioning regimen, 36 hours afterthe last BUSULFEX dose. Anti-convulsant prophylactic therapy should be initiated prior to BUSULFEX treatment. Caution should be exercised when administering the recommended dose of BUSULFEX to patients with a history of a seizure disorder or head trauma or who are receiving other potentially epileptogenic drugs. Hepatic:Current literature suggests that high busulfan area under the plasma concentration verses time curve (AUC) values (>1,500��M���min) may be associated with an increased risk of developing hepatic venoocclusive disease (HVOD). Patients who have received prior radiation therapy, greater than or equal to three cycles of chemotherapy, or a prior progenitor cell transplant may be at an increased risk of developing HVOD with the recommended BUSULFEX dose and regimen. Based on clinical examination and laboratory findings, hepatic veno-occlusive disease was diagnosed in 8% (5/61) of patients treated with BUSULFEX in the setting of allogeneic transplantation, was fatalin 2/5 cases (40%), and yielded an overall mortality from HVOD in the entire study population of 2/61 (3%). Three of the five patients diagnosed with HVOD were retrospectively found to meet the Jones' criteria. The incidence of HVOD reported in the literature from the randomized, controlled trials (see CLINICAL STUDIES) was 7.7%-12%. Cardiac:Cardiac tamponade has been reported in pediatric patients with thalassemia (8/400 or 2% in one series) who received high doses of oral busulfan and cyclophosphamide as the preparatory regimen for hematopoietic progenitor cell transplantation. Six of the eight children died and two were saved by rapid pericardiocentesis. Abdominal pain and vomiting preceded the tamponade in most patients. No patients treated in the BUSULFEX (busulfan) Injection clinical trials experienced cardiac tamponade. Pulmonary:Bronchopulmonary dysplasia with pulmonary fibrosis is a rare but serious complication following chronic busulfan therapy. The average onset of symptoms is 4 years after therapy (range 4 months to 10 years).<br/>Carcinogenicity, Mutagenicity, Impairment of Fertility: Busulfan is a mutagen and a clastogen. In in vitro tests it caused mutations in Salmonella typhimuriumand Drosophila melanogaster. Chromosomal aberrations induced by busulfan have been reported in vivo(rats, mice, hamsters, and humans) and in vitro (rodent and human cells). The intravenous administration of busulfan (48 mg/kg given as biweekly doses of 12 mg/kg, or 30% of the total BUSULFEX dose on a mg/mbasis ) has been shown to increase the incidence of thymic and ovarian tumors in mice. Four cases of acute leukemia occurred among 19 patients who became pancytopenic in a 243 patient study incorporating busulfan as adjuvant therapy following surgical resection of bronchogenic carcinoma. Clinical appearance of leukemia was observed 5-8 years following oral busulfan treatment. Busulfan is a presumed human carcinogen. Ovarian suppression and amenorrhea commonly occur in premenopausal women undergoing chronic, low-dose busulfan therapy for chronic myelogenous leukemia. Busulfan depleted oocytes of female rats. Busulfan induced sterility in male rats and hamsters. Sterility, azoospermia and testicular atrophy have been reported in male patients. The solvent DMA may also impair fertility. A DMA daily dose of 0.45 g/kg/d given to rats for nine days (equivalent to 44% of the daily dose of DMA contained in the recommended dose of BUSULFEX on a mg/mbasis) significantly decreased spermatogenesis in rats. A single sc dose of 2.2 g/kg (27% of the total DMA dose contained in BUSULFEX on a mg/mbasis) four days after insemination terminated pregnancy in 100% of tested hamsters.<br/>Pregnancy: Busulfan may cause fetal harm when administered to a pregnant woman. Busulfan produced teratogenic changes in the offspring of mice, rats and rabbits when given during gestation. Malformations and anomalies included significant alterations in the musculoskeletal system, body weight gain, and size. In pregnant rats, busulfan produced sterility in both male and female offspring due to the absence of germinal cells in the testes and ovaries. The solvent, DMA, may also cause fetal harm when administered to a pregnant woman. In rats, DMA doses of 400 mg/kg/d (about 40% of the daily dose of DMA in the BUSULFEX dose on amg/mbasis) given during organogenesis caused significant developmental anomalies. The most striking abnormalities included anasarca, cleft palate, vertebral anomalies, rib anomalies, and serious anomalies of the vessels of the heart. There are no adequate and well-controlled studies of either busulfan or DMA in pregnant women. If BUSULFEX is used during pregnancy, or if the patient becomes pregnant while receiving BUSULFEX, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant.
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| dailymed-drugs:60 |
Intravenous use in eclampsia should be reserved for immediate
control of life-threatening convulsions. Parenteral
use in the presence of renal insufficiency may lead to magnesium intoxication.
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| dailymed-drugs:61 |
Clinical Worsening and Suicide Risk: Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trialsof antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18 to 24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older. The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4,400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1,000 patients treated)are provided in Table 1. No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide. It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression. All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms (see PRECAUTIONS and DOSAGE AND ADMINISTRATION, Discontinuation of Treatment withParoxetine Tablets, for a description of the risks of discontinuation of paroxetine tablets). Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers.Such monitoring should include daily observation by families and caregivers. Prescriptions for paroxetine tablets should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.<br/>Screening Patients for Bipolar Disorder: A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that paroxetine tablets are not approved for use in treating bipolar depression.<br/>Potential for Interaction With Monoamine Oxidase Inhibitors: In patients receiving another serotonin reuptake inhibitor drug in combination with a monoamine oxidase inhibitor (MAOI), there have been reports of serious, sometimes fatal, reactions including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma. These reactions have also been reported in patients who have recently discontinued that drug and have been started on an MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. While there are no human data showing such an interaction with paroxetine hydrochloride, limited animal data on the effects of combined use of paroxetine and MAOIs suggest that these drugs may act synergistically to elevate blood pressure and evoke behavioral excitation. Therefore, it is recommended that paroxetine tablets not be used in combination with an MAOI, or within 14 days of discontinuing treatment with an MAOI. At least 2 weeks should be allowed after stopping paroxetine tablets before starting an MAOI.<br/>Serotonin Syndrome: The development of a potentially life-threatening serotonin syndrome may occur with SNRIs and SSRIs, including paroxetine, particularly with concomitant use of serotonergic drugs (including triptans) and with drugs which impair metabolism of serotonin (including MAOIs). Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations,coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The concomitant use of paroxetine with MAOIs intended to treat depression is contraindicated (see CONTRAINDICATIONS and WARNINGS, Potential for Interaction With Monoamine Oxidase Inhibitors). If concomitant treatment with paroxetine with a 5-hydroxytryptamine receptor agonist (triptan) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases (see PRECAUTIONS, Drug Interactions). The concomitant use of paroxetine with serotonin precursors (such as tryptophan) is not recommended (see PRECAUTIONS, Drug Interactions).<br/>Potential Interaction With Thioridazine: Thioridazine administration alone produces prolongation of the QTc interval, which is associated with serious ventricular arrhythmias, such as torsade de pointes-type arrhythmias, and sudden death. This effect appears to be dose related. An in vivo study suggests that drugs which inhibit CYP2D6, such as paroxetine, will elevate plasma levels of thioridazine. Therefore, it is recommended that paroxetine not be used in combination with thioridazine (see CONTRAINDICATIONS and PRECAUTIONS).<br/>Usage In Pregnancy:
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| dailymed-drugs:63 |
Clinical Worsening and Suicide Risk: Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18-24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older. The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs. placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table 1. No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide. It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression. All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms (see PRECAUTIONS and DOSAGE AND ADMINISTRATION - Discontinuation of Treatment with Paroxetine, for a description of the risks of discontinuation of Paroxetine Hydrochloride Oral Suspension). Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers. Such monitoring should include daily observation by families and caregivers. Prescriptions for paroxetine should be written for the smallest quantity consistent with good patient management, in order to reduce the risk of overdose.<br/>Screening Patients for Bipolar Disorder: A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that paroxetine is not approved for use in treating bipolar depression.<br/>Potential for Interaction With Monoamine Oxidase Inhibitors: In patients receiving another serotonin reuptake inhibitor drug in combination with a monoamine oxidase inhibitor (MAOI), there have been reports of serious, sometimes fatal, reactions including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma. These reactions have also been reported in patients who have recently discontinued that drug and have been started on an MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. While there are no human data showing such an interaction with paroxetine, limited animal data on the effects of combined use of paroxetine and MAOIs suggest that these drugs may act synergistically to elevate blood pressure and evoke behavioral excitation. Therefore, it is recommended that paroxetine not be used in combination with an MAOI, or within 14 days of discontinuing treatment with an MAOI. At least 2 weeks should be allowed after stopping paroxetine before starting an MAOI.<br/>Serotonin Syndrome: The development of a potentially life-threatening serotonin syndrome may occur with use of paroxetine, particularly with concomitant use of serotonergic drugs (including triptans) and with drugs which impair metabolism of serotonin (including MAOIs). Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea,vomiting, diarrhea). The concomitant use of paroxetine with MAOIs intended to treat depression is contraindicated (see
CONTRAINDICATIONS and WARNINGS - Potential for Interaction With Monoamine Oxidase Inhibitors). If concomitant use of paroxetine with a 5-hydroxytryptamine receptor agonist (triptan) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases (see PRECAUTIONS - Drug Interactions). The concomitant use of paroxetine with serotonin precursors (such as tryptophan) is not recommended (see PRECAUTIONS - Drug Interactions).<br/>Potential Interaction With Thioridazine: Thioridazine administration alone produces prolongation of the QTc interval, which is associated with serious ventricular arrhythmias, such as torsade de pointes - type arrhythmias, and sudden death. This effect appears to be dose related. An
in vivo study
suggests that drugs which inhibit CYP2D6, such as paroxetine, will elevate plasma levels of thioridazine. Therefore, it is recommended that paroxetine not be used in combination with thioridazine (see CONTRAINDICATIONS and PRECAUTIONS).<br/>Usage in Pregnancy:<br/>Teratogenic Effects: Epidemiological studies have shown that infants born to women who had first trimester paroxetine exposure had an increased risk of cardiovascular malformations, primarily ventricular and atrial septal defects (VSDs and ASDs). In general, septal defects range from those that are symptomatic and may require surgery to those that are asymptomatic and may resolve spontaneously. If a patient becomes pregnant while taking paroxetine, she should be advised of the potential harm to the fetus. Unless the benefits of paroxetine to the mother justify continuing treatment, consideration should be given to either discontinuing paroxetine therapy or switching to another antidepressant (see PRECAUTIONS - Discontinuation of Treatment with Paroxetine
). For women who intend to become pregnant or are in their first trimester of pregnancy, paroxetine should only be initiated after consideration of the other available treatment options. A study based on Swedish national registry data evaluated infants of 6,896 women exposed to antidepressants in early pregnancy (5,123 women exposed to SSRIs; including 815 for paroxetine). Infants exposed to paroxetine in early pregnancy had an increased risk of cardiovascular malformations (primarily VSDs and ASDs) compared to the entire registry population (OR 1.8; 95% confidence interval 1.1-2.8). The rate of cardiovascular malformations following early pregnancy paroxetine exposure was2% vs. 1% in the entire registry population. Among the same paroxetine exposed infants, an examination of the data showed no increase in the overall risk for congenital malformations. A separate retrospective cohort study using US United Healthcare data evaluated 5,956 infants of mothers dispensed paroxetine or other antidepressants during the first trimester (n = 815 for paroxetine). This study showed a trend towards an increased risk for cardiovascular malformations for paroxetine compared to other antidepressants (OR 1.5; 95% confidence interval 0.8-2.9). The prevalence of cardiovascular malformations following first trimester dispensing was 1.5% for paroxetine vs. 1% for other antidepressants. Nine out of 12 infants with cardiovascular malformations whose mothers were dispensed paroxetine in the first trimester had VSDs. This study also suggested an increased risk of overall major congenital malformations (inclusive of the cardiovascular defects) for paroxetine compared to other antidepressants (OR 1.8; 95% confidence interval 1.2-2.8). The prevalence of all congenital malformations following first trimester exposure was 4% for paroxetine vs. 2% for other antidepressants.<br/>Animal Findings: Reproduction studies were performed at doses up to 50 mg/kg/day
in rats and 6 mg/kg/day in rabbits administered during organogenesis.
These doses are approximately 8 (rat) and 2 (rabbit) times the MRHD
on an mg/mbasis. These studies have revealed no evidence of teratogenic
effects. However, in rats, there was an increase in pup deaths during the
first 4 days of lactation when dosing occurred during the last trimester
of gestation and continued throughout lactation. This effect occurred at a
dose of 1 mg/kg/day or approximately one-sixth of the MRHD on an mg/mbasis.
The no-effect dose for rat pup mortality was not determined. The cause of
these deaths is not known.<br/>Nonteratogenic Effects: Neonates exposed to paroxetine and other SSRIs or serotonin and norepinephrine reuptake inhibitors (SNRIs), late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome (see WARNINGS - Potential for Interaction With Monoamine Oxidase Inhibitors). Infants exposed to SSRIs in late pregnancy may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). PPHN occurs in 1���2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality. In a retrospective case-control study of 377 women whose infants were born with PPHN and 836 women whose infants were born healthy, the risk for developing PPHN was approximately six-fold higher for infants exposed to SSRIs after the 20th week of gestation compared to infants who had not been exposed to antidepressants during pregnancy. There is currently no corroborative evidence regarding the risk for PPHN following exposure to SSRIs in pregnancy; this is the first study that has investigated the potential risk. The study did not include enough cases with exposure to individual SSRIs to determine if all SSRIs posed similar levels of PPHN risk. There have also been postmarketing reports of premature births in pregnant women exposed to paroxetine or other SSRIs. When treating a pregnant woman with paroxetine during the third trimester, the physician should carefully consider both the potential risks and benefits of treatment (see DOSAGE AND ADMINISTRATION). Physicians should note that in a prospective longitudinal study of 201 women with a history of major depression who were euthymic at the beginning of pregnancy, women who discontinued antidepressant medication during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressant medication.
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| dailymed-drugs:64 |
Heparin is not intended for intramuscular use. Hypersensitivity: Patients with documented
hypersensitivity to heparin should be given the drug only in clearly life-threatening
situations. Hemorrhage: Hemorrhage can occur at virtually any site in patients receiving
heparin. An unexplained fall in hematocrit, fall in blood pressure or any
other unexplained symptom should lead to serious consideration of a hemorrhagic
event. Heparin sodium should be used with extreme caution
in disease states in which there is increased danger of hemorrhage. Some of
the conditions in which increased danger of hemorrhage exists are: Cardiovascular���Subacute bacterial endocarditis. Severe hypertension. Surgical���During and immediately following (a) spinal tap or spinal anesthesia
or (b) major surgery, especially involving the brain, spinal cord or eye. Hematologic���Conditions associated with increased bleeding tendencies, such as
hemophilia, thrombocytopenia, and some vascular purpuras. Gastrointestinal���Ulcerative lesions and continuous tube drainage of the stomach or
small intestine. Other���Menstruation, liver
disease with impaired hemostasis. Coagulation
Testing: When heparin sodium is administered in therapeutic amounts,
its dosage should be regulated by frequent blood coagulation tests. If the
coagulation test is unduly prolonged or if hemorrhage occurs, heparin sodium
should be discontinued promptly (see OVERDOSAGE). Thrombocytopenia: Thrombocytopenia has
been reported to occur in patients receiving heparin with a reported incidence
of 0 to 30%. Mild thrombocytopenia (count greater than 100,000/mm)
may remain stable or reverse even if heparin is continued. However, thrombocytopenia
of any degree should be monitored closely. If the count falls below 100,000/mmor
if recurrent thrombosis develops (see White Clot Syndrome, PRECAUTIONS), the
heparin product should be discontinued. If continued heparin therapy is essential,
administration of heparin from a different organ source can be reinstituted
with caution. Solutions containing sodium ions should
be used with great care, if at all, in patients with congestive heart failure,
severe renal insufficiency and in clinical states in which there exists edema
with sodium retention. The intravenous administration
of these solutions can cause fluid and/or solute overloading resulting in
dilution of serum electrolyte concentrations, overhydration, congested states
or pulmonary edema. The risk of dilutional states is
inversely proportional to the electrolyte concentrations of administered parenteral
solutions. The risk of solute overload causing congested states with peripheral
and pulmonary edema is directly proportional to the electrolyte concentrations
of such solutions. In patients with diminished renal
function, administration of solutions containing sodium ions may result in
sodium retention. Excessive administration of potassium-free
solutions may result in significant hypokalemia. As
the dosage of solutions of heparin sodium must be titrated to individual patient
response, additive medications should not be delivered via this solution.
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| dailymed-drugs:66 |
Additives may be incompatible. Consult with pharmacist, if
available. When introducing additives, use aseptic techniques. Mix thoroughly.
Do not store. Because of the potential for life-threatening
events, caution should be taken to ensure that precipitates have not formed
in any parenteral nutrient admixture. This product contains
sodium hydrosulfite, a form of sulfite that may cause allergic-type reactions
including anaphylactic symptoms and life-threatening or less severe asthmatic
episodes in certain susceptible people. The overall prevalence of sulfite
sensitivity in the general population is unknown and probably low. Sulfite
sensitivity is seen more frequently in asthmatic than in nonasthmatic people. Safe,
effective use of parenteral nutrition requires a knowledge of nutrition as
well as clinical expertise in recognition and treatment of the complicationswhich can occur. FREQUENT EVALUATIONS AND LABORATORY DETERMINATIONS ARE NECESSARY
FOR PROPER MONITORING OF PARENTERAL NUTRITION. Studies should include blood
sugar, serum proteins, kidney and liver function tests, electrolytes, hemogram,
carbon dioxide content, serum osmolarities, blood cultures, and blood ammonia
levels. Administration of amino acids in the presence
of impaired renal function or gastrointestinal bleeding may augment an already
elevated blood urea nitrogen. Patients with azotemia from any cause should
not be infused with amino acids without regard to total nitrogen intake. Administration
of intravenous solutions can cause fluid and/or solute overload resulting
in dilution of serum electrolyte concentrations, over-hydration, congested
states, or pulmonary edema. The risk of dilutional states is inversely proportional
to the electrolyte concentrations of the solutions. The risk of solute overload
causing congested states with peripheral and pulmonary edema is directly proportional
to the electrolyte concentrations of the solutions. WARNING:
This product contains aluminum that may be toxic. Aluminum may reach toxic
levels with prolonged parenteral administration if kidney function is impaired.
Premature neonates are particularly at risk because their kidneys are immature,
and they require large amounts of calcium and phosphate solutions, which contain
aluminum. Research indicates that patients with impaired
kidney function, including premature neonates, who receive parenteral levels
of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels
associated with central nervous system and bone toxicity. Tissue loading may
occur at even lower rates of administration.
|
| dailymed-drugs:70 |
Maximum daily dose should not exceed 5 mg/kg/day (2.3 mg/lb)
with normal renal function. Transient neurological disturbances
may occur. These include circumoral paresthesia or numbness, tingling or formication
of the extremities, generalized pruritus, vertigo, dizziness, and slurring
of speech. For these reasons, patients should be warned not to drive vehicles
or use hazardous machinery while on therapy. Reduction of dosage may alleviate
symptoms. Therapy need not be discontinued, but such patients should be observed
with particular care. Nephrotoxicity can occur and is
probably a dose-dependent effect of colistimethate sodium. These manifestations
of nephrotoxicity are reversible following discontinuation of the antibiotic. Overdosage
can result in renal insufficiency, muscle weakness, and apnea .
See PRECAUTIONS,
Drug Interactions subsection for use concomitantly with
other antibiotics and curariform drugs. Respiratory
arrest has been reported following intramuscular administration of colistimethate
sodium. Impaired renal function increases the possibility of apnea and neuromuscular
blockade following administration of colistimethate sodium. Therefore, it
is important to follow recommended dosing guidelines. See DOSAGE AND ADMINISTRATION section for use in renal impairment. Pseudomembranous colitis has been reported with nearly all
antimicrobial agents, and may range in severity from mild to life-threatening.
Therefore, it is important to consider this diagnosis in patients who present
with diarrhea subsequent to the administration of antibacterial agents. Treatment
with antibacterial agents alters the normal flora of the colon and may permit
overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is a primary cause of���antibiotic-associated colitis.��� After
the diagnosis of pseudomembranous colitis has been established, appropriate
therapeutic measures should be initiated. Mild cases of pseudomembranous colitis
usually respond to drug discontinuation alone. In moderate-to-severe cases,
consideration should be given to management with fluids and electrolytes,
protein supplementation, and treatment with an antibacterial drug clinically
effective against Clostridium difficile colitis.
|
| dailymed-drugs:71 |
Clinical Worsening and Suicide Risk: Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18-24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older. The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table 1. No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide. It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression. All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms . Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers. Such monitoring should include daily observation by families and caregivers. Prescriptions for citalopram should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose. Screening Patients for Bipolar Disorder: A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that citalopram is not approved for use in treating bipolar depression.<br/>Potential for Interaction with Monoamine Oxidase Inhibitors: In patients receiving serotonin reuptake inhibitor drugs in combination with a monoamine oxidase inhibitor (MAOI), there have been reports of serious, sometimes fatal, reactions including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma. These reactions have also been reported in patients who have recently discontinued SSRI treatment and have been started on an MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. Furthermore, limited animal data on the effects of combined use of SSRIs and MAOIs suggest that these drugs may act synergistically to elevate blood pressure and evoke behavioral excitation. Therefore, it is recommended that citalopram HBr should not be used in combination with an MAOI, or within 14 days of discontinuing treatment with an MAOI. Similarly, at least 14 days should be allowed after stopping citalopram HBr before starting an MAOI.<br/>Serotonin Syndrome:: The development of a potentially life-threatening serotonin syndrome may occur with SNRIs and SSRIs, including citalopram treatment, particularly with concomitant use of serotonergic drugs (including triptans) and with drugs which impair metabolism of serotonin (including MAOIs). Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The concomitant use of citalopram with MAOIs intended to treat depression is contraindicated If concomitant treatment of citalopram with a 5-hydroxytryptamine receptor agonist (triptan) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases . The concomitant use of citalopram with serotonin precursors (such as tryptophan) is not recommended .
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| dailymed-drugs:72 |
PROMETHAZINE HCl SUPPOSITORIES SHOULD NOT BE USED IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE BECAUSE OF THE POTENTIAL FOR FATAL RESPIRATORY DEPRESSION. POSTMARKETING CASES OF RESPIRATORY DEPRESSION, INCLUDING FATALITIES, HAVE BEEN REPORTED WITH USE OF PROMETHAZINE HCl SUPPOSITORIES IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE. A WIDE RANGE OF WEIGHT-BASED DOSES OF PROMETHAZINE HCl SUPPOSITORIES HAVE RESULTED IN RESPIRATORY DEPRESSION IN THESE PATIENTS. CAUTION SHOULD BE EXERCISED WHEN ADMINISTERING PROMETHAZINE HCl SUPPOSITORIES TO PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER. IT IS RECOMMENDED THAT THE LOWEST EFFECTIVE DOSE OF PROMETHAZINE HCl SUPPOSITORIES BE USED IN PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER AND CONCOMITANT ADMINISTRATION OF OTHER DRUGS WITH RESPIRATORY DEPRESSANT EFFECTS BE AVOIDED.<br/>CNS Depression: Promethazine HCl suppositories may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a vehicle or operating machinery. The impairment may be amplified by concomitant use of other central-nervous-system depressants such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore such agents should either be eliminated or given in reduced dosage in the presence of promethazine HCl .<br/>Respiratory Depression: Promethazine HCl suppositories may lead to potentially fatal respiratory depression. Use of promethazine HCl suppositories in patients with compromised respiratory function (e.g., COPD, sleep apnea) should be avoided.<br/>Lower Seizure Threshold: Promethazine HCl suppositories may lower seizure threshold. It should be used with caution in persons with seizure disorders or in persons who are using concomitant medications, such as narcotics or local anesthetics, which may also affect seizure threshold.<br/>Bone-marrow Depression: Promethazine HCl suppositories should be used with caution in patients with bone-marrow depression. Leukopenia and agranulocytosis have been reported, usually when promethazine HCl has been used in association with other known marrow-toxic agents.<br/>Neuroleptic Malignant Syndrome: A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with promethazine HCl alone or in combination with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse orblood pressure, tachycardia, diaphoresis and cardiac dysrhythmias). The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergictoxicity, heat stroke, drug fever and primary central nervous system (CNS) pathology. The management of NMS should include 1) immediate discontinuation of promethazine HCl, antipsychotic drugs, if any, and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS. Since recurrences of NMS have been reported with phenothiazines, the reintroduction of promethazine HCl should be carefully considered.<br/>Use in Pediatric Patients: PROMETHAZINE HCl SUPPOSITORIES ARE CONTRAINDICATED FOR USE IN PEDIACTRIC PATIENTS LESS THAN TWO YEARS OF AGE. CAUTION SHOULD BE EXERCISED WHEN ADMINISTERING PROMETHAZINE HCl SUPPOSITORIES TO PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER BECAUSE OF THE POTENTIAL FOR FATAL RESPIRATORY DEPRESSION. RESPIRATORY DEPRESSION AND APNEA, SOMETIMES ASSOCIATED WITH DEATH, ARE STRONGLY ASSOCIATED WITH PROMETHAZINE PRODUCTS AND ARE NOT DIRECTLY RELATED TO INDIVIDUALIZED WEIGHT-BASED DOSING, WHICH MIGHT OTHERWISE PERMIT SAFE ADMINISTRATION. CONCOMITANT ADMINISTRATION OF PROMETHAZINE PRODUCTS WITH OTHER RESPIRATORY DEPRESSANTS HAS AN ASSOCIATION WITH RESPIRATORY DEPRESSION, AND SOMETIMES DEATH, IN PEDIATRIC PATIENTS. ANTIEMETRICS ARE NOT RECOMMENDED FOR TREATMENT OF UNCOMPLICATED VOMITING IN PEDIATRIC PATIENTS, AND THEIR USE SHOULD BE LIMITED TO PROLONGED VOMITING OF KNOWN ETIOLOGY. THE EXTRAPYRAMIDAL SYMPTOMS WHICH CAN OCCUR SECONDARY TO PROMETHAZINE HCl SUPPOSITORIES ADMINISTRATION MAY BE CONFUSED WITH THE CNS SIGNS OF UNDIAGNOSED PRIMARY DISEASE,e.g., ENCEPHALOPATHY OR REYE'S SYNDROME. THE USE OF PROMETHAZINE HCl SUPPOSITORIES SHOULD BE AVOIDED IN PEDIATRIC PATIENTS WHOSE SIGNS AND SYMPTOMS MAY SUGGEST REYE'S SYNDROME OR OTHER HEPATIC DISEASES. Excessively large dosages of antihistamines, including promethazine HCl suppositories, in pediatric patients may cause sudden death . Hallucinations and convulsions have occurred with therapeutic doses and overdoses of promethazine HCl in pediatric patients. In pediatric patients who are acutely ill associated with dehydration, there is an increased susceptibility to dystonias with the use of promethazine HCl.<br/>Other Considerations: Administration of promethazine HCl has been associated with reported cholestatic jaundice.
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| dailymed-drugs:73 |
For single-dose intraocular use only. Discard unused portion. Intraocular carbachol 0.01% should be used with caution in patients with acute cardiac failure, bronchial asthma, peptic ulcer, hyperthyroidism, G.I. spasm, urinary tract obstruction and Parkinson's disease.
|
| dailymed-drugs:75 |
The use of Trecator alone in the treatment of tuberculosis
results in rapid development of resistance. It is essential, therefore,
to give a suitable companion drug or drugs, the choice being based
on the results of susceptibility testing. However, therapy may be
initiated prior to receiving the results of susceptibility tests as
deemed appropriate by the physician. Ethionamide should be administered
with at least one, sometimes two, other drugs to which the organism
is known to be susceptible . Drugs which
have been used as companion agents are rifampin, ethambutol, pyrazinamide,
cycloserine, kanamycin, streptomycin, and isoniazid. The usual warnings,
precautions, and dosage regimens for these companion drugs should
be observed. Patient compliance is essential
to the success of the antituberculosis therapy and to prevent the
emergence of drug-resistant organisms. Therefore, patients should
adhere to the drug regimen for the full duration of treatment. It
is recommended that directly observed therapy be practiced when patients
are receiving antituberculous medication. Additional consultation
from experts in the treatment of drug-resistant tuberculosis is recommended
when patients develop drug-resistant organisms.
|
| dailymed-drugs:77 |
Desoximetasone Gel USP, 0.05% is not for ophthalmic use. Keep out of reach of children.
|
| dailymed-drugs:80 |
Hyponatremia: Clinically significant hyponatremia (sodium<125 mmol/L) can develop during oxcarbazepine use. In the 14 controlled epilepsy studies 2.5% of oxcarbazepine-treated patients (38/1,524) had a sodium of less than 125 mmol/L at some point during treatment, compared to no such patients assigned placebo or active control (carbamazepine and phenobarbital for adjunctive and monotherapy substitution studies, and phenytoin and valproate for the monotherapy initiation studies). Clinically significant hyponatremia generally occurred during the first three months of treatment with oxcarbazepine, although there were patients who first developed a serum sodium<125 mmol/L more than one year after initiation of therapy. Most patients who developed hyponatremia were asymptomatic but patients in the clinical trials were frequently monitored and some had their oxcarbazepine dose reduced, discontinued, or had their fluid intake restricted for hyponatremia. Whether or not these maneuvers prevented the occurrence of more severe events is unknown. Cases of symptomatic hyponatremia have been reported during postmarketing use. In clinical trials, patients whose treatment with oxcarbazepine was discontinued due to hyponatremia generally experienced normalization of serum sodium within a few days without additional treatment. Measurement of serum sodium levels should be considered for patients during maintenance treatment with oxcarbazepine, particularly if the patient is receiving other medications known to decrease serum sodium levels (for example, drugs associated with inappropriate ADH secretion) or if symptoms possibly indicating hyponatremia develop (e.g., nausea, malaise, headache, lethargy, confusion, obtundation, or increase in seizure frequency or severity).<br/>Anaphylactic Reactions and Angioedema: Rare cases of anaphylaxis and angioedema involving the larynx, glottis, lips and eyelids have been reported in patients after taking the first or subsequent doses of oxcarbazepine. Angioedema associated with laryngeal edema can be fatal. If a patient develops any of these reactions after treatment with oxcarbazepine, the drug should be discontinued and an alternative treatment started. These patients should not be rechallenged with the drug (see WARNINGS, Patients with a Past History of Hypersensitivity Reaction to Carbamazepine).<br/>Patients with a Past History of Hypersensitivity Reaction to Carbamazepine: Patients who have had hypersensitivity reactions to carbamazepine should be informed that approximately 25% to 30% of them will experience hypersensitivity reactions with oxcarbazepine. For this reason patients should be specifically questioned about any prior experience with carbamazepine, and patients with a history of hypersensitivity reactions to carbamazepine should ordinarily be treated with oxcarbazepine only if the potential benefit justifies the potential risk. If signs or symptoms of hypersensitivity develop, oxcarbazepine should be discontinued immediately (see WARNINGS, Anaphylactic Reactions and Angioedemaand PRECAUTIONS, Multi-Organ Hypersensitivity).<br/>Serious Dermatological Reactions: Serious dermatological reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in both children and adults in association with oxcarbazepine use. The median time of onset for reported cases was 19 days. Such serious skin reactions may be life threatening, and some patients have required hospitalization with very rare reports of fatal outcome. Recurrence of the serious skin reactions following rechallenge with oxcarbazepine has also been reported. The reporting rate of TEN and SJS associated with oxcarbazepine use, which is generally accepted to be an underestimate due to underreporting, exceeds the background incidence rate estimates by a factor of 3 to 10 fold. Estimates of the background incidence rate for these serious skin reactions in the general population range between 0.5 to 6 cases per million-person years. Therefore, if a patient develops a skin reaction while taking oxcarbazepine, consideration should be given to discontinuing oxcarbazepine use and prescribing another antiepileptic medication.<br/>Withdrawal of AEDs: As with all antiepileptic drugs, oxcarbazepine should be withdrawn gradually to minimize the potential of increased seizure frequency.
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| dailymed-drugs:85 |
Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. There have been reportsof individuals with a history of penicillin hypersensitivity who have experienced severe reactions when treated with cephalosporins. Before initiating therapy with any penicillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillin, cephalosporins, and other allergens. If an allergic reaction occurs, the drug should be discontinued and the appropriate therapy instituted. Serious anaphylactoid reactions require immediate emergency treatment with epinephrine. Oxygen, intravenous steroids, and airway management���including intubation, should be administered as indicated.
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| dailymed-drugs:87 |
Clinical Worsening and Suicide Risk: Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18 to 24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged65 and older. The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table 1. No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide. It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression. All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers.Such monitoring should include daily observation by families and caregivers. Prescriptions for ClomiPRAMINE hydrochloride capsules should be written for the smallest quantity of capsules consistent with good patient management, in order to reduce the risk of overdose.<br/>Screening Patients for Bipolar Disorder: A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that ClomiPRAMINE hydrochloride capsules are not approved for use in treating bipolar depression.<br/>Seizures: During premarket evaluation, seizure was identified as the most significant risk of ClomiPRAMINE hydrochloride use. The observed cumulative incidence of seizures among patients exposed to ClomiPRAMINE hydrochloride at doses up to 300 mg/day was 0.64% at 90 days, 1.12% at 180 days, and 1.45% at 365 days. The cumulative rates correct the crude rate of 0.7%, (25 of 3519 patients) for the variable duration of exposure in clinical trials. Although dose appears to be a predictor of seizure, there is a confounding of dose and duration of exposure, making it difficult to assess independently the effect of either factor alone. The ability to predict the occurrence of seizures in subjects exposed to doses of ClomiPRAMINE hydrochloride greater than 250 mg is limited, given that the plasma concentration of ClomiPRAMINE may be dose-dependent and may vary among subjects given the same dose. Nevertheless, prescribers are advised to limit the daily dose to a maximum of 250 mg in adults and 3 mg/kg (or 200 mg) in children and adolescents (see DOSAGE AND ADMINISTRATION). Caution should be used in administering ClomiPRAMINE to patients with a history of seizures or other predisposing factors, e.g., brain damage of varying etiology, alcoholism, and concomitant use with other drugs that lower the seizure threshold. Rare reports of fatalities in association with seizures have been reported by foreign postmarketing surveillance, but not in U.S. clinical trials. In some of these cases, ClomiPRAMINE had been administered with other epileptogenic agents; in others, the patients involved had possibly predisposing medical conditions. Thus a causal association between ClomiPRAMINE treatment and these fatalities has not been established. Physicians should discuss with patients the risk of taking ClomiPRAMINE while engaging in activities in which sudden loss of consciousness could result in serious injury to the patient or others, e.g., the operation of complex machinery, driving, swimming, climbing.
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| dailymed-drugs:88 |
Gastrointestinal Effects: In the collaborative study, major gastrointestinal bleeding was no more common in those neonates receiving indomethacin than in those neonates on placebo. However, minor gastrointestinal bleeding (i.e., chemical detection of blood in the stool) was more commonly noted in those neonates treated with indomethacin. Severe gastrointestinal effects have been reported in adults with various arthritic disorders treated chronically with oral indomethacin. [For further information, see package insert for Capsules INDOCIN(Indomethacin).]<br/>Central Nervous System Effects: Prematurity per se, is associated with an increased incidence of spontaneous intraventricular hemorrhage. Because indomethacin may inhibit platelet aggregation, the potential for intraventricular bleeding may be increased. However, in the large multicenter study of INDOCIN I.V. , the incidence of intraventricular hemorrhage in neonates treated with INDOCIN I.V. was not significantly higher than in the control neonates.<br/>Renal Effects: INDOCIN I.V. may cause significant reduction in urine output (50 percent or more) with concomitant elevations of blood urea nitrogen and creatinine, and reductions in glomerular filtration rate and creatinine clearance. These effects in most neonates are transient, disappearing with cessation of therapy with INDOCIN I.V. However, because adequate renal function can depend upon renal prostaglandin synthesis, INDOCIN I.V. may precipitate renal insufficiency, including acute renal failure, especially in neonates with other conditions that may adversely affect renal function (e.g., extracellular volume depletion from any cause, congestive heart failure, sepsis, concomitant use of any nephrotoxic drug, hepatic dysfunction). When significant suppression of urine volume occurs after a dose of INDOCIN I.V., no additional dose should be given until the urine output returns to normal levels. INDOCIN I.V. in pre-term infants may suppress water excretion to a greater extent than sodium excretion. When this occurs, a significant reduction in serum sodium values (i.e., hyponatremia) may result. Neonates should have serum electrolyte determinations done during therapy with INDOCIN I.V. Renal function and serum electrolytes should be monitored .
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| dailymed-drugs:89 |
Caution should be exercised when administering Tigan to children for
the treatment of vomiting. Antiemetics are not recommended for treatment
of uncomplicated vomiting in children and their use should be limited
to prolonged vomiting of known etiology. There are two principal reasons
for caution: Tigan may produce drowsiness. Patients should not operate motor
vehicles or other dangerous machinery until their individual responses
have been determined.<br/>Usage in Pregnancy:: Trimethobenzamide hydrochloride was studied in reproduction
experiments in rats and rabbits and no teratogenicity was suggested.
The only effects observed were an increased percentage of embryonic
resorptions or stillborn pups in rats administered 20 mg and 100 mg/kg
and increased resorptions in rabbits receiving 100 mg/kg. In each
study these adverse effects were attributed to one or two dams. The
relevance to humans is not known. Since there is no adequate experience
in pregnant or lactating women who have received this drug, safety
in pregnancy or in nursing mothers has not been established.<br/>Usage with Alcohol:: Concomitant use of alcohol with Tigan may result in
an adverse drug interaction.
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| dailymed-drugs:90 |
Increased Mortality in Elderly Patients with Dementia-Related Psychosis: Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. SEROQUEL (quetiapine) is not approved for the treatment of patients with dementia-related psychosis (see Boxed Warning).<br/>Clinical Worsening and Suicide Risk: Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressantdrugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18-24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older. The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table 1. No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide. It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression. All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers. Such monitoring should include daily observation by families and caregivers. Prescriptions for SEROQUEL should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose. Screening Patients for Bipolar Disorder: A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that SEROQUEL is approved for use in treating adult bipolar depression.<br/>Neuroleptic Malignant Syndrome (NMS): A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with administration of antipsychotic drugs, including SEROQUEL. Rare cases of NMS have been reported with SEROQUEL. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis) and acute renal failure. The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to exclude cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations inthe differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever and primary central nervous system (CNS) pathology. The management of NMS should include: 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy; 2) intensive symptomatic treatment and medical monitoring; and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement aboutspecific pharmacological treatment regimens for NMS. If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored since recurrences of NMS have been reported.<br/>Tardive Dyskinesia: A syndrome of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of antipsychotic treatment, which patients are likely to develop the syndrome. Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown. The risk of developing tardive dyskinesia and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses. There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn. Antipsychotic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown. Given these considerations, SEROQUEL should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychotic treatment should generally be reserved for patients who appear to suffer from a chronic illness that (1) is known to respond to antipsychotic drugs, and (2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically. If signs and symptoms of tardive dyskinesia appear in a patient on SEROQUEL, drug discontinuation should be considered. However, some patients may require treatment with SEROQUEL despite the presence of the syndrome.<br/>Hyperglycemia and Diabetes Mellitus: Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics, including Seroquel . Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. Given these confounders, the relationship between atypical antipsychotic use and hyperglycemia-related adverse events is not completely understood. However, epidemiological studies suggest an increased risk of treatment-emergent hyperglycemia-related adverse events in patients treated with the atypical antipsychotics. Precise risk estimates for hyperglycemia-related adverse events in patients treated with atypical antipsychotics are not available. Patients with an established diagnosis of diabetes mellitus who are started on atypical antipsychotics should be monitored regularly for worsening of glucose control. Patients with risk factors for diabetes mellitus (eg, obesity, family history of diabetes) who are starting treatment with atypical antipsychotics should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the suspect drug.
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| dailymed-drugs:93 |
In case of life-threatening, serious or overwhelming malaria infections due to P. falciparum, patients should be treated with an intravenous antimalarial drug. Following completion of intravenous treatment, mefloquine may be given to complete the course of therapy. Data on the use of halofantrine subsequent to administration of mefloquine suggests a significant, potentially fatal prolongation of the QTc interval of the ECG. Therefore, halofantrine must not be given simultaneously with or subsequent to mefloquine. No data are available on the use of mefloquine after halofantrine . Mefloquine may cause psychiatric symptoms in a number of patients, ranging from anxiety, paranoia, and depression to hallucinations and psychotic behavior. On occasions, these symptoms have been reported to continue long after mefloquine has been stopped. Rare cases of suicidal ideation and suicide have been reported though no relationship to drug administration has been confirmed. To minimize the chances of these adverse events, mefloquine should not be taken for prophylaxis in patients with active depression or with a recent history of depression, generalized anxiety disorder, psychosis, or schizophrenia or other major psychiatric disorders. Mefloquine should be used with caution in patients with a previous history of depression. During prophylactic use, if psychiatric symptoms such as acute anxiety, depression, restlessness or confusion occur, these may be considered prodromal to a more serious event. In these cases, the drug must be discontinued and an alternative medication should be substituted. Concomitant administration of mefloquine and quinine or quinidine may produce electrocardiographic abnormalities. Concomitant administration of mefloquine and quinine or chloroquine may increase the risk of convulsions.
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| dailymed-drugs:94 |
ARIXTRA Injection is not intended for intramuscular
administration. ARIXTRA cannot be used
interchangeably (unit for unit) with heparin, low molecular weight
heparins or heparinoids, as they differ in manufacturing process,
anti-Xa and anti-IIa activity, units, and dosage. Each of these medicines
has its own instructions for use.<br/>Renal Impairment (See also
CONTRAINDICATIONS):<br/>Hip Fracture, Hip Replacement
and Knee Replacement Surgeries: Major bleeding in patients receiving prophylactic
therapy in hip fracture, hip replacement, or knee replacement surgery
occurred in 1.6% (25/1,565) of patients with normal renal function,
in 2.4% (31/1,288) with mild renal impairment, in 3.8% (19/504) with
moderate renal impairment, and in 4.8% (4/83) with severe renal impairment.
When ARIXTRA was used according to the recommended timing of the first
injection (6 to 8 hours after surgery), major bleeding occurred
in 1.8% (16/905) of patients with normal renal function, in 2.2% (15/675)with mild renal impairment, in 2.3% (6/265) with moderate renal impairment,
and in 0% (0/40) with severe renal impairment.<br/>Abdominal Surgery: Major bleeding in patients receiving prophylactic
therapy in abdominal surgery occurred in 2.1% (13/606) of patients
with normal renal function, in 3.6% (22/613) with mild renal impairment,
in 6.7% (12/179) with moderate renal impairment, and in 7.1% (1/14)
with severe renal impairment. When ARIXTRA was used according to the
recommended timing of the first injection (6 to 8 hours after
surgery), major bleeding occurred in 2.1% (10/467) of patients with
normal renal function, in 3.3% (16/481) with mild renal impairment,
in 5.8% (8/137) with moderate renal impairment, and in 7.7%(1/13)
with severe renal impairment.<br/>Treatment of Deep Vein Thrombosis
and Pulmonary Embolism: Major bleeding in patients receiving treatment for
DVT and PE occurred in 0.4% (4/1,132) of patients with normal renal
function, in 1.6% (12/733) with mild renal impairment, in 2.2% (7/318)
with moderate renal impairment, and in 7.3% (4/55) with severe renal
impairment. ARIXTRA should be used with
caution in patients with moderate renal impairment (creatinine clearance
30-50 mL/min). (See CLINICAL PHARMACOLOGY: Special Populations,
Renal Impairment.) Renal function should
be assessed periodically in patients receiving ARIXTRA. The drug should
be discontinued immediately in patients who develop severe renal impairment
while on therapy. After discontinuation of ARIXTRA, its anticoagulant
effects may persist for 2-4 days in patients with normal renal
function (i.e., at least 3-5 half-lives). The anticoagulant effects
of ARIXTRA may persist even longer in patients with renal impairment
(see CLINICAL PHARMACOLOGY).<br/>Hemorrhage: ARIXTRA Injection, like other anticoagulants, should
be used with extreme caution in conditions with increased risk of
hemorrhage, such as congenital or acquired bleeding disorders, active
ulcerative and angiodysplastic gastrointestinal disease, hemorrhagic
stroke, or shortly after brain, spinal, or ophthalmological surgery,
or in patients treated concomitantly with platelet inhibitors.<br/>Laboratory Testing: Because routine coagulation tests such as Prothrombin
Time (PT) and Activated Partial Thromboplastin Time (aPTT) are relatively
insensitive measures of the activity of ARIXTRA and international
standards of heparin or LMWH are not calibrators to measure anti-Factor
Xa activity of ARIXTRA, if during therapy with ARIXTRA, unexpected
changes in coagulation parameters or major bleeding occurs, ARIXTRA
should be discontinued (see PRECAUTIONS: Laboratory Tests).<br/>Neuraxial Anesthesia and Post-operative
Indwelling Epidural Catheter Use: Spinal or epidural hematomas, which may result in
long-term or permanent paralysis, can occur with the use of anticoagulants
and neuraxial (spinal/epidural) anesthesia or spinal puncture. The
risk of these events may be higher with post-operative use of indwelling
epidural catheters or concomitant use of other drugs affecting hemostasis
such as NSAIDs (see Boxed Warning for Spinal/Epidural Hematomas).
In spontaneous post-marketing reports, there have been several cases
of epidural or spinal hematoma that have occurred in association with
the use of ARIXTRA by SC injection.<br/>Thrombocytopenia: Thrombocytopenia can occur with the administration
of ARIXTRA. Moderate thrombocytopenia (platelet counts between 100,000/mmand 50,000/mm) occurred at a rate of 3.0% in
patients given ARIXTRA 2.5 mg in the peri-operative hip fracture,
hip replacement or knee replacement surgery, and abdominal surgery
clinical trials. Severe thrombocytopenia (platelet counts less than
50,000/mm) occurred at a rate of 0.2% in patients given
ARIXTRA 2.5 mg in these clinical trials. During extended prophylaxis,
no cases of moderate or severe thrombocytopenia were reported. Moderate thrombocytopenia occurred at a rate of 0.5%
in patients given the ARIXTRA treatment regimen in the DVT and PE
treatment clinical trials. Severe thrombocytopenia occurred at a rate
of 0.04% in patients given the ARIXTRA treatment regimen in the DVT
and PE treatment clinical trials. Thrombocytopenia
of any degree should be monitored closely. If the platelet count falls
below 100,000/mm, ARIXTRA should be discontinued.
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| dailymed-drugs:95 |
Danger signs of possible gold toxicity include fall in hemoglobin, leukopenia below 4,000 WBC/cu mm, granulocytes below 1,500/cu mm, decrease in platelets below 150,000/cu mm, proteinuria, hematuria, pruritus, rash, stomatitis or persistent diarrhea. Thrombocytopenia has occurred in 1���3% of patients treated with Ridaura (auranofin), some of whom developed bleeding. The thrombocytopenia usually appears to be peripheral in origin and is usually reversible upon withdrawal of Ridaura. Its onset bears no relationship to the duration of Ridaura therapy and its course may be rapid. While patients' platelet counts should normally be monitored at least monthly , the occurrence of a precipitous decline in platelets or a platelet count less than 100,000/cu mm or signs and symptoms (e.g., purpura, ecchymoses or petechiae) suggestive of thrombocytopenia indicates a need to immediately withdraw Ridaura and other therapies with the potential to cause thrombocytopenia, and to obtain additional platelet counts. No additional Ridaura should be given unless the thrombocytopenia resolves and further studies show it was not due to gold therapy. Proteinuria has developed in 3-9% of patients treated with Ridaura. If clinically significant proteinuria or microscopic hematuria is found , Ridaura and other therapies with the potential to cause proteinuria or microscopic hematuria should be stopped immediately.
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| dailymed-drugs:96 |
Immediate hypersensitivity reactions may occur after administration of ipratropium bromide, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, and oropharyngeal edema.
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| dailymed-drugs:97 |
1. Volume and electrolyte depletion. The dose of bumetanide should be adjusted to the patient's need. Excessive doses or too frequent administration can lead to profound water loss, electrolyte depletion, dehydration, reduction in blood volume and circulatory collapse with the possibility of vascular thrombosis and embolism, particularly in elderly patients. 2. Hypokalemia. Hypokalemia can occur as a consequence of bumetanide administration. Prevention of hypokalemia requires particular attention in the following conditions: patients receiving digitalis and diuretics for congestive heart failure, hepatic cirrhosis and ascites, states of aldosterone excess with normal renal function, potassium-losing nephropathy, certain diarrheal states, or other states where hypokalemia is thought to represent particular added risks to the patient, i.e., history of ventricular arrhythmias. In patients with hepatic cirrhosis and ascites, sudden alterations of electrolyte balance may precipitate hepatic encephalopathy and coma. Treatment in such patients is best initiated in the hospital with small doses and careful monitoring of the patient's clinical status and electrolyte balance. Supplemental potassium and/or spironolactone may prevent hypokalemia and metabolic alkalosis in these patients. 3. Ototoxicity. In cats, dogs and guinea pigs, bumetanide has been shown to produce ototoxicity. In these test animals bumetanide was 5 to 6 times more potent than furosemide and, since the diuretic potency of bumetanide is about 40 to 60 times furosemide, it is anticipated that blood levels necessary to produce ototoxicity will rarely be achieved. The potential exists, however, and must be considered a risk of intravenous therapy, especially at high doses, repeated frequently in the face of renal excretory function impairment. Potentiation of aminoglycoside ototoxicity has not been tested for bumetanide. Like other members of this class of diuretics, bumetanide probably shares this risk. 4. Allergy to sulfonamides. Patients allergic to sulfonamides may show hypersensitivity to bumetanide. 5. Thrombocytopenia. Since there have been rare spontaneous reports of thrombocytopenia from postmarketing experience, patients should be observed regularly for possible occurrence of thrombocytopenia.
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| dailymed-drugs:98 |
In a few patients hydralazine may produce a clinical picture simulating systemic lupus erythematosus including glomerulonephritis. In such patients hydralazine should be discontinued unless the benefit-to-risk determination requires continued antihypertensive therapy with this drug. Symptoms and signs usually regress when the drug is discontinued but residua have been detected many years later. Long-term treatment with steroids may be necessary. (See PRECAUTIONS,Laboratory Tests.)
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| dailymed-drugs:102 |
Potassium Chloride
in Lactated Ringer's and 5% Dextrose Injection, USP should be used with
great care, if at all, in patients with congestive heart failure, severe
renal insufficiency, and in clinical states in which there exists edema with sodium retention. Potassium Chloride
in Lactated Ringer's and 5% Dextrose Injection, USP should be used with
great care, if at all, in patients with hyperkalemia, severe renal
failure, and in conditions in which potassium retention is present. Potassium Chloride
in Lactated Ringer's and 5% Dextrose Injection, USP should be used with
great care in patients with metabolic or respiratory alkalosis. The
administration of lactate ions should be done with great care in those
conditions in which there is an increased level or an impaired
utilization of these ions, such as severe hepatic insufficiency. Potassium Chloride
in Lactated Ringer's and 5% Dextrose Injection, USP should not be
administered simultaneously with blood through the same administration
set because of the likelihood of coagulation. The intravenous
administration of Potassium Chloride in Lactated Ringer's and 5%
Dextrose Injection, USP can cause fluid and/or solute overloading
resulting in dilution of serum electrolyte concentrations,
overhydration, congested states, or pulmonary edema. The risk of
dilutional states is inversely proportional to the electrolyte
concentrations of the injection. The risk of solute overload causing
congested states with peripheral and pulmonary edema is directly
proportional tothe electrolyte concentrations of the injection. In patients with
diminished renal function, administration of Potassium Chloride in
Lactated Ringer's and 5% Dextrose Injection, USP may result in sodium or
potassium retention. Potassium Chloride
in Lactated Ringer's and 5% Dextrose Injection, USP is not for use in
the treatment of lactic acidosis. In very low birth
weight infants, excessive or rapid administration of dextrose injection
may result in increased serum osmolality and possible intracerebral
hemorrhage. Potassium salts
should never be administered by IV push.
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| dailymed-drugs:104 |
BEFORE THERAPY WITH CEFAZOLIN FOR INJECTION IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEFAZOLIN. CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS. IF THIS PRODUCT IS GIVEN TO PENICILLIN-SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE CROSS-HYPERSENSITIVITY AMONG BETA-LACTAM ANTIBIOTICS HAS BEEN CLEARLY DOCUMENTED AND MAY OCCUR IN UP TO 10% OF PATIENTS WITH A HISTORY OF PENICILLIN ALLERGY. IF AN ALLERGIC REACTION TO CEFAZOLIN OCCURS, DISCONTINUE TREATMENT WITH THE DRUG. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE TREATMENT WITH EPINEPHRINE AND OTHER EMERGENCY MEASURES, INCLUDING OXYGEN, IV FLUIDS, IV ANTIHISTAMINES, CORTICOSTEROIDS, PRESSOR AMINES AND AIRWAY MANAGEMENT, AS CLINICALLY INDICATED. Pseudomembranous colitis has been reported with nearly all antibacterial agents, including cefazolin, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents. Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is a primary cause of "antibiotic-associated colitis." After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and eleotrolytes, protein supplementation and treatmentwith an oral antibacterial drug clinically effective against C. difficile colitis.
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| dailymed-drugs:105 |
The refractive stability of patients undergoing corneal refractive procedures and treated with diclofenac sodium has not been established. Patients should be monitored for a year following use in this setting. With some nonsteroidal anti-inflammatory drugs, there exists the potential for increased bleeding time due to interference with thrombocyte aggregation. There have been reports that ocularly applied nonsteroidal anti-inflammatory drugs can cause increased bleeding of ocular tissues (including hyphemas) in conjunction with ocular surgery. There is the potential for cross-sensitivity to acetylsalicylic acid, phenylacetic acid derivatives, and other nonsteroidal anti-inflammatory agents. Therefore, caution should be used when treating individuals who have previously exhibited sensitivities to these drugs.
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| dailymed-drugs:107 |
Effects in Metastatic Breast Cancer Patients:: As with other additive hormonal therapy (estrogens and androgens), hypercalcemia has been reported in some breast cancer patients with bone metastases within a few weeks of starting treatment with NOLVADEX. If hypercalcemia does occur, appropriate measures should be taken and, if severe, NOLVADEX should be discontinued.<br/>Effects on the Uterus-Endometrial Cancer and Uterine Sarcoma:: An increased incidence of uterine malignancies has been reported in association with NOLVADEX treatment. The underlying mechanism is unknown, but may be related to the estrogen-like effect of NOLVADEX. Most uterine malignancies seen in association with NOLVADEX are classified as adenocarcinoma of the endometrium. However, rare uterine sarcomas, including malignant mixed mullerian tumors (MMMT), have also been reported. Uterine sarcoma is generally associated with a higher FIGO stage (III/IV) at diagnosis, poorer prognosis, and shorter survival. Uterine sarcoma has been reported to occur more frequently among long-term users (���2 years) of NOLVADEX than non-users. Some of the uterine malignancies (endometrial carcinoma or uterine sarcoma) have been fatal. In the NSABP P-1 trial, among participants randomized to NOLVADEX there was a statistically significant increase in the incidence of endometrial cancer (33 cases of invasive endometrial cancer, compared to 14 cases among participants randomized to placebo (RR=2.48, 95% CI: 1.27-4.92). The 33 cases in participants receiving NOLVADEX were FIGO Stage I, including 20 IA, 12 IB, and 1 IC endometrial adenocarcinomas. In participants randomized to placebo, 13 were FIGO Stage I (8 IA and 5 IB) and 1 was FIGO Stage IV. Five women on NOLVADEX and 1 on placebo received postoperative radiation therapy in addition to surgery. This increasewas primarily observed among women at least 50 years of age at the time of randomization (26 cases of invasive endometrial cancer, compared to 6 cases among participants randomized to placebo (RR=4.50, 95% CI: 1.78-13.16). Among women���49 years of age at the time of randomization there were 7 cases of invasive endometrial cancer, compared to 8 cases among participants randomized to placebo (RR=0.94, 95% CI: 0.28-2.89). If age at the time of diagnosis is considered, there were 4 cases of endometrial cancer among participants���49 randomized to NOLVADEX compared to 2 among participants randomized to placebo (RR=2.21, 95% CI: 0.4-12.0). For women���50 at the time of diagnosis, there were 29 cases among participants randomized to NOLVADEX compared to 12 among women on placebo (RR=2.5, 95% CI: 1.3-4.9). The risk ratios were similar in the two groups, although fewer events occurred in younger women. Most (29 of 33 cases in the NOLVADEX group) endometrial cancers were diagnosed in symptomaticwomen, although 5 of 33 cases in the NOLVADEX group occurred in asymptomatic women. Among women receiving NOLVADEX the events appeared between 1 and 61 months (average=32 months) from the start of treatment. In an updated review of long-term data (median length of total follow-up is 6.9 years, including blinded follow-up) on 8,306 women with an intact uterus at randomization in the NSABP P-1 risk reduction trial, the incidence of both adenocarcinomas and rare uterine sarcomas was increased in women taking NOLVADEX. During blinded follow-up, there were 36 cases of FIGO Stage I endometrial adenocarcinoma (22 were FIGO Stage IA, 13 IB, and 1 IC) in women receiving NOLVADEX and 15 cases in women receiving placebo [14 were FIGO Stage I (9 IA and 5 IB), and 1 case was FIGO Stage IV]. Of the patients receiving NOLVADEX who developed endometrial cancer, one with Stage IA and 4 with Stage IB cancers received radiation therapy. In the placebo group, one patient with FIGO Stage 1B cancer received radiation therapy and the patient with FIGO Stage IVB cancer received chemotherapy and hormonal therapy. During total follow-up, endometrial adenocarcinoma was reported in 53 women randomized to NOLVADEX (30 cases of FIGO Stage IA, 20 were Stage IB, 1 was Stage IC, and 2 were Stage IIIC), and 17 women randomized to placebo (9 cases were FIGO Stage IA, 6 were Stage IB, 1 was Stage IIIC, and 1 was Stage IVB) (incidence per 1,000 women-years of 2.20 and 0.71, respectively). Some patients received post-operative radiation therapy in addition to surgery. Uterine sarcomas were reported in 4 women randomized to NOLVADEX (1 was FIGO IA, 1 was FIGO IB, 1 was FIGO IIA, and 1 was FIGO IIIC) and one patient randomized to placebo (FIGO 1A); incidence per 1,000 women-years of 0.17 and 0.04, respectively. Of the patients randomized to NOLVADEX, the FIGO IA and IB cases were a MMMT and sarcoma, respectively; the FIGO II was a MMMT; and the FIGO III was a sarcoma; and the one patient randomized to placebo had a MMMT.A similar increased incidence in endometrial adenocarcinoma and uterine sarcoma was observed among women receiving NOLVADEX in five other NSABP clinical trials. Any patient receiving or who has previously received NOLVADEX who reports abnormal vaginal bleeding should be promptly evaluated. Patients receiving or who have previously received NOLVADEX should have annual gynecological examinations and they should promptly inform their physicians if they experience any abnormal gynecological symptoms, eg, menstrual irregularities, abnormal vaginal bleeding, changes in vaginal discharge, or pelvic pain or pressure. In the P-1 trial, endometrial sampling did not alter the endometrial cancer detection rate compared to women who did not undergo endometrial sampling (0.6% with sampling, 0.5% without sampling) for women with an intact uterus. There are no data to suggest that routine endometrial sampling in asymptomatic women taking NOLVADEX to reduce the incidence of breast cancer would be beneficial.<br/>Non-Malignant Effects on the Uterus:: An increased incidence of endometrial changes including hyperplasia and polyps have been reported in association with NOLVADEX treatment. The incidence and pattern of this increase suggest that the underlying mechanism is related to the estrogenic properties of NOLVADEX. There have been a few reports of endometriosis and uterine fibroids in women receiving NOLVADEX. The underlying mechanism may be due to the partial estrogenic effect of NOLVADEX. Ovarian cysts have also been observed in a small number of premenopausal patients with advanced breast cancer who have been treated with NOLVADEX. NOLVADEX has been reported to cause menstrual irregularity or amenorrhea.<br/>Thromboembolic Effects of NOLVADEX:: There is evidence of an increased incidence of thromboembolic events, including deep vein thrombosis and pulmonary embolism, during NOLVADEX therapy. When NOLVADEX is coadminstered with chemotherapy, there may be a further increase in the incidence of thromboembolic effects. For treatment of breast cancer, the risks and benefits of NOLVADEX should be carefully considered in women with a history of thromboembolic events. In a subsmall study (N=81) of the NSABP P-1 trial, there appeared to be no benefit to screening women for Factor V Leiden and Prothrombin mutations G20210A as a means to identify those who may not be appropriate candidates for NOLVADEX therapy. Data from the NSABP P-1 trial show that participants receiving NOLVADEX without a history of pulmonary emboli (PE) had a statistically significant increase in pulmonary emboli (18-NOLVADEX, 6-placebo, RR=3.01, 95% CI: 1.15- 9.27). Three of the pulmonary emboli, all in the NOLVADEX arm, were fatal. Eighty-seven percent of the cases of pulmonary embolism occurred in women at least 50 years of age at randomization. Among women receiving NOLVADEX, the events appeared between 2 and 60 months (average=27 months) from the start of treatment. In this same population, a non-statistically significant increase in deep vein thrombosis (DVT) was seen in the NOLVADEX group (30-NOLVADEX, 19-placebo; RR=1.59, 95% CI: 0.86-2.98). The same increase in relative risk was seen in women���49 and in women���50, although fewer events occurred in younger women. Women with thromboembolic events were at risk for a second related event (7 out of 25 women on placebo, 5 out of 48 women on NOLVADEX) and were at risk for complications of the event and its treatment (0/25 on placebo, 4/48 on NOLVADEX). Among women receiving NOLVADEX, deep vein thrombosis events occurred between 2 and 57 months (average=19 months) from the start of treatment. There was a non-statistically significant increase in stroke among patients randomized to NOLVADEX (24-Placebo; 34-NOLVADEX; RR=1.42; 95% CI 0.82-2.51). Six of the 24 strokes in the placebo group were considered hemorrhagic in origin and 10 of the 34 strokes in the NOLVADEX group were categorized as hemorrhagic. Seventeen ofthe 34 strokes in the NOLVADEX group were considered occlusive and 7 were considered to be of unknown etiology. Fourteen of the 24 strokes on the placebo arm were reported to be occlusive and 4 of unknown etiology. Among these strokes 3 strokes in the placebo group and 4 strokes in the NOLVADEX group were fatal. Eighty-eight percent of the strokes occurred in women at least 50 years of age at the time of randomization. Among women receiving NOLVADEX, the events occurred between 1 and 63 months (average=30 months) from the start of treatment.<br/>Effects on the liver: Liver cancer:: In the Swedish trial using adjuvant NOLVADEX 40 mg/day for 2-5 years, 3 cases of liver cancer have been reported in the NOLVADEX-treated group vs. 1 case in the observation group . In other clinical trials evaluating NOLVADEX, no cases of liver cancer have been reported to date. One case of liver cancer was reported in NSABP P-1 in a participant randomized to NOLVADEX.<br/>Effects on the liver: Non-malignant effects:: NOLVADEX has been associated with changes in liver enzyme levels, and on rare occasions, a spectrum of more severe liver abnormalities including fatty liver, cholestasis, hepatitis and hepatic necrosis. A few of these serious cases included fatalities. In most reported cases the relationship to NOLVADEX is uncertain. However, some positive rechallenges and dechallenges have been reported. In the NSABP P-1 trial, few grade 3-4 changes in liver function (SGOT, SGPT, bilirubin, alkaline phosphatase) were observed (10 on placebo and 6 on NOLVADEX). Serum lipids were not systematically collected.<br/>Other cancers:: A number of second primary tumors, occurring at sites other than the endometrium, have been reported following the treatment of breast cancer with NOLVADEX in clinical trials. Data from the NSABP B-14 and P-1 studies show no increase in other (non-uterine) cancers among patients receiving NOLVADEX. Whether an increased risk for other (non-uterine) cancers is associated with NOLVADEX is still uncertain and continues to be evaluated.<br/>Effects on the Eye:: Ocular disturbances, including corneal changes, decrement in color vision perception, retinal vein thrombosis, and retinopathy have been reported in patients receiving NOLVADEX. An increased incidence of cataracts and the need for cataract surgery have been reported in patients receiving NOLVADEX. In the NSABP P-1 trial, an increased risk of borderline significance of developing cataracts among those women without cataracts at baseline (540-NOLVADEX; 483-placebo; RR=1.13, 95% CI: 1.00-1.28) was observed. Among these same women, NOLVADEX was associated with an increased risk of having cataract surgery (101-NOLVADEX; 63-placebo; RR=1.62, 95% CI 1.18-2.22) . Among all women on the trial (with or without cataracts at baseline), NOLVADEX was associated with an increased risk of having cataract surgery (201-NOLVADEX; 129-placebo; RR=1.58, 95% CI 1.26-1.97). Eye examinations were not required during the study. No other conclusions regarding non-cataract ophthalmic events can be made.<br/>Pregnancy Category D:: NOLVADEX may cause fetal harm when administered to a pregnant woman. Women should be advised not to become pregnant while taking NOLVADEX or within 2 months of discontinuing NOLVADEX and should use barrier or nonhormonal contraceptive measures if sexually active. Tamoxifen does not cause infertility, even in the presence of menstrual irregularity. Effects on reproductive functions are expected from the antiestrogenic properties of the drug. In reproductive studies in rats at dose levels equal to or below the human dose, nonteratogenic developmental skeletal changes were seen and were found reversible. In addition, in fertility studies in rats and in teratology studies in rabbits using doses at or below those used in humans, a lower incidence of embryo implantation and a higher incidence offetal death or retarded in utero growth were observed, with slower learning behavior in some rat pups when compared to historical controls. Several pregnant marmosets were dosed with 10 mg/kg/day (about 2-fold the daily maximum recommended human dose on a mg/mbasis) during organogenesis or in the last half of pregnancy. No deformations were seen and, although the dose was high enough to terminate pregnancy in some animals, those that did maintain pregnancy showed no evidence of teratogenic malformations. In rodent models of fetal reproductive tract development, tamoxifen (at doses 0.002 to 2.4-fold the daily maximum recommended human dose on a mg/mbasis) caused changes in both sexes that are similar to those caused by estradiol, ethynylestradiol and diethylstilbestrol. Although the clinical relevance of these changes is unknown, some of these changes, especially vaginal adenosis, are similar to those seen in young women who were exposed to diethylstilbestrolin utero and who have a 1 in 1000 risk of developing clear-cell adenocarcinoma of the vagina or cervix. To date, in utero exposure to tamoxifen has not been shown to cause vaginal adenosis, or clear-cell adenocarcinoma of the vagina or cervix, in young women. However, only a small number of young women have been exposed to tamoxifen in utero, and a smaller number have been followed long enough (to age 15-20) to determine whether vaginal or cervical neoplasia could occur as a result of this exposure. There are no adequate and well-controlled trials of tamoxifen in pregnant women. There have been a small number of reports of vaginal bleeding, spontaneous abortions, birth defects, and fetal deaths in pregnant women. If this drug is used during pregnancy, or the patient becomes pregnant while taking this drug, or within approximately two months after discontinuing therapy, the patient should be apprised of the potential risks to the fetus including the potential long-termrisk of a DES-like syndrome.<br/>Reduction in Breast Cancer Incidence in High Risk Women - Pregnancy Category D:: For sexually active women of child-bearing potential, NOLVADEX therapy should be initiated during menstruation. In women with menstrual irregularity, a negative B-HCG immediately prior to the initiation of therapy is sufficient .
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Cessation of Therapy with
COREG CR: Patients with coronary artery disease, who are being
treated with COREG CR, should be advised against abrupt discontinuation
of therapy. Severe exacerbation of angina and the occurrence of myocardial
infarction and ventricular arrhythmias have been reported in angina
patients following the abrupt discontinuation of therapy with��-blockers.
The last 2 complications may occur with or without preceding exacerbation
of the angina pectoris. As with other��-blockers, when discontinuation
of COREG CR is planned, the patients should be carefully observed
and advised to limit physical activity to a minimum. COREG CR
should be discontinued over 1 to 2 weeks whenever possible. If the
angina worsens or acute coronary insufficiency develops, it is recommended
that COREG CR be promptly reinstituted, at least temporarily.
Because coronary artery disease is common and may be unrecognized,
it may be prudent not to discontinue COREG CR therapy abruptly
even in patients treated only for hypertension or heart failure (see
DOSAGE AND ADMINISTRATION).<br/>Peripheral Vascular Disease: ��-blockers can precipitate or aggravate symptoms
of arterial insufficiency in patients with peripheral vascular disease.
Caution should be exercised in such individuals.<br/>Anesthesia and Major Surgery: If treatment with COREG CR is to be continued
perioperatively, particular care should be taken when anesthetic agents
which depress myocardial function, such as ether, cyclopropane, and
trichloroethylene, are used. See OVERDOSAGE for information on treatment
of bradycardia and hypertension.<br/>Diabetes and Hypoglycemia: In general,��-blockers may mask some of the
manifestations of hypoglycemia, particularly tachycardia. Nonselective��-blockers may potentiate insulin-induced hypoglycemia and delay
recovery of serum glucose levels. Patients subject to spontaneous
hypoglycemia, or diabetic patients receiving insulin or oral hypoglycemic
agents, should be cautioned about these possibilities. In heart failure
patients, there is a risk of worsening hyperglycemia (see PRECAUTIONS,
Effects on Glycemic Control in Type 2 Diabetic Patients).<br/>Thyrotoxicosis: ��-adrenergic blockade may mask clinical signs
of hyperthyroidism, such as tachycardia. Abrupt withdrawal of��-blockade
may be followed by an exacerbation of the symptoms of hyperthyroidism
or may precipitate thyroid storm.
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| dailymed-drugs:109 |
Cigarette smoking increases the risk of serious cardiovascular side effects from oral contraceptive use. This risk increases with age and with heavy smoking (15 or more cigarettes per day) and is quite marked in women over 35 years of age. Women who use oral contraceptives should be strongly advised not to smoke. YAZ contains 3 mg of the progestin drospirenone that has antimineralocorticoid activity, including the potential for hyperkalemia in high-risk patients, comparable to a 25 mg dose of spironolactone. YAZ should not be used in patients with conditions that predispose to hyperkalemia (i.e. renal insufficiency, hepatic dysfunction and adrenal insufficiency). Women receiving daily, long-term treatment for chronic conditions or diseases with medications that may increase serum potassium should have their serum potassium level checked during the first treatment cycle. Medications that may increase serum potassium include ACE inhibitors, angiotensin���II receptor antagonists, potassium-sparing diuretics, potassium supplementation, heparin, aldosterone antagonists, and NSAIDS. The use of oral contraceptives is associated with increased risks of several serious conditions including venous and arterial thrombotic and thromboembolic events (such as myocardial infarction, thromboembolism, stroke), hepatic neoplasia, gallbladder disease, and hypertension. The risk of serious morbidity or mortality is very small in healthy women without underlying risk factors. The risk of morbidity and mortality increases significantly in the presence of other underlying risk factors such ashypertension, hyperlipidemias, obesity and diabetes. Practitioners prescribing oral contraceptives should be familiar with the following information relating to these risks. The information contained in this package insert is based principally on studies carried out in patients who used oral contraceptives with higher formulations of estrogens and progestogens than those in common use today. The effect of long���term use of the oral contraceptives with lower formulations of both estrogens and progestogens remains to be determined. Throughout this labeling, epidemiologic studies reported are of two types: retrospective or case control studies and prospective or cohort studies. Case control studies provide a measure of the relative risk of a disease, namely, a ratio of the incidence of a disease among oral contraceptive users to that among nonusers. The relative risk does not provide information on the actual clinical occurrence of a disease. Cohort studies provide a measure of attributable risk, which is the difference in the incidence of disease between oral contraceptive users and nonusers. The attributable risk does provide information about the actual occurrence of a disease in the population. For further information, the reader is referred to a text on epidemiologic methods.<br/>1. THROMBOEMBOLIC DISORDERS AND OTHER VASCULAR PROBLEMS:<br/>a. Myocardial infarction: An increased risk of myocardial infarction has been attributed to oral contraceptive use. This risk is primarily in smokers or women with other underlying risk factors for coronary���artery disease such as hypertension, hypercholesterolemia, morbid obesity, and diabetes. The relative risk of heart attack for current oral contraceptive users has been estimated to be two to six. The risk is very low under the age of 30. Smoking in combination with oral contraceptive use has been shown to contribute substantially to the incidence of myocardial infarctions in women in their mid���thirties or older with smoking accounting for the majority of excess cases. Mortality rates associated with circulatory disease have been shown to increase substantially in smokers over the age of 35 and nonsmokers over the age of 40 (Table III) among women who use oral contraceptives. Oral contraceptives may compound the effects of well���known risk factors, such as hypertension, diabetes, hyperlipidemias, age and obesity. In particular, some progestogens are known to decrease HDL cholesterol and cause glucose intolerance, while estrogens may create a state of hyperinsulinism. Oral contraceptives have been shown to increase blood pressure among users . Similar effects on risk factors have been associated with an increased risk of heart disease. Oral contraceptives must be used with caution in women with cardiovascular disease risk factors.<br/>b. Thromboembolism: An increased risk of thromboembolic and thrombotic disease associated with the use of oral contraceptives is well established. Case control studies have found the relative risk of users compared to nonusers to be 3 for the first episode of superficial venous thrombosis, 4 to 11 for deep vein thrombosis or pulmonary embolism, and 1.5 to 6 for women with predisposing conditions for venous thromboembolic disease. Cohort studies have shown the relative risk to be somewhat lower, about 3 for new cases and about 4.5 for new cases requiring hospitalization. The risk of thromboembolic disease due to oral contraceptives is not related to length of use and disappears after pill use is stopped. A two- to four-fold increase in the relative risk of post-operative thromboembolic complications has been reported with the use of oral contraceptives. The relative risk of venous thrombosis in women who have predisposing conditions is twice that of women without such medical conditions. If feasible, oral contraceptives should be discontinued from at least four weeks prior to and for two weeks after elective surgery of a type associated with an increase in risk of thromboembolism andduring and following prolonged immobilization. Since the immediate postpartum period is also associated with an increased risk of thromboembolism, combined oral contraceptives should be started no earlier than four to six weeks after delivery and at that time only in women who elect not to breast feed.<br/>c. Cerebrovascular diseases: Oral contraceptives have been shown to increase both the relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes), although, in general, the risk is greatest among older (>35 years), hypertensive women who also smoke. Hypertension was found to be a risk factor, for both users and nonusers, for both types of strokes, while smoking interacted to increase the risk for hemorrhagic strokes. In a large study, the relative risk of thrombotic strokes has been shown to range from 3 for normotensive users to 14 for users with severe hypertension. The relative risk of hemorrhagic stroke is reported to be 1.2 for nonsmokers who used oral contraceptives, 2.6 for smokers who did not use oral contraceptives, 7.6 for smokers who used oral contraceptives, 1.8 for normotensive users and 25.7 for users with severe hypertension. The attributable risk is also greater in older women. Oral contraceptives also increase the risk for stroke in women with other underlying risk factors such as certain inherited or acquired thrombophilias, hyperlipidemias, and obesity. Women with migraine (particularly migraine with aura) who take combination oral contraceptives may be at an increased risk of stroke.<br/>d. Dose-related risk of vascular disease from oral contraceptives: A positive association has been observed between the amount of estrogen and progestogen in oral contraceptives and the risk of vascular disease. A decline in serum high-density lipoproteins (HDL) has been reported with many progestational agents. A decline in serum high-density lipoproteins has been associated with an increased incidence of ischemic heart disease. Because estrogens increase HDL cholesterol, the net effect of an oral contraceptive depends on a balance achieved between doses of estrogen and progestogen and the nature and absolute amount of progestogen used in the contraceptive. The amount of both hormones should be considered in the choice of an oral contraceptive. Minimizing exposure to estrogen and progestogen is in keeping with good principles of therapeutics. For any particular estrogen/progestogen combination, the dosage regimen prescribed should be one which contains the least amount of estrogen and progestogen that is compatible with a low failure rate and the needs of the individual patient. New acceptors of oral contraceptive agents should be started on preparations containing the lowest estrogen content that is judged appropriate for the individual patient.<br/>e. Persistence of risk of vascular disease: There are two studies which have shown persistence of risk of vascular disease for ever-users of oral contraceptives. In a study in the United States, the risk of developing myocardial infarction after discontinuing oral contraceptives persists for at least 9 years for women aged 40 to 49 years who had used oral contraceptives for five or more years, but this increased risk was not demonstrated in other age groups. In another study in Great Britain, the risk of developing cerebrovascular disease persisted for at least 6 years after discontinuation of oral contraceptives, although excess risk was very small. However, both studies were performed with oral contraceptive formulations containing 50 micrograms or higher of estrogens.<br/>2. ESTIMATES OF MORTALITY FROM CONTRACEPTIVE USE: One study gathered data from a variety of sources which have estimated the mortality rate associated with different methods of contraception at different ages (Table IV). These estimates include the combined risk of death associated with contraceptive methods plus the risk attributable to pregnancy in the event of method failure. Each method of contraception has its specific benefits and risks. The study concluded that with the exception of oral contraceptive users 35 and older who smoke and 40 and older who do not smoke, mortality associatedwith all methods of birth control is below that associated with childbirth. The observation of a possible increase in risk of mortality with age for oral contraceptive users is based on data gathered in the 1970's���but not reported until 1983. However, current clinical practice involves the use of lower estrogen dose formulations combined with careful restriction of oral contraceptive use to women who do not have the various risk factors listed in this labeling. Because of these changes in practice and, also, because of some limited new data which suggest that the risk of cardiovascular disease with the use of oral contraceptives may now be less than previously observed, the Fertility and Maternal Health Drugs Advisory Committee was asked to review the topic in 1989. The Committee concluded that although cardiovascular disease risks may be increased with oral contraceptive use after age 40 in healthy nonsmoking women (even with the newer low���dose formulations), there are greater potential health risks associated with pregnancy in older women and with the alternative surgical and medical procedures which may be necessary if such women do not have access to effective and acceptable means of contraception. Therefore, the Committee recommended that the benefits of oral contraceptive use by healthy nonsmoking women over 40 may outweigh the possible risks. Of course, women of all ages who take oral contraceptives, should take the lowest possible dose formulation that is effective.<br/>3. CARCINOMA OF THE REPRODUCTIVE ORGANS AND BREASTS: Numerous epidemiological studies have been performed on the incidence of breast, endometrial, ovarian and cervical cancer in women using oral contraceptives. Although the risk of having breast cancer diagnosed may be slightly increased among current and recent users of combined oral contraceptives (RR=1.24), this excess risk decreases over time after combination oral contraceptive discontinuation and by 10 years after cessation the increased risk disappears. The risk does not increase with duration of use and no consistent relationships have been found with dose or type of steroid. The patterns of risk are also similar regardless of a woman's reproductive history or her family breast cancer history. The subgroup for whom risk has been found to be significantly elevated is women who first used oral contraceptives before age 20, but because breast cancer is so rare at these young ages, the number of cases attributable to this early oral contraceptive use is extremely small. Breast cancers diagnosed in current or previous OC users tend to be less clinically advanced than in never users. Women who currently have or have had breast cancer should not use oral contraceptives because breast cancer is a hormonally-sensitive tumor. Some studies suggest that oral contraceptive use has been associated with an increase in the risk of cervical intraepithelial neoplasia in some populations of women. However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behavior and other factors. In spite of many studies of the relationship between oral contraceptive use and breast and cervical cancers, a cause-and-effect relationship has not been established.<br/>4. HEPATIC NEOPLASIA: Benign hepatic adenomas are associated with oral contraceptive use, although the incidence of benign tumors is rare in the United States. Indirect calculations have estimated the attributable risk to be in the range of 3.3 cases/100,000 for users, a risk that increases after four or more years of use. Rupture of rare, benign, hepatic adenomas may cause death through intra-abdominal hemorrhage. Studies from Britain have shown an increased risk of developing hepatocellular carcinoma in long-term (>8 years) oral contraceptive users. However, these cancers are extremely rare in the U.S. and the attributable risk (the excess incidence) of liver cancers in oral contraceptive users approaches less than one per million users.<br/>5. OCULAR LESIONS: There have been clinical case reports of retinal thrombosis associated with the use of oral contraceptives, which may lead to partial or complete loss of vision. Oral contraceptives should be discontinued if there is unexplained partial or complete loss of vision; onset of proptosis or diplopia; papilledema; or retinal vascular lesions. Appropriate diagnostic and therapeutic measures should be undertaken immediately.<br/>6. ORAL CONTRACEPTIVE USE BEFORE OR DURING EARLY PREGNANCY: Extensive epidemiological studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy. Studies also do not suggest a teratogenic effect, particularly in so far as cardiac anomalies and limb-reduction defects are concerned, when taken inadvertently during early pregnancy. The administration of oral contraceptives to induce withdrawal bleeding should not be used as a test for pregnancy. Oral contraceptives should not be used during pregnancy to treat threatened or habitual abortion. It is recommended that for any patient who has missed two consecutive periods, pregnancy should be ruled out. If the patient has not adhered to the prescribed dosing schedule, the possibility of pregnancy should be considered at the time of the first missed period. Oral contraceptive use should be discontinued if pregnancy is confirmed.<br/>7. GALLBLADDER DISEASE: Earlier studies have reported an increased lifetime relative risk of gallbladder surgery in users of oral contraceptives and estrogens. More recent studies, however, have shown that the relative risk of developing gallbladder disease among oral contraceptive users may be minimal. The recent findings of minimal risk may be related to the use of oral contraceptive formulations containing lower hormonal doses of estrogens and progestogens.<br/>8. CARBOHYDRATE AND LIPID METABOLIC EFFECTS: Oral contraceptives have been shown to cause glucose intolerance in a significant percentage of users. Oral contraceptives containing greater than 75 micrograms of estrogens cause hyperinsulinism, while lower doses of estrogen cause less glucose intolerance. Progestogens increase insulin secretion and create insulin resistance, this effectvarying with different progestational agents. However, in the nondiabetic woman, oral contraceptives appear to have no effect on fasting blood glucose. Because of these demonstrated effects, prediabetic and diabetic women should be carefully observed while taking oral contraceptives. A small proportion of women will have persistent hypertriglyceridemia while on the pill. As discussed earlier (see WARNINGSMyocardial infarction andDose-related risk of vascular disease from oral contraceptives ), changes in serum triglycerides and lipoprotein levels have been reported in oral contraceptive users.<br/>9. ELEVATED BLOOD PRESSURE: Women with severe hypertension should not be started on hormonal contraceptives . An increase in blood pressure has been reported in women taking oral contraceptives and this increase is more likely in older oral contraceptive users and with continued use. Data from the Royal College of General Practitioners and subsequent randomized trials have shown that the incidence of hypertension increases with increasing concentrations of progestogens. Women with a history of hypertension or hypertension-related diseases, or renal disease should be encouraged to use another method of contraception. If women with hypertension elect to use oral contraceptives, they should be monitored closely, and if significant elevation of blood pressure occurs, oral contraceptives should be discontinued. For most women, elevated blood pressure will return to normal after stopping oral contraceptives and there is no difference in the occurrence of hypertension among ever- and never-users.<br/>10. HEADACHE: The onset or exacerbation of migraine or development of headache with a new pattern which is recurrent, persistent or severe requires discontinuation of oral contraceptives and evaluation of the cause.<br/>11. BLEEDING IRREGULARITIES: Breakthrough bleeding and spotting are sometimes encountered in patients on oral contraceptives, especially during the first three months of use. Nonhormonal causes should be considered and adequate diagnostic measures taken to rule out malignancy or pregnancy in the event of breakthrough bleeding, as in the case of any abnormal vaginal bleeding. If pathology has been excluded, time or a change to another formulation may solve the problem. In the event of amenorrhea, pregnancy should be ruled out. Some women may encounter post-pill amenorrhea or oligomenorrhea, especially when such a condition was pre-existent.
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| dailymed-drugs:110 |
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination with antiretrovirals. Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy, including TYZEKA(telbivudine). Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy. If appropriate, resumption of anti-hepatitis B therapy may be warranted.
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| dailymed-drugs:111 |
Cardiovascular Disease:: Cevimeline can potentially alter cardiac conduction and/or heart rate. Patients with significant cardiovascular disease may potentially be unable to compensate for transient changes in hemodynamics or rhythm induced by EVOXAC'. EVOXAC' should be used with caution and under close medical supervision in patients with a history of cardiovascular disease evidenced by angina pectoris or myocardial infarction.<br/>Pulmonary Disease:: Cevimeline can potentially increase airway resistance, bronchial smooth muscle tone, and bronchial secretions. Cevimeline should be administered with caution and with close medical supervision to patients with controlled asthma, chronic bronchitis, or chronic obstructive pulmonary disease.<br/>Ocular:: Ophthalmic formulations of muscarinic agonists have been reported to cause visual blurring which may result in decreased visual acuity, especially at night and in patients with central lens changes, and to cause impairment of depth perception. Caution should be advised while driving at night or performing hazardous activities in reduced lighting.
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| dailymed-drugs:112 |
NOT FOR INJECTION. IQUIX solution should not be injected subconjunctivally, nor should it be introduced directly into the anterior chamber of the eye. In patients receiving systemic quinolones, serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported, some following the first dose. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema (including laryngeal, pharyngeal or facial edema), airway obstruction, dyspnea, urticaria, and itching. If an allergic reaction to levofloxacin occurs, discontinue the drug. Serious acute hypersensitivity reactions may require immediate emergency treatment. Oxygen and airway management should be administered as clinically indicated.
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| dailymed-drugs:113 |
Cardiovascular Effects::<br/>Cardiovascular Thrombotic Events:: Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the signs and/or symptoms of serious CV events and the steps to take if they occur. There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID does increase the risk of serious GI events (see WARNINGS , Gastrointestinal (GI) Effects - Risk of GI Ulceration , Bleeding , and Perforation). Two large, controlled, clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke .<br/>Hypertension:: NSAIDs, including meloxicam, can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including meloxicam, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout thecourse of therapy.<br/>Congestive Heart Failure and Edema:: Fluid retention and edema have been observed in some patients taking NSAIDs. Meloxicam should be used with caution in patients with fluid retention, hypertension, or heart failure.<br/>Gastrointestinal (GI) Effects - Risk of GI Ulceration, Bleeding, and Perforation:: NSAIDs, including meloxicam, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients, who develop a serious upper GI adverse event on NSAID therapy, is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs, occur in approximately 1% of patients treated for 3-6 months, and in about 2-4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk. NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding who use NSAIDs have a greater than 10-fold increased risk for developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore, special care should be taken in treating this population. To minimize the potential risk for an adverse GI event in patients treated with an NSAID, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high-risk patients, alternate therapies that do not involve NSAIDs should be considered.<br/>Renal Effects:: Long-term administration of NSAIDs, including meloxicam, can result in renal papillary necrosis, renal insufficiency, acute renal failure, and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a nonsteroidal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and angiotensin II receptor antagonists, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.<br/>Advanced Renal Disease:: No information is available from controlled clinical studies regarding the use of meloxicam in patients with advanced renal disease. Therefore, treatment with meloxicam is not recommended in these patients with advanced renal disease. If meloxicam therapy must be initiated, close monitoring of the patient's renal function is advisable.<br/>Anaphylactoid Reactions:: As with other NSAIDS, anaphylactoid reactions have occurred in patients without known prior exposure to meloxicam. Meloxicam should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs . Emergency help should be sought in cases where an anaphylactoid reaction occurs.<br/>Skin Reactions:: NSAIDs, including meloxicam, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Patients should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.<br/>Pregnancy:: In late pregnancy, as with other NSAIDs, meloxicam should be avoided because it may cause premature closure of the ductus arteriosus.
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| dailymed-drugs:114 |
Contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.
|
| dailymed-drugs:1023 |
Contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.
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| dailymed-drugs:1904 |
Contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.
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| dailymed-drugs:115 |
Dihydroergotamine mesylate injection should only be used where a clear diagnosis of migraine headache has been established.<br/>CYP 3A4 Inhibitors: (e.g. Macrolide Antibiotics and Protease Inhibitors) There have been rare reports of serious adverse events in connection with the coadministration of dihydroergotamine and potent CYP 3A4 inhibitors, such as protease inhibitors and macrolide antibiotics, resulting in vasospasm that led to cerebral ischemia and/or ischemia of the extremities. The use of potent CYP 3A4 inhibitors with dihydroergotamine should therefore be avoided Examples of some of the more potent CYP 3A4 inhibitors include: anti-fungals ketoconazole and itraconazole, the protease inhibitors ritonavir, nelfinavir, and indinavir, and macrolide antibiotics erythromycin, clarithromycin, and troleandomycin. Other less potent CYP 3A4 inhibitors should be administered with caution. Less potent inhibitors include saquinavir, nefazodone, fluconazole, grapefruit juice, fluoxetine, fluvoxamine, zileuton, and clotrimazole. These lists are not exhaustive, and the prescriber should consider the effects on CYP 3A4 of other agents being considered for concomitant use with dihydroergotamine.<br/>Fibrotic Complications: There have been reports of pleural and retroperitoneal fibrosis in patients following prolonged daily use of injectable dihydroergotamine mesylate. Rarely, prolonged daily use of other ergot alkaloid drugs has been associated with cardiac valvular fibrosis. Rare cases have also been reported in association with the use of injectable dihydroergotamine mesylate; however, in those cases, patients also received drugs known to be associated with cardiac valvular fibrosis. Administration of dihydroergotamine mesylate injection should not exceed the dosing guidelines and should not be used for chronic daily administration<br/>Risk of Myocardial Ischemia and/or Infarction and Other Adverse Cardiac Events: Dihydroergotamine mesylate injection should not be used by patients with documented ischemic or vasospastic coronary artery disease. It is strongly recommended that dihydroergotamine mesylate injection not be given to patients in whom unrecognized coronary artery disease (CAD) is predicted by the presence of risk factors (e.g., hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, females who are surgically or physiologically postmenopausal, or males who are over 40 years of age) unless a cardiovascular evaluation provides satisfactory clinical evidence that the patient is reasonably free of coronary artery and ischemic myocardial disease or other significant underlying cardiovascular disease. The sensitivity of cardiac diagnostic procedures to detect cardiovascular disease or predisposition to coronary artery vasospasm is modest, at best. If, during the cardiovascular evaluation, the patient's medical history or electrocardiographic investigations reveal findings indicative of or consistent with coronary artery vasospasm or myocardial ischemia, dihydroergotamine mesylate injection should not be administered. For patients with risk factors predictive of CAD who are determined to have a satisfactory cardiovascular evaluation, it is strongly recommended that administration of the first dose of dihydroergotamine mesylate injection take place in the setting of a physician's office or similar medically staffed and equipped facility unless the patient has previously received dihydroergotamine mesylate. Because cardiac ischemia can occur in the absence of clinical symptoms, consideration should begiven to obtaining on the first occasion of use an electrocardiogram (ECG) during the interval immediately following dihydroergotamine mesylate injection, in those patients with risk factors. It is recommended that patients who are intermittent long-term users of dihydroergotamine mesylate injection and who have or acquire risk factors predictive of CAD, as described above, undergo periodic interval cardiovascular evaluation as they continue to use dihydroergotamine mesylate injection. The systematic approach described above is currently recommended as a method to identify patients in whom dihydroergotamine mesylate injection may be used to treat migraine headaches with an acceptable margin of cardiovascular safety.<br/>Cardiac Events and Fatalities: The potential for adverse cardiac events exists. Serious adverse cardiac events, including acute myocardial infarction, life-threatening disturbances of cardiac rhythm, and death have been reported to have occurred following the administration of dihydroergotamine mesylate injection. Considering the extent of use of dihydroergotamine mesylate in patients with migraine, the incidence of these events is extremely low.<br/>Drug-Associated Cerebrovascular Events and Fatalities: Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported in patients treated with dihydroergotamine mesylate injection; and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the dihydroergotamine mesylate injection having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine, when they were not. It should be noted that patients with migraine may be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, transient ischemic attack).<br/>Other Vasospasm Related Events: Dihydroergotamine mesylate injection, like other ergot alkaloids, may cause vasospastic reactions other than coronary artery vasospasm. Myocardial, peripheral vascular, and colonic ischemia have been reported with dihydroergotamine mesylate injection. Dihydroergotamine mesylate injection associated vasospastic phenomena may also cause muscle pains, numbness, coldness, pallor, and cyanosis of the digits. In patients with compromised circulation, persistent vasospasm may result in gangrene or death. Dihydroergotamine mesylate injection should be discontinued immediately if signs or symptoms of vasoconstriction develop.<br/>Increase in Blood Pressure: Significant elevation in blood pressure has been reported on rare occasions in patients with and without a history of hypertension treated with dihydroergotamine mesylate injection. Dihydroergotamine mesylate injection is contraindicated in patients with uncontrolled hypertension. An 18% increase in mean pulmonary artery pressure was seen following dosing with another 5-HTagonist in a study evaluating subjects undergoing cardiac catheterization.
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| dailymed-drugs:118 |
Cardiovascular Effects:<br/>Cardiovascular Thrombotic Events: Clinical trials of several COX-2 selective and nonselective
NSAIDs of up to three years duration have shown an increased
risk of serious cardiovascular (CV) thrombotic events, myocardial
infarction, and stroke, which can be fatal. All NSAIDs, both COX-2
selective and nonselective, may have a similar risk. Patients with
known CV disease or risk factors for CV disease may be at greater
risk. To minimize the potential risk for an adverse CV event in patients
treated with an NSAID, the lowest effective dose should be used for
the shortest duration possible. Physicians and patients should remain
alert for the development of such events, even in the absence of previous
CV symptoms. Patients should be informed about the signs and/or symptoms
of serious CV events and the steps to take if they occur. There is no consistent evidence that concurrent use of
aspirin mitigates the increased risk of serious CV thrombotic events
associated with NSAID use. The concurrent use of aspirin and an NSAID
does increase the risk of serious GI events . Two large, controlled, clinical trials of
a COX-2 selective NSAID for the treatment of pain in the first 10-14
days following CABG surgery found an increased incidence of myocardial
infarction and stroke .<br/>Hypertension: NSAIDs, including INDOCIN, can lead to onset of new
hypertension or worsening of pre-existing hypertension, either of
which may contribute to the increased incidence of CV events. Patients
taking thiazides or loop diuretics may have impaired response to these
therapies when taking NSAIDs. NSAIDs, including INDOCIN, should be
used with caution in patients with hypertension. Blood pressure (BP)
should be monitored closely during the initiation of NSAID treatment
and throughout the course of therapy.<br/>Congestive Heart Failure and Edema: Fluid retention and edema have been observed in some
patients taking NSAIDs. INDOCIN should be used with caution in patientswith fluid retention or heart failure. In a
study of patients with severe heart failure and hyponatremia, INDOCIN
was associated with significant deterioration of circulatory hemodynamics,
presumably due to inhibition of prostaglandin dependent compensatory
mechanisms.<br/>Gastrointestinal Effects:<br/>Risk of Ulceration, Bleeding, and Perforation: NSAIDs, including INDOCIN, can cause serious gastrointestinal
(GI) adverse events including inflammation, bleeding, ulceration,
and perforation of the esophagus, stomach, small intestine, or large
intestine, which can be fatal. These serious adverse events can occur
at any time, with or without warning symptoms, in patients treated
with NSAIDs. Only one in five patients, who develop a serious upper
GI adverse event on NSAID therapy is symptomatic. Upper GI ulcers,
gross bleeding, or perforation caused by NSAIDs occur in approximately
1% of patients treated for 3-6 months, and in about 2-4% of patients
treated for one year. These trends continue with longer duration
of use, increasing the likelihood of developing a serious GI event
at some time during the course of therapy. However, even short-term
therapy is not without risk. Rarely, in patients
taking INDOCIN, intestinal ulceration has been associated with stenosis
and obstruction. Gastrointestinal bleeding without obvious ulcer formation
and perforation of pre-existing sigmoid lesions (diverticulum, carcinoma,
etc.) have occurred. Increased abdominal pain in ulcerative colitis
patients or the development of ulcerative colitis and regional ileitis
have been reported to occur rarely. NSAIDs should
be prescribed with extreme caution in those with prior history of
ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease and/or gastrointestinal
bleeding who use NSAIDs have a greater than 10���fold
increased risk for developing a GI bleed compared to patients with
neither of these risk factors. Other factors that increase the risk
for GI bleeding in patients treated with NSAIDs include concomitant
use of oral corticosteroids or anticoagulants, longer duration of
NSAID therapy, smoking, use of alcohol, older age, and poor general
health status. Most spontaneous reports of fatal GI events are in
elderly or debilitated patients and therefore, special care should
be taken in treating this population. To minimize
the potential risk for an adverse GI event in patients treated with
an NSAID, the lowest effective dose should be used for the shortest
possible duration. Patients and physicians should remain alert for
signs and symptoms of GI ulceration and bleeding during NSAID therapy
and promptly initiate additional evaluation and treatment if a serious
GI adverse event is suspected. This should include discontinuation
of the NSAID until a serious GI adverse event is ruled out. For high
risk patients, alternate therapies that do not involve NSAIDs should
be considered.<br/>Renal Effects: Long-term administration of NSAIDs has resulted in
renal papillary necrosis and other renal injury. Renal toxicity has
also been seen in patients in whom renal prostaglandins have a compensatory
role in the maintenance of renal perfusion. In these patients, administration
of a nonsteroidal anti-inflammatory drug may cause a dose-dependent
reduction in prostaglandin formation and, secondarily, in renal blood
flow, which may precipitate over renal decompensation. Patients at
greatest risk of this reaction are those with impaired renal function,
heart failure, liver dysfunction, those taking diuretics and ACE inhibitors,
patients with volume depletion, and the elderly. Discontinuation of
NSAID therapy is usually followed by recovery to the pretreatment
state. Increases in serum potassium concentration,
including hyperkalemia, have been reported with use of INDOCIN, even
in some patients without renal impairment. In patients with normal
renal function, these effects have been attributed to a hyporeninemic-hypoaldosteronism
state .<br/>Advanced Renal Disease: No information is available from controlled clinical
studies regarding the use of INDOCIN in patients with advanced renal
disease. Therefore, treatment with INDOCIN is not recommended in these
patients with advanced renal disease. If INDOCIN therapy must be initiated,
close monitoring of the patient's renal function is advisable.<br/>Anaphylactic/Anaphylactoid Reactions: As with other NSAIDs, anaphylactic/anaphylactoid
reactions may occur in patients without known prior exposure to INDOCIN.
INDOCIN should not be given to patients with the aspirin triad. This
symptom complex typically occurs in asthmatic patients who experience
rhinitis with or without nasal polyps, or who exhibit severe, potentially
fatal bronchospasm after taking aspirin or other NSAIDs . Emergency help should be sought in cases where an anaphylactic/anaphylactoid reaction occurs.<br/>Skin Reactions: NSAIDs, including INDOCIN, can cause serious skin
adverse events such as exfoliative dermatitis, Stevens���Johnson
Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be
fatal. These serious events may occur without warning. Patients should
be informed about the signs and symptoms of serious skin manifestations
and use of the drug should be discontinued at the first appearance
of skin rash or any other sign of hypersensitivity.<br/>Pregnancy: In late pregnancy, as with other NSAIDs, INDOCIN
should be avoided because it may cause premature closure of the ductus
arteriosus.<br/>Ocular Effects: Corneal deposits and retinal disturbances, including
those of the macula, have been observed in some patients who had received
prolonged therapy with INDOCIN. The prescribing physician should be
alert to the possible association between the changes noted and INDOCIN.
It is advisable to discontinue therapy if such changes are observed.
Blurred vision may be a significant symptom and warrants a thorough
ophthalmological examination. Since these changes may be asymptomatic,
ophthalmologic examination at periodic intervals is desirable inpatients
where therapy is prolonged.<br/>Central Nervous System Effects: INDOCIN may aggravate depression or other psychiatric
disturbances, epilepsy, and parkinsonism, and should be used with
considerable caution in patients with these conditions. If severe
CNS adverse reactions develop, INDOCIN should be discontinued. INDOCIN may cause drowsiness; therefore, patients should
be cautioned about engaging in activities requiring mental alertness
and motor coordination, such as driving a car. INDOCIN may also cause
headache. Headache which persists despite dosage reduction requires
cessation of therapy with INDOCIN.
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| dailymed-drugs:120 |
Vinorelbine should be administered in carefully adjusted doses by or under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Patients treated with Vinorelbine should be frequently monitored for myelosuppression both during and after therapy. Granulocytopenia is dose-limiting. Granulocyte nadirs occur between 7 and 10 days after dosing with granulocyte count recovery usually within the following 7 to 14 days. Complete blood counts with differentials should be performed and results reviewed prior to administering each dose of Vinorelbine. Vinorelbine should not be administered to patients with granulocyte counts<1,000 cells/mm. Patients developing severe granulocytopenia should be monitored carefully for evidence of infection and/or fever. See DOSAGE AND ADMINISTRATION for recommended dose adjustments for granulocytopenia. Acute shortness of breath and severe bronchospasm have been reported infrequently, following the administration of Vinorelbine and other vinca alkaloids, most commonly when the vinca alkaloid was used in combination with mitomycin. These adverse events may require treatment with supplemental oxygen, bronchodilators, and/or corticosteroids, particularly when there is pre-existing pulmonary dysfunction. Reported cases of interstitial pulmonary changes and acute respiratory distress syndrome (ARDS), most of which were fatal, occurred in patients treated with single-agent Vinorelbine. The mean time to onset of these symptoms after vinorelbine administration was 1 week (range 3 to 8 days). Patients with alterations in their baseline pulmonary symptoms or with new onset of dyspnea, cough, hypoxia, or other symptoms should be evaluated promptly. Vinorelbine has been reported to cause severe constipation (e.g., Grade 3-4), paralytic ileus, intestinal obstruction, necrosis, and/or perforation. Some events have been fatal.<br/>Pregnancy: Vinorelbine may cause fetal harm if administered to a pregnant woman. A single dose of vinorelbine has been shown to be embryo- and/or fetotoxic in mice and rabbits at doses of 9 mg/mand 5.5 mg/m, respectively (one third and one sixth the human dose). At nonmaternotoxic doses, fetal weight was reduced and ossification was delayed. There are no studies in pregnant women. If Vinorelbine is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant during therapy with Vinorelbine.
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| dailymed-drugs:122 |
Hepatotoxicity:: Naltrexone has the capacity to cause hepatocellular injury when given in excessive doses. Naltrexone is contraindicated in acute hepatitis or liver failure, and its use in patients with active liver disease must be carefully considered in light of its hepatotoxic effects. The margin of separation between the apparently safe dose of naltrexone and the dose causing hepatic injury appears to be only five-fold or less. Naltrexone does not appear to be a hepatotoxin at the recommended doses. Patients should be warned of the risk of hepatic injury and advised to stop the use of naltrexone and seek medical attention if they experience symptoms of acute hepatitis. Evidence of the hepatotoxic potential of naltrexone is derived primarily from a placebo controlled study in which naltrexone hydrochloride was administered to obese subjects at a dose approximately five-fold that recommended for the blockade of opiate receptors (300 mg per day). In that study, 5 of 26 naltrexone recipients developed elevations of serum transaminases (i.e., peak ALT values ranging from a low of 121 to a high of 532; or 3 to 19 times their baseline values) after three to eight weeks of treatment. Although the patients involved were generally clinically asymptomatic and the transaminase levels of all patients on whom follow-up was obtained returned to (or toward) baseline values in a matter of weeks, the lack of any transaminase elevations of similar magnitude in any of the 24 placebo patients in the same study is persuasive evidence that naltrexone is a direct (i.e., not idiosyncratic) hepatotoxin. This conclusion is also supported by evidence from other placebo controlled studies in which exposure to naltrexone hydrochloride at doses above the amount recommended for the treatment of alcoholism or opiate blockade (50 mg/day) consistently produced more numerous and more significant elevations of serum transaminases than did placebo. Transaminase elevations in 3 of 9 patients with Alzheimer's Disease who received naltrexone hydrochloride (at doses up to 300 mg/day) for 5 to 8 weeks in an open clinical trial have been reported. Although no cases of hepatic failure due to naltrexone administration have ever been reported, physicians are advised to consider this as a possible risk of treatment and to use the same care in prescribing naltrexone as they would other drugs with the potential for causing hepatic injury.<br/>Unintended Precipitation of Abstinence:: To prevent occurrence of an acute abstinence syndrome, or exacerbation of a pre-existing subclinical abstinence syndrome, patients must be opioid-free for a minimum of 7 to 10 days before starting naltrexone. Since the absence of an opioid drug in the urine is often not sufficient proof that a patient is opioid-free, a naloxone challenge should be employed if the prescribing physician feels there is a risk of precipitating a withdrawal reaction following administration of naltrexone. The naloxone challenge test is described in the DOSAGE AND ADMINISTRATION section.<br/>Attempt to Overcome Blockade:: While naltrexone is a potent antagonist with a prolonged pharmacologic effect (24 to 72 hours), the blockade produced by naltrexone is surmountable. This is useful in patients who may require analgesia, but poses a potential risk to individuals who attempt, on their own, to overcome the blockade by administering large amounts of exogenous opioids. Indeed, any attempt by a patient to overcome the antagonism by taking opioids is very dangerous and may lead to a fatal overdose. Injury may arise because the plasma concentration of exogenous opioids attained immediately following their acute administration may be sufficient to overcome the competitive receptor blockade. As a consequence, the patient may be in immediate danger of suffering life endangering opioid intoxication (e.g., respiratory arrest, circulatory collapse). Patients should be told of the serious consequences of trying to overcome the opiate blockade
. There is also the possibility that a patient who had been treated with naltrexone will respond to lower doses of opioids than previously used, particularly if taken in such a manner that high plasma concentrations remain in the body beyond the time that naltrexone exerts its therapeutic effects. This could result in potentially life-threatening opioid intoxication (respiratory compromise or arrest, circulatory collapse, etc.). Patients should be aware that they may be more sensitive to lower doses of opioids after naltrexone treatment is discontinued.<br/>Ultra Rapid Opioid Withdrawal:: Safe use of naltrexone in rapid opiate detoxification programs has not been established .
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| dailymed-drugs:123 |
Pregnancy - Pregnancy Category D - Dexrazoxane was toxic to pregnant rats at doses of 2 mg/kg (1/80 the human dose on a mg/mbasis) and embryotoxic and teratogenic at 8 mg/kg (about 1/20 the human dose on a mg/mbasis) when given daily during the period of organogenesis. Teratogenic effects in the rat included imperforate anus, microphthalmia, and anophthalmia. In offspring allowed to develop to maturity, fertility was impaired in the male and female rats treated in utero during organogenesis at 8 mg/kg. In rabbits, doses of 5 mg/kg (about 1/16 the human dose on a mg/mbasis) daily during the period of organogenesis caused maternal toxicity and doses of 20 mg/kg (1/4 the human dose on a mg/mbasis) were embryotoxic and teratogenic. Teratogenic effects in the rabbit included several skeletal malformations such as short tail, rib and thoracic malformations, and soft tissue variations including subcutaneous, eye and cardiac hemorrhagic areas, as well as agenesis of the gallbladder and of the intermediate lobe of the lung. There is no adequate information about the use of Totect���in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
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| dailymed-drugs:125 |
Excessive use of an adrenergic aerosol should be discouraged, as it may lose effectiveness. Occasional patients have been reported to develop severe paradoxical airway resistance with repeated, excessive use of isoproterenol inhalation preparations . The cause of this is unknown. It is advis��able that in such instances the use of this preparation be discon��tinued immediately and alternative therapy instituted, since in the reported cases the patients did not respond to other forms of therapy until the drug was withdrawn. Deaths have been reported following excessive use of isoproterenol inhalation preparations, and the exact cause is unknown. Cardiac arrest was noted in several instances .
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| dailymed-drugs:126 |
BETA-BLOCKER WITHDRAWAL: Nicardipine is not a beta-blocker and therefore gives no protection against the dangers of abrupt beta-blocker withdrawal; any such withdrawal should be by gradual reduction of dose of beta-blocker.<br/>RAPID DECREASES IN BLOOD PRESSURE: No clinical events have been reported suggestive of a too rapid decrease in blood pressure with Cardene I.V. However, as with any antihypertensive agent, blood pressure lowering should be accomplished over as long a time as is compatible with the patient's clinical status.<br/>USE IN PATIENTS WITH ANGINA: Increases in frequency, duration, or severity of angina have been seen in chronic oral therapy with Cardene capsules. Induction or exacerbation of angina has been seen in less than 1% of coronary artery disease patients treated with Cardene I.V. The mechanism of this effect has not been established.<br/>USE IN PATIENTS WITH CONGESTIVE HEART FAILURE: Cardene I.V. reduced afterload without impairing myocardial contractility in preliminary hemodynamic studies of CHF patients. However, in vitroand in some patients, a negative inotropic effect has been observed. Therefore, caution should be exercised when using Cardene I.V., particularly in combination with a beta-blocker, in patients with CHF or significant left ventricular dysfunction.<br/>USE IN PATIENTS WITH PHEOCHROMOCYTOMA: Only limited clinical experience exists in use of Cardene I.V. for patients with hypertension associated with pheochromocytoma. Caution should therefore be exercised when using the drug in these patients.<br/>PERIPHERAL VEIN INFUSION SITE: To minimize the risk of peripheral venous irritation, it is recommended that the site of infusion of Cardene I.V. be changed every 12 hours.
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| dailymed-drugs:128 |
Pre-existing depression may emerge or worsen during use of benzodiazepines including lorazepam. Ativan (lorazepam) is not recommended for use in patients with
a primary depressive disorder or psychosis. Use of benzodiazepines, including lorazepam, both used alone and in combination with other CNS depressants, may lead to potentially fatal respiratory depression. Use of benzodiazepines, including lorazepam, may lead to physical and psychological dependence. As with all patients on CNS- depressant drugs, patients receiving lorazepam should be warned not to operate dangerous machinery or motor vehicles and that their tolerance for alcohol and other CNS depressants will be diminished.<br/>Physical and Psychological Dependence: The use of benzodiazepines, including lorazepam, may lead to physical and psychological dependence. The risk of dependence increases with higher doses and longer term use and is further increased in patients with a history of alcoholism or drug abuse or in patients with significant personality disorders. The dependence potential is reduced when lorazepam is used at the appropriate dose for short-term treatment. Addiction-prone individuals (such as drug addicts or alcoholics) should be under careful surveillance when receiving lorazepam or other psychotropic agents. In general, benzodiazepines should be prescribed for short periods only (e.g. 2- 4 weeks). Extension of the treatment period should not take place without reevaluation of the need for continued therapy. Continuous long-term use of product is not recommended. Withdrawal symptoms (e.g. rebound insomnia) can appear following cessation of recommended doses after as little as one week of therapy. Abrupt discontinuation of product should be avoided and a gradual dosage-tapering schedule followed after extended therapy. Abrupt termination of treatment may be accompanied by withdrawal symptoms. Symptoms reported following discontinuation of benzodiazepines include headache, anxiety, tension, depression, insomnia, restlessness, confusion, irritability, sweating, rebound phenomena, dysphoria, dizziness, derealization, depersonalization, hyperacusis, numbness/tingling of extremities, hypersensitivity to light, noise, and physical contact/perceptual changes, involuntary movements, nausea, vomiting, diarrhea, loss of appetite, hallucinations/delirium, convulsions/seizures, tremor, abdominal cramps, myalgia, agitation, palpitations, tachycardia, panic attacks, vertigo, hyperreflexia, short-term memory loss, and hyperthermia. Convulsions/seizures may be more common in patients with pre-existing seizure disorders or who are taking other drugs that lower the convulsive threshold such as antidepressants. There is evidence that tolerance develops to the sedative effects of benzodiazepines. Lorazepam may have abuse potential, especially in patients with a history of drug and/or alcohol abuse.
|
| dailymed-drugs:129 |
ERTACZO Cream, 2%, is not indicated for ophthalmic, oral or intravaginal use.
|
| dailymed-drugs:131 |
Ketoconazole Cream, 2% is not for opthalmic use. Ketoconazole Cream, 2% contains sodium sulfite anhydrous, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.
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| dailymed-drugs:132 |
Cardiac Failure: Sympathetic stimulation may be a vital component supporting circulatory function in patients with congestive heart failure, and its inhibition by beta-blockade may precipitate more severe failure. Although beta-blockers should be avoided in overt congestive heart failure, if necessary, Visken (pindolol) can be used with caution in patients with a history of failure who are well-compensated, usually with digitalis and diuretics. Beta-adrenergic blocking agents do not abolishthe inotropic action of digitalis on heart muscle.<br/>In Patients Without History of Cardiac Failure: In patients with latent cardiac insufficiency, continued depression of the myocardium with beta-blocking agents over a period of time can in some cases lead to cardiac failure. At the first sign or symptom of impending cardiac failure, patients should be fully digitalized and/or be given a diuretic, and the response observed closely. If cardiac failure continues, despite adequate digitalization and diuretic, Visken (pindolol) therapy should be withdrawn (gradually if possible).<br/>Exacerbation of Ischemic Heart Disease Following Abrupt Withdrawal: Hypersensitivity to catecholamines has been observed in patients withdrawn from beta-blocker therapy; exacerbation of angina and, in some cases, myocardial infarction have occurred after abrupt discontinuation of such therapy. When discontinuing chronically administered Visken (pindolol), particularly in patients with ischemic heart disease, the dosage should be gradually reduced over a period of 1-2 weeks and the patient should be carefully monitored. If angina markedly worsens or acute coronary insufficiency develops, Visken (pindolol) administration should be reinstituted promptly, at least temporarily, and other measures appropriate for the management of unstable angina should be taken. Patients should be warned against interruption or discontinuation of therapy without the physician's advice. Because coronary artery disease is common and may be unrecognized, it may be prudent not to discontinue Visken (pindolol) therapy abruptly even in patients treated only for hypertension.<br/>Nonallergic Bronchospasm (e.g., chronic bronchitis, emphysema) - Patients with Bronchospastic Diseases Should in General Not Receive Beta-Blockers: Visken (pindolol) should be administered with caution since it may block bronchodilation produced by endogenous or exogenous catecholamine stimulation of betareceptors.<br/>Major Surgery: Because beta blockade impairs the ability of the heart to respond to reflex stimuli and may increase the risks of general anesthesia and surgical procedures, resulting in protracted hypotension or low cardiac output, it has generally been suggested that such therapy should be gradually withdrawn several days prior to surgery. Recognition of the increased sensitivity to catecholamines of patients recently withdrawn from beta-blocker therapy, however, has made this recommendation controversial. If possible, beta-blockers should be withdrawn well before surgery takes place. In the event of emergency surgery, the anesthesiologist should be informed that the patient is on beta-blocker therapy. The effects of Visken (pindolol) can be reversed by administration of beta-receptor agonists such as isoproterenol, dopamine, dobutamine, or levarterenol. Difficulty in restarting and maintaining the heart beat has also been reported with beta-adrenergic receptor blocking agents.<br/>Diabetes and Hypoglycemia: Beta-adrenergic blockade may prevent the appearance of premonitory signs and symptoms (e.g., tachycardia and blood pressure changes) of acute hypoglycemia. This is especially important with labile diabetics. Beta-blockade also reduces the release of insulin in response to hyperglycemia; therefore, it may be necessary to adjust the dose of antidiabetic drugs.<br/>Thyrotoxicosis: Beta-adrenergic blockade may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-blockade which might precipitate a thyroid crisis.
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Dependence and Withdrawal Reactions, Including Seizures: Certain adverse clinical events, some life-threatening, are a direct consequence of physical dependence to alprazolam. These include a spectrum of withdrawal symptoms; the most important is seizure . Even after relatively short-term use at doses of���4 mg/day, there is some risk of dependence. Spontaneous reporting system data suggest that the risk of dependence and its severity appear to be greater in patients treated with doses greater than 4 mg/day and for long periods (more than 12 weeks). However, in a controlled post-marketing discontinuation study of panic disorder patients who received alprazolam tablets,the duration of treatment (3 months compared to 6 months) had no effect on the ability of patients to taper to zero dose. In contrast, patients treated with doses of alprazolam tablets greater than 4 mg/day had more difficulty tapering to zero dose than those treated with less than 4 mg/day. Relapse or return of illness was defined as a return of symptoms characteristic of panic disorder (primarily panic attacks) to levels approximately equal to those seen at baseline before active treatment was initiated. Rebound refers to a return of symptoms of panic disorder to a level substantially greater in frequency, or more severe in intensity than seen at baseline. Withdrawal symptoms were identified as those which were generally not characteristic of panic disorder and which occurred for the first time more frequently during discontinuation than at baseline. The rate of relapse, rebound, and withdrawal in patients with panic disorder who received alprazolam extended-release tablets has not been systematically studied. Experience in randomized placebo-controlled discontinuation studies of patients with panic disorder who received alprazolam tablets showed a high rate of rebound and withdrawal symptoms compared to placebo treated patients. In a controlled clinical trial in which 63 patients were randomized to alprazolam tablets and where withdrawal symptoms were specifically sought, the following were identified as symptoms of withdrawal: heightened sensory perception, impaired concentration, dysosmia, clouded sensorium, paresthesias, muscle cramps, muscle twitch, diarrhea, blurred vision, appetite decrease, and weight loss. Other symptoms, such as anxiety and insomnia, were frequently seen during discontinuation, but it could not be determined if they were due to return of illness, rebound, or withdrawal. In two controlled trials of 6 to 8 weeks duration where the ability of patients to discontinue medication was measured, 71%-93% of patients treated with alprazolam tablets tapered completely off therapy compared to 89%-96% of placebo treated patients. In a controlled post-marketing discontinuation study of panic disorder patients treated with alprazolam tablets, the duration of treatment (3 months compared to 6 months) had no effect on the ability of patients to taper to zero dose. Seizures were reported for three patients in panic disorder clinical trials with alprazolam extended-release tablets. In two cases, the patients had completed 6 weeks of treatment with alprazolam extended-release tablets 6 mg/day before experiencing a single seizure. In one case, the patient abruptly discontinued alprazolam extended-release tablets, and in both cases, alcohol intake was implicated. The third case involved multiple seizures after the patient completed treatment with alprazolam extended-release tablets 4 mg/day and missed taking the medication on the first day of taper. All three patients recovered without sequelae. Seizures have also been observed in association with dose reduction or discontinuation of alprazolam tablets, the immediate release form of alprazolam. Seizures attributable to alprazolam tablets were seen after drug discontinuance or dose reduction in 8 of 1980 patients with panic disorder or in patients participating in clinical trials where doses of alprazolam tablets greater than 4 mg/day for over 3 months were permitted. Five of these cases clearly occurred during abrupt dose reduction, or discontinuation from daily doses of 2 to 10 mg. Three cases occurred in situations where there was not a clear relationship to abrupt dose reduction or discontinuation. In one instance, seizure occurred after discontinuation from a single dose of 1 mg after tapering at a rate of 1 mg every three days from 6 mg daily. In two other instances, the relationship to taper is indeterminate; in both of these cases the patients had been receiving doses of 3 mg daily prior to seizure. The duration of use in the above 8 cases ranged from 4 to 22 weeks. There have been occasional voluntary reports of patients developing seizures while apparently tapering gradually from alprazolam tablets. The risk of seizure seems to be greatest 24-72 hours after discontinuation .<br/>Status Epilepticus: The medical event voluntary reporting system shows that withdrawal seizures have been reported in association with the discontinuation of alprazolam tablets. In most cases, only a single seizure was reported; however, multiple seizures and status epilepticus were reported as well.<br/>Interdose Symptoms: Early morning anxiety and emergence of anxiety symptoms between doses of alprazolam tablets have been reported in patients with panic disorder taking prescribed maintenance doses. These symptoms may reflect the development of tolerance or a time interval between doses which is longer than the duration of clinical action of the administered dose. In either case, it is presumed that the prescribed dose is not sufficient to maintain plasma levels above those needed to prevent relapse, rebound, or withdrawal symptoms over the entire course of the interdosing interval.<br/>Risk of Dose Reduction: Withdrawal reactions may occur when dosage reduction occurs for any reason. This includes purposeful tapering, but also inadvertent reduction of dose (e.g., the patient forgets, the patient is admitted to a hospital). Therefore, the dosage of alprazolam extended-release tablets should be reduced or discontinued gradually .<br/>CNS Depression and Impaired Performance: Because of its CNS depressant effects, patients receiving alprazolam extended-release tablets should be cautioned against engaging in hazardous occupations or activities requiring complete mental alertness such as operating machinery or driving a motor vehicle. For the same reason, patients should be cautioned about the simultaneous ingestion of alcohol and other CNS depressant drugs during treatment with alprazolam extended-release tablets.<br/>Risk of Fetal Harm: Benzodiazepines can potentially cause fetal harm when administered to pregnant women. If alprazolam is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Because of experience with other members of the benzodiazepine class, alprazolam is assumed to be capable of causing an increased risk of congenital abnormalities when administered to a pregnant woman during the first trimester. Because use of these drugs is rarely a matter of urgency, their use duringthe first trimester should almost always be avoided. The possibility that a woman of childbearing potential may be pregnant at the time of institution of therapy should be considered. Patients should be advised that if they become pregnant during therapy or intend to become pregnant they should communicate with their physicians about the desirability of discontinuing the drug.<br/>Alprazolam Interaction with Drugs That Inhibit Metabolism via Cytochrome P450 3A: The initial step in alprazolam metabolism is hydroxylation catalyzed by cytochrome P450 3A (CYP3A). Drugs that inhibit this metabolic pathway may have a profound effect on the clearance of alprazolam. Consequently, alprazolam should be avoided in patients receiving very potent inhibitors of CYP3A. With drugs inhibiting CYP3A to a lesser but still significant degree, alprazolam should be used only with caution and consideration of appropriate dosage reduction. For some drugs, an interaction with alprazolam has been quantified with clinical data; for other drugs, interactions are predicted from in vitro data and/or experience with similar drugs in the same pharmacologic class. The following are examples of drugs known to inhibit the metabolism of alprazolam and/or related benzodiazepines, presumably through inhibition of CYP3A.<br/>Potent CYP3A Inhibitors:<br/>Azole antifungal agents: Ketoconazole and itraconazole are potent CYP3A inhibitors and have been shown in vivo to increase plasma alprazolam concentrations 3.98 fold and 2.70 fold, respectively. The co-administration of alprazolam with these agents is not recommended. Other azole-type antifungal agents should also be considered potent CYP3A inhibitors and the co-administration of alprazolam with them is not recommended . Drugs demonstrated to be CYP3A inhibitors on the basis of clinical studies involving alprazolam (caution and consideration of appropriate alprazolam dose reduction are recommended during co-administration with the following drugs): Nefazodone: Co-administration of nefazodone increased alprazolam concentration two-fold. Fluvoxamine: Co-administration of fluvoxamine approximately doubled the maximum plasma concentration of alprazolam, decreased clearance by 49%, increased half-life by 71%, and decreased measured psychomotor performance. Cimetidine: Co-administration of cimetidine increased the maximum plasma concentration of alprazolam by 86%, decreased clearance by 42%, and increased half-life by 16%.<br/>Other Drugs Possibly Affecting Alprazolam Metabolism:: Other drugs possibly affecting alprazolam metabolism by inhibition of CYP3A are discussed in the PRECAUTIONS section .
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Clinical Worsening and Suicide Risk: Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongestpredictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18-24) with major depressive disorder(MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older. The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs. placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table 1. No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide. It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression. All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms (see PRECAUTIONS and DOSAGE AND ADMINISTRATION - Discontinuation of Treatment with Paroxetine, for a description of the risks of discontinuation of paroxetine). Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers. Such monitoring should include daily observation by families and caregivers. Prescriptions for paroxetine should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.<br/>Screening Patients for Bipolar Disorder: A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that paroxetine is not approved for use in treating bipolar depression.<br/>Potential for Interaction With Monoamine Oxidase Inhibitors: In patients receiving another serotonin reuptake inhibitor drug in combination with a monoamine oxidase inhibitor (MAOI), there have been reports of serious, sometimes fatal, reactions including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma. These reactions have also been reported in patients who have recently discontinued that drug and have been started on an MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. While there are no human data showing such an interaction with paroxetine, limited animal data on the effects of combined use of paroxetine and MAOIs suggest that these drugs mayact synergistically to elevate blood pressure and evoke behavioral excitation. Therefore, it is recommended that paroxetine not be used in combination with an MAOI, or within 14 days of discontinuing treatment with an MAOI. At least 2 weeks should be allowed after stopping paroxetine before starting an MAOI.<br/>Serotonin Syndrome: The development of a potentially life-threatening serotonin syndrome may occur with use of paroxetine, particularly with concomitant use of serotonergic drugs (including triptans) and with drugs which impair metabolism of serotonin (including MAOIs). Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g.,hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The concomitant use of paroxetine with MAOIs intended to treat depression is contraindicated (see CONTRAINDICATIONS and WARNINGS���Potential for Interaction with Monoamine Oxidase Inhibitors). If concomitant use of paroxetine with a 5-hydroxytryptamine receptor agonist (triptan) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases (see PRECAUTIONS���Drug Interactions). The concomitant use of paroxetine with serotonin precursors (such as tryptophan) is not recommended (see PRECAUTIONS���Drug Interactions).<br/>Potential Interaction With Thioridazine: Thioridazine administration alone
produces prolongation of the QTc interval, which is associated with serious
ventricular arrhythmias, such as torsade de pointes���type arrhythmias, and sudden death. This effect appears to
be dose related. An
in vivo study suggests that drugs which inhibit CYP2D6, such as paroxetine,
will elevate plasma levels of thioridazine. Therefore, it is recommended that
paroxetine not be used in combination with thioridazine (see CONTRAINDICATIONS
and PRECAUTIONS).<br/>Usage in Pregnancy:<br/>Teratogenic Effects: Epidemiological studies have shown that infants born to women who had first trimester paroxetine exposure had an increased risk of cardiovascular malformations, primarily ventricular and atrial septal defects (VSDs and ASDs). In general, septal defects range from those that are symptomatic and may require surgery to those that are asymptomatic and may resolve spontaneously. If a patient becomes pregnant while taking paroxetine, she should be advised of the potential harm to the fetus. Unless the benefits of paroxetine to the mother justify continuing treatment, consideration should be given to either discontinuing paroxetine therapy or switching to another antidepressant (see PRECAUTIONS���Discontinuation of Treatment with Paroxetine). For women who intend to become pregnant or are in their first trimester of pregnancy, paroxetine should only be initiated after consideration of the other available treatment options. A study based on Swedish national registry data evaluated infants of 6,896 women exposed to antidepressants in early pregnancy (5,123 women exposed to SSRIs; including 815 for paroxetine). Infants exposed to paroxetine in early pregnancy had an increased risk of cardiovascular malformations (primarily VSDs and ASDs) compared to the entire registry population (OR 1.8; 95% confidence interval 1.1-2.8). The rate of cardiovascular malformations following early pregnancy paroxetine exposure was 2% vs. 1% in the entire registry population. Among the same paroxetine exposed infants, an examination of the data showed no increase in the overall risk for congenital malformations. A separate retrospective cohort study using US United Healthcare data evaluated 5,956 infants of mothers dispensed paroxetine or other antidepressants during the first trimester (n = 815 for paroxetine). This study showed a trend towards an increased risk for cardiovascular malformations for paroxetine compared to other antidepressants (OR 1.5; 95% confidence interval 0.8-2.9). The prevalence of cardiovascular malformations following first trimester dispensing was 1.5% for paroxetine vs. 1% for other antidepressants. Nine out of 12 infants with cardiovascular malformations whose mothers were dispensed paroxetine in the first trimester had VSDs. This study also suggested an increased risk of overall major congenital malformations (inclusive of the cardiovascular defects) for paroxetine compared to other antidepressants (OR 1.8; 95% confidence interval 1.2-2.8). The prevalence of all congenital malformations following first trimester exposure was 4% for paroxetine vs. 2% for other antidepressants.<br/>Animal Findings: Reproduction studies were performed at doses up to 50 mg/kg/day
in rats and 6 mg/kg/day in rabbits administered during organogenesis.
These doses are approximately 8 (rat) and 2 (rabbit) times the MRHD
on an mg/mbasis. These studies have revealed no evidence of teratogenic
effects. However, in rats, there was an increase in pup deaths during the
first 4 days of lactation when dosing occurred during the last trimester
of gestation and continued throughout lactation. This effect occurred at a
dose of 1 mg/kg/day or approximately one-sixth of the MRHD on an mg/mbasis.
The no-effect dose for rat pup mortality was not determined. The cause of
these deaths is not known.<br/>Nonteratogenic Effects: Neonates exposed to paroxetine hydrochloride and other SSRIs or serotonin and norepinephrine reuptake inhibitors (SNRIs), late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome (see WARNINGS���Potential for Interaction With Monoamine Oxidase Inhibitors). Infants exposed to SSRIs in late pregnancy may have an increased risk of persistent pulmonary hypertension of the newborn (PPHN). PPHN occurs in 1-2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality. In a retrospective case-control study of 377 women whose infants were born with PPHN and 836 women whose infants were born healthy, the risk for developing PPHN was approximately six-fold higher for infants exposed to SSRIs after the 20th week of gestation compared to infants who had not been exposed to antidepressants during pregnancy. There is currently no corroborative evidence regarding the risk for PPHN following exposure to SSRIs in pregnancy; this is the first study that has investigated the potential risk. The study did not include enough cases with exposure to individual SSRIs to determine if all SSRIs posed similar levels of PPHN risk. There have also been postmarketing reports of premature births in pregnant women exposed to paroxetine or other SSRIs. When treating a pregnant woman with paroxetine during the third trimester, the physician should carefully consider both the potential risks and benefits of treatment (see DOSAGE AND ADMINISTRATION). Physicians should note that in a prospective longitudinal study of 201 women with a history major depression who were euthymic at the beginning of pregnancy, women who discontinued antidepressant medication during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressant medication.
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Tardive Dyskinesia: Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with neuroleptic (antipsychotic) drugs. Although the prevalence of the syndrome appears to be the highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of neuroleptic treatment, which patients are likely to develop the syndrome. Whether neuroleptic drug products differ in their potential to cause tardive dyskinesia is unknown. Both the risk of developing the syndrome and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of neuroleptic drugs administered to the patient increase. However, the syndrome can develop although much less commonly, after relatively brief treatment periods at low doses. There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if neuroleptic treatment is withdrawn. Neuroleptic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying disease process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown. Given these considerations, neuroleptics should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic neuroleptic treatment should generally be reserved for patients who suffer from a chronic illness that, 1) is known to respond to neuroleptic drugs, and, 2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically. If signs and symptoms of tardive dyskinesia appear in a patient on neuroleptics, drug discontinuation should be considered. However, some patients may require treatment despite the presence of the syndrome. (For further information about the description of tardive dyskinesia and its clinical detection, please refer to the sections on PRECAUTIONS, Information for Patients and ADVERSE REACTIONS, Tardive Dyskinesia.)<br/>Neuroleptic Malignant Syndrome (NMS): A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmias). The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever and primary central nervous system (CNS) pathology. The management of NMS should include 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS. If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored, since recurrences of NMS have been reported. The use of this drug may impair the mental and physical abilities required for driving a car or operating heavy machinery. Potentiation of the effects of alcohol may occur with the use of this drug. Since there is no adequate experience in children who have received this drug, safety and efficacy in children have not been established.<br/>Usage In Pregnancy: The safety for the use of this drug during pregnancy has not been established; therefore, the possible hazards should be weighed against the potential benefits when administering this drug to pregnant patients.
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BEFORE THERAPY WITH CEFACLOR EXTENDED-RELEASE TABLETS IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEFACLOR, CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS. IF THIS PRODUCT IS TO BE GIVEN TO PENICILLIN-SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE CROSS-SENSITIVITY AMONG BETA-LACTAM ANTIBIOTICS HAS BEEN CLEARLY DOCUMENTED AND MAY OCCUR IN UP TO 10% OF PATIENTS WITH A HISTORY OF PENICILLIN ALLERGY. IF AN ALLERGIC REACTION TO CEFACLOR EXTENDED-RELEASE TABLETS OCCURS, DISCONTINUE THE DRUG. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE TREATMENT WITH EPINEPHRINE AND OTHER EMERGENCY MEASURES, INCLUDING OXYGEN, INTRAVENOUSFLUIDS, INTRAVENOUS ANTIHISTAMINES, CORTICOSTEROIDS, PRESSOR AMINES, AND AIRWAY MANAGEMENT, AS CLINICALLY INDICATED. Pseudomembranous colitis has been reported with nearly all antibacterial agents, including cefaclor, and may range from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents. Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth by clostridia. Studies indicate that a toxin produced by Clostridium difficile is a primary cause of "antibiotic-associated colitis." After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to discontinuation of the drug alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation and treatment with an antibacterial drug clinically effective against Clostridium difficile.
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Ribavirin tablets must not be used alone because ribavirin monotherapy is not effective for the treatment of chronic hepatitis C virus infection. The safety and efficacy of ribavirin tablets have only been established when used together with peginterferon alfa-2a (pegylated interferon alfa-2a, recombinant). Ribavirin tablets and peginterferon alfa-2a should be discontinued in patients who develop evidence of hepatic decompensation during treatment. There are significant adverse events caused by ribavirin tablets/peginterferon alfa-2a therapy, including severe depression and suicidal ideation, hemolytic anemia, suppression of bone marrow function, autoimmune and infectious disorders, pulmonary dysfunction, pancreatitis, and diabetes. The peginterferon alfa-2a package insert and MEDICATION GUIDE should be reviewed in their entirety prior to initiation of combination treatment for additional safety information.<br/>General: Treatment with ribavirin tablets and peginterferon alfa-2a should be administered under the guidance of a qualified physician and may lead to moderate to severe adverse experiences requiring dose reduction, temporary dose cessation or discontinuation of therapy.<br/>Pregnancy: Ribavirin may cause birth defects and/or death of the exposed fetus. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin has demonstrated significant teratogenic and/or embryocidal effects in all animal species in which adequate studies have been conducted. These effects occurred at doses as low as one twentieth of the recommended human dose of ribavirin. RIBAVIRIN TABLETS THERAPY SHOULD NOT BE STARTED UNLESS A REPORT OF A NEGATIVE PREGNANCY TEST HAS BEEN OBTAINED IMMEDIATELY PRIOR TO PLANNED INITIATION OF THERAPY. Patients should be instructed to use at least two forms of effective contraception during treatment and for six-months after treatment has been stopped. Pregnancy testing should occur monthly during ribavirin tablets therapy and for 6 months after therapy has stopped .<br/>Anemia: The primary toxicity of ribavirin is hemolytic anemia (hemoglobin<10 g/dL), which was observed in approximately 13% of all ribavirin tablets and peginterferon alfa-2a treated patients in clinical trials . The anemia associated with ribavirin tablets occurs within 1 to 2 weeks of initiation of therapy. BECAUSE THE INITIAL DROP IN HEMOGLOBIN MAY BE SIGNIFICANT, IT IS ADVISED THAT HEMOGLOBIN OR HEMATOCRIT BE OBTAINED PRETREATMENT AND AT WEEK 2 AND WEEK 4 OF THERAPY OR MORE FREQUENTLY IF CLINICALLY INDICATED. Patients should then be followed as clinically appropriate. Fatal and nonfatal myocardial infarctions have been reported in patients with anemia caused by ribavirin. Patients should be assessed for underlying cardiac disease before initiation of ribavirin therapy. Patients with pre-existing cardiac disease should have electrocardiograms administered before treatment, and should be appropriately monitored during therapy. If there is any deterioration of cardiovascular status, therapy should be suspended or discontinued . Because cardiac disease may be worsened by drug induced anemia, patients with a history of significant or unstable cardiac disease should not use ribavirin tablets .<br/>Hepatic Failure: Chronic hepatitis C (CHC) patients with cirrhosis may be at risk of hepatic decompensation and death when treated with alpha interferons, including peginterferon alfa-2a. Cirrhotic CHC patients coinfected with HIV receiving highly active antiretroviral therapy (HAART) and interferon alfa-2a with or without ribavirin appear to be at increased risk for the development of hepatic decompensation compared to patients not receiving HAART. In Study NR15961 (described as Study 6 in the peginterferon alfa-2a package insert), among 129 CHC/HIV cirrhotic patients receiving HAART, 14 (11%) of these patients across all treatment arms developed hepatic decompensation resulting in 6 deaths. All 14 patients were on NRTIs, including stavudine, didanosine, abacavir, zidovudine, and lamivudine. These small numbers of patients do not permit discrimination between specific NRTIs or the associated risk. During treatment, patients' clinical status and hepatic function should be closely monitored, and peginterferon alfa-2a treatment should be immediately discontinued if decompensation (Child-Pugh score���6) is observed .<br/>Hypersensitivity:: Severe acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, and anaphylaxis) have been rarely observed during alpha interferon and ribavirin therapy. If such reaction occurs, therapy with peginterferon alfa-2a and ribavirin should be discontinued and appropriate medical therapy immediately instituted. Serious skin reactions including vesiculobullous eruptions, reactions in the spectrum of Stevens Johnson Syndrome (erythema multiforme major) with varying degrees of skin and mucosal involvement andexfoliative dermatitis (erythroderma) have been rarely reported in patients receiving peginterferon alfa-2a with and without ribavirin. Patients developing signs or symptoms of severe skin reactions must discontinue therapy..<br/>Pulmonary: Pulmonary symptoms, including dyspnea, pulmonary infiltrates, pneumonitis and occasional cases of fatal pneumonia, have been reported during therapy with ribavirin and interferon. In addition, sarcoidosis or the exacerbation of sarcoidosis has been reported. If there is evidence of pulmonary infiltrates or pulmonary function impairment, the patient should be closely monitored, and if appropriate, combination ribavirin tablets/peginterferon alfa-2a treatment should be discontinued.<br/>Other: Ribavirin tablets and peginterferon alfa-2a therapy should be suspended in patients with signs and symptoms of pancreatitis, and discontinued in patients with confirmed pancreatitis. Ribavirin tablets should not be used in patients with creatinine clearance<50 mL/min . Ribavirin tablets must be discontinued immediately and appropriate medical therapy instituted if an acute hypersensitivity reaction (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) develops. Transient rashes do not necessitate interruption of treatment.
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Solutions containing sodium ions should be used with
great care, if at all, in patients with congestive heart failure,
severe renal insufficiency and in clinical states in which there exists
edema with sodium retention. Excessive administration
of potassium-free solutions may result in significant hypokalemia. In patients with diminished renal function, administration
of solutions containing sodium ions may result in sodium retention. The intravenous administration of these solutions
can cause fluid and/or solute overloading resulting in dilution of
serum electrolyte concentrations, overhydration, congested states
or pulmonary edema. The risk of dilutional
states is inversely proportional to the electrolyte concentrations
of administered parenteral solutions. The risk of solute overload
causing congested states with peripheral and pulmonary edema is directly
proportional to the electrolyte concentrations of such solutions.
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Hepatotoxicity: Hepatic failure resulting
in fatalities has occurred in patients receiving valproic acid. These incidents
usually have occurred during the first six months of treatment. Serious or
fatal hepatotoxicity may be preceded by non-specific symptoms such as malaise,
weakness, lethargy, facial edema, anorexia, and vomiting. In patients with
epilepsy, a loss of seizure control may also occur. Patients should be monitored
closely for appearance of these symptoms. Liver function tests should be
performed prior to therapy and at frequent intervals thereafter, especially
during the first six months. However, physicians should not rely totally
on serum biochemistry since these tests may not be abnormal in all instances,
but should alsoconsider the results of careful interim medical history and
physical examination. Caution should be observed when administering DEPAKOTE products
to patients with a prior history of hepatic disease. Patients on multiple
anticonvulsants, children, those with congenital metabolic disorders, those
with severe seizure disorders accompanied by mental retardation, and those
with organic brain disease may be at particular risk. Experience has indicated
that children under the age of two years are at a considerably increased risk
of developing fatal hepatotoxicity, especially those with the aforementioned
conditions. When DEPAKOTE is used in this patient group, it should be used
with extreme caution and as a sole agent. The benefits of therapy should
be weighed against the risks. Above this age group, experience in epilepsy
has indicated that the incidence of fatal hepatotoxicity decreases considerably
in progressively older patient groups. The drug should be discontinued immediately
in the presence of significant hepatic dysfunction, suspected or apparent.
In some cases, hepatic dysfunction has progressed in spite of discontinuation
of drug.<br/>Pancreatitis: Cases of life-threatening pancreatitis have been
reported in both children and adults receiving valproate. Some of the cases
have been described as hemorrhagic with rapid progression from initial symptoms
to death. Some cases have occurred shortly after initial use as well as after
several years of use.The rate based upon
the reported cases exceeds that expected in the general population and there
have been cases in which pancreatitis recurred after rechallenge with valproate.
In clinical trials, there were 2 cases of pancreatitis without alternative
etiology in 2416 patients, representing 1044 patient-yearsexperience. Patients
and guardians should be warned that abdominal pain, nausea, vomiting, and/or
anorexia can be symptoms of pancreatitis that require prompt medical evaluation.
If pancreatitis is diagnosed, valproate should ordinarily be discontinued.
Alternative treatment for the underlying medical condition should be initiated
as clinically indicated (see BOXED WARNING).<br/>Urea Cycle Disorders (UCD): Divalproex sodium is contraindicated in patients
with known urea cycle disorders. Hyperammonemic encephalopathy, sometimes
fatal, has been reported following initiation of valproate therapy in patients
with urea cycle disorders, a group of uncommon genetic abnormalities, particularly
ornithine transcarbamylase deficiency. Prior to the initiation of valproate
therapy, evaluation for UCD should be considered in the following patients:
1) those with a history of unexplained encephalopathy or coma, encephalopathy
associated with a protein load, pregnancy-related or postpartum encephalopathy,
unexplained mental retardation, or history of elevated plasma ammonia or glutamine;
2) those with cyclical vomiting and lethargy, episodic extreme irritability,
ataxia, low BUN, or protein avoidance; 3) those with a family history of UCD
or a family history of unexplained infant deaths (particularly males); 4)
thosewith other signs or symptoms of UCD. Patients who develop symptoms
of unexplained hyperammonemic encephalopathy while receiving valproate therapy
should receive prompt treatment (including discontinuation of valproate therapy)
and be evaluated for underlying urea cycle disorders (see CONTRAINDICATIONSand PRECAUTIONS).<br/>Somnolence in the Elderly: In a double-blind, multicenter trial of valproate
in elderly patients with dementia (mean age = 83 years), doses were increased
by 125 mg/day to a target dose of 20 mg/kg/day. A significantly higher
proportion of valproate patients had somnolence compared to placebo, and although
not statistically significant, there was a higher proportion of patients with
dehydration. Discontinuations for somnolence were also significantly higher
than with placebo. In some patients with somnolence (approximately one-half),
there was associated reduced nutritional intake and weight loss. There was
a trend for the patients who experienced these events to have a lower baseline
albumin concentration, lower valproate clearance, and a higher BUN. In elderly
patients, dosage should be increased more slowly and with regular monitoring
for fluid and nutritional intake, dehydration, somnolence, and other adverse
events. Dose reductions or discontinuation of valproate should be considered
in patients with decreased food or fluid intake and in patients with excessive
somnolence (see DOSAGE AND ADMINISTRATION).<br/>Thrombocytopenia: The frequency of adverse effects (particularly elevated
liver enzymes and thrombocytopenia [see PRECAUTIONS]) may be dose-related. In a clinical trial of DEPAKOTE as monotherapy
in patients with epilepsy, 34/126 patients (27%) receiving approximately 50 mg/kg/day
on average, had at least one value of platelets���75 x 10/L.
Approximately half of these patients had treatment discontinued, with return
of platelet counts to normal. In the remaining patients, platelet counts
normalized with continued treatment. In this study, the probability of thrombocytopenia
appeared to increase significantly at total valproate concentrations of���110��g/mL
(females) or���135��g/mL (males). The therapeutic benefit
which may accompany the higher doses should therefore be weighed against the
possibility of a greater incidence of adverse effects.<br/>Usage In Pregnancy: VALPROATE CAN PRODUCE TERATOGENIC EFFECTS. DATA
SUGGEST THAT THERE IS AN INCREASED INCIDENCE OF CONGENITAL MALFORMATIONS ASSOCIATED
WITH THE USE OF VALPROATE BY WOMEN WITH SEIZURE DISORDERS DURING PREGNANCY
WHEN COMPARED TO THE INCIDENCE IN WOMEN WITH SEIZURE DISORDERS WHO DO NOT
USE ANTIEPILEPTIC DRUGS DURING PREGNANCY, THE INCIDENCE IN WOMEN WITH SEIZURE
DISORDERS WHO USE OTHER ANTIEPILEPTIC DRUGS, AND THE BACKGROUND INCIDENCE
FOR THE GENERAL POPULATION. THEREFORE, VALPROATE SHOULD BE CONSIDERED FOR
WOMEN OF CHILDBEARING POTENTIAL ONLY AFTER THE RISKS HAVE BEEN THOROUGHLY
DISCUSSED WITH THE PATIENT AND WEIGHED AGAINST THE POTENTIAL BENEFITS OF TREATMENT. THERE ARE MULTIPLE REPORTS IN THE CLINICAL LITERATURE THAT
INDICATE THE USE OF ANTIEPILEPTIC DRUGS DURING PREGNANCY RESULTS IN AN INCREASED
INCIDENCE OF CONGENITAL MALFORMATIONS IN OFFSPRING. ANTIEPILEPTIC DRUGS,
INCLUDING VALPROATE, SHOULD BE ADMINISTERED TO WOMEN OF CHILDBEARING POTENTIAL
ONLY IF THEY ARE CLEARLY SHOWN TO BE ESSENTIAL IN THE MANAGEMENT OF THEIR
MEDICAL CONDITION. Antiepileptic drugs should not be
discontinued abruptly in patients in whom the drug is administered to prevent
major seizures because of the strong possibility of precipitating status epilepticus
with attendant hypoxia and threat to life. In individual cases where the
severity and frequency of the seizure disorder are such that the removal of
medication does not pose a serious threat to the patient, discontinuation
of the drug may be considered prior to and during pregnancy, although it cannot
be said with any confidence that even minor seizures do not pose some hazard
to the developing embryo or fetus.<br/>Human Data:<br/>Animal Data: Animal studies have demonstrated valproate-induced teratogenicity.
Increased frequencies of malformations, as well as intrauterine growth retardation
and death, have been observed in mice, rats, rabbits, and monkeys following
prenatal exposure to valproate. Malformations of the skeletal system are
the most common structural abnormalities produced in experimental animals,
but neural tube closure defects have been seen in mice exposed to maternal
plasma valproate concentrations exceeding 230��g/mL (2.3 times the upper
limit of the human therapeutic range) during susceptible periods of embryonic
development. Administration of an oral dose of 200 mg/kg/day or greater
(50% of the maximum human daily dose or greater on a mg/mbasis)
to pregnant rats during organogenesis produced malformations (skeletal, cardiac,
and urogenital) and growth retardation in the offspring. These doses resulted
in peak maternal plasma valproate levels of approximately 340��g/mL or
greater (3.4 times the upper limit of the human therapeutic range or greater).
Behavioral deficits have been reported in the offspring of rats given a dose
of 200 mg/kg/day throughout most of pregnancy. An oral dose of 350 mg/kg/day
(approximately 2 times the maximum human daily dose on a mg/mbasis)
produced skeletal and visceral malformations in rabbits exposed during organogenesis.
Skeletal malformations, growth retardation, and death were observed in rhesus
monkeys following administration of an oral dose of 200 mg/kg/day (equal to
the maximum human daily dose on a mg/mbasis) during organogenesis.
This dose resulted in peak maternal plasma valproate levels of approximately
280��g/mL (2.8 times the upper limit of the human therapeutic range).
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Clinical Worsening and Suicide Risk: Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a longstanding concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs(SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18 to 24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older. The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table 1. No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide. It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression. All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms (see PRECAUTIONS and DOSAGE AND ADMINISTRATION - Discontinuation of Treatment with Citalopram, for a description of the risks of discontinuation of citalopram). Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to healthcare providers. Such monitoring should include daily observation by families and caregivers. Prescriptions for citalopram should be written for the smallest quantity of capsules consistent with good patient management, in order to reduce the risk of overdose.<br/>Screening Patients for Bipolar Disorder:: A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that citalopram is not approved for use in treating bipolar depression.<br/>Potential for Interaction with Monoamine Oxidase Inhibitors: In patients receiving serotonin reuptake inhibitor drugs in combination with a monoamine oxidase inhibitor (MAOI), there have been reports of serious, sometimes fatal, reactions including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma. These reactions have also been reported in patients who have recently discontinued SSRI treatment and have been started on an MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. Furthermore, limited animal data on the effects of combined use of SSRIs and MAOIs suggest that these drugs may act synergistically to elevate blood pressure and evoke behavioral excitation. Therefore, it is recommended that citalopram should not be used in combination with an MAOI, or within 14 days of discontinuing treatment with an MAOI. Similarly, at least 14 days should be allowed after stopping citalopram before starting an MAOI.
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Do NOT add any alkalinizing substance, since dopamine
is inactivated in alkaline solution. Patients
who have been treated with monoamine oxidase (MAO) inhibitors prior
to administration of dopamine should receive substantially reduced
dosage of the latter. See PRECAUTIONS, Drug
Interactions, below. Additive medications should not be delivered via
this solution. Dopamine Hydrochloride
in 5% Dextrose Injection, USP contains sodium metabisulfite, a sulfite
that may cause allergic-type reactions including anaphylactic symptoms
and life-threatening or less severe asthmatic episodes in certain
susceptible people. The overall prevalence of sulfite sensitivity
in the general population is unknown and probably low. Sulfite sensitivity
is seen more frequently in asthmatic than in nonasthmatic people.
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THIS HIGHLY CONCENTRATED, READY-TO-USE
POTASSIUM CHLORIDE INJECTION IS INTENDED FOR THE MAINTENANCE OF
SERUM K+ LEVELS AND FOR POTASSIUM SUPPLEMENTATION IN FLUID
RESTRICTED PATIENTS WHO CANNOT ACCOMMODATE ADDITIONAL VOLUMES OF
FLUID ASSOCIATED WITH POTASSIUM SOLUTIONS OF LOWER
CONCENTRATION. TO AVOID POTASSIUM INTOXICATION, DO NOT INFUSE
THESE SOLUTIONS RAPIDLY. PATIENTS REQUIRING HIGHLY CONCENTRATED
SOLUTIONS SHOULD BE KEPT ON CONTINUOUS CARDIAC MONITORING AND
UNDERGO FREQUENT TESTING FOR SERUM POTASSIUM AND ACID-BASE BALANCE,
ESPECIALLY IF THEY RECEIVE DIGITALIS. In patients with
renal insufficiency, administration of potassium chloride may cause
potassium intoxication and life-threatening hyperkalemia. Administer intravenously only with a
calibrated infusion device at a slow, controlled rate. (See Dosage
and Administration). Because pain associated with peripheral
infusion of Potassium Chloride solution has been reported, whenever
possible, administration via a central route is recommended for
thorough dilution by the blood stream and avoidance of
extravasation. Highest concentrations (300 and 400 mEq/L) should be
exclusively administered via central route. The administration
of intravenous solutions can cause fluid and/or solute overload
resulting in dilution of serum electrolyte concentrations,
overhydration, congested states or pulmonary edema. The risk of
dilutional states is inversely proportional to the electrolyte
concentration. The risk of solute overload causing congested states with
peripheral and pulmonary edema is directly proportional to the
electrolyte concentration.
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Intravenous infusion of amino acids may induce a
rise in blood urea nitrogen (BUN), especially in patients with impaired
hepatic or renal function. Appropriate laboratory tests should be
performed periodically and infusion discontinued if BUN levels exceed
normal postprandial limits and continue to rise. It should be noted
that a modest rise in BUN normally occurs as a result of increased
protein intake. Administration of amino
acid solutions to a patient with hepatic insufficiency may result
in serum amino acid imbalances, metabolic alkalosis, prerenal azotemia,
hyperammonemia, stupor and coma. Administration
of amino acid solutions in the presence of impaired renal function
may augment an increasing BUN, as does any protein dietary component. Solutions containing sodium ion should be used
with great care, if at all, in patients with congestive heart failure,
severe renal insufficiency and in clinical states in which there exists
edema with sodium retention. Solutions
which contain potassium ion should be used with great care, if at
all, in patients with hyperkalemia, severe renal failure and in conditions
in which potassium retention is present. Solutions containing acetate ion should be used with great care
in patients with metabolic or respiratory alkalosis. Acetate should
be administered with great care in those conditions in which there
is an increased level or an impaired utilization of this ion, such
as severe hepatic insufficiency. Hyperammonemia
is of special significance in infants, as it can result in mental
retardation. Therefore, it is essential that blood ammonia levels
be measured frequently in infants. Instances
of asymptomatic hyperammonemia have been reported in patients without
overt liver dysfunction. The mechanisms of this reaction are not clearly
defined, but may involve genetic defects and immature or subclinically
impaired liver function. Aminosyn II
(an amino acid injection) contains sodium hydrosulfite, a sulfite
that may cause allergic-type reactions including anaphylactic symptoms
and life-threatening or less severe asthmatic episodes in certain
susceptible people. The overall prevalence of sulfite sensitivity
in the general population is unknown and probably low. Sulfite sensitivity
is seen more frequently in asthmatic than in nonasthmatic people. WARNING: This product contains aluminum that may be toxic.
Aluminum may reach toxic levels with prolonged parenteral administration
if kidney function is impaired. Premature neonates are particularly
at risk because their kidneys are immature, and they require largeamounts of calcium and phosphate solutions, which contain aluminum. Research indicates that patients with impaired kidney
function, including premature neonates, who receive parenteral levels
of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum
at levels associated with central nervous system and bone toxicity.
Tissue loading may occur even at lower rates of administration.
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Neuropsychiatric Adverse Events���Pediatric Patients 3 to 12 years of age: Gabapentin use in pediatric patients with epilepsy 3 to 12 years of age is associated with the occurrence of central nervous system related adverse events. The most significant of these can be classified into the following categories: 1) emotional lability (primarily behavioral problems), 2) hostility, including aggressive behaviors, 3) thought disorder, including concentration problems and change in school performance, and 4) hyperkinesia (primarily restlessness and hyperactivity). Among the gabapentin-treated patients, most of the events were mild to moderate in intensity. In controlled trials in pediatric patients 3 to 12 years of age the incidence of these adverse events was: emotional lability 6% (gabapentin-treated patients) vs 1.3% (placebo-treated patients); hostility 5.2% vs 1.3%; hyperkinesia 4.7% vs 2.9%; and thought disorder 1.7% vs 0%. One of these events, a report of hostility, was considered serious. Discontinuation of gabapentin treatment occurred in 1.3% of patientsreporting emotional lability and hyperkinesia and 0.9% of gabapentin-treated patients reporting hostility and thought disorder. One placebo-treated patient (0.4%) withdrew due to emotional lability.<br/>Withdrawal Precipitated Seizure, Status Epilepticus: Antiepileptic drugs should not be abruptly discontinued because of the possibility of increasing seizure frequency. In the placebo-controlled studies in patients>12 years of age, the incidence of status epilepticus in patients receiving gabapentin was 0.6% (3 of 543) versus 0.5% in patients receiving placebo (2 of 378). Among the 2074 patients>12 years of age treated with gabapentin across all studies (controlled and uncontrolled) 31 (1.5%) had status epilepticus. Of these, 14 patients had no prior history of status epilepticus either before treatment or while on other medications. Because adequate historical data are not available, it is impossible to say whether or not treatment with gabapentin is associated with a higheror lower rate of status epilepticus than would be expected to occur in a similar population not treated with gabapentin.<br/>Tumorigenic Potential: In standard preclinical in vivo lifetime carcinogenicity studies, an unexpectedly high incidence of pancreatic acinar adenocarcinomas was identified in male, but not female, rats. (See PRECAUTIONS: Carcinogenesis, Mutagenesis, Impairment of Fertility.) The clinical significance of this finding is unknown. Clinical experience during gabapentin's premarketing development provides no direct means to assessits potential for inducing tumors in humans. In clinical studies in adjunctive therapy in epilepsy comprising 2085 patient-years of exposure in patients>12 years of age, new tumors were reported in 10 patients (2 breast, 3 brain, 2 lung, 1 adrenal, 1 non-Hodgkin's lymphoma, 1 endometrial carcinoma in situ), and preexisting tumors worsened in 11 patients (9 brain, 1 breast, 1 prostate) during or up to 2 years following discontinuation of gabapentin. Without knowledge of the background incidence and recurrence in a similar population not treated with gabapentin, it is impossible to know whether the incidence seen in this cohort is or is not affected by treatment.<br/>Sudden and Unexplained Death in Patients With Epilepsy: During the course of premarketing development of gabapentin 8 sudden and unexplained deaths were recorded among a cohort of 2203 patients treated (2103 patient-years of exposure). Some of these could represent seizure-related deaths in which the seizure was not observed, e.g., at night. This represents an incidence of 0.0038 deaths per patient-year. Although this rate exceeds that expected in a healthy population matched for age and sex, it is within the range of estimates for the incidence of sudden unexplained deaths in patients with epilepsy not receiving gabapentin (ranging from 0.0005 for the general population of epileptics to 0.003 for a clinical trial population similar to that in the gabapentin program, to 0.005 for patients with refractory epilepsy). Consequently, whether these figures are reassuring or raise further concern depends on comparability of the populations reported upon to the gabapentin cohort and the accuracy of the estimates provided.
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Hepatic Injury: Severe hepatocellular injury, confirmed by rechallenge in at least one case, occurs rarely with labetalol therapy. The hepatic injury is usually reversible, but hepatic necrosis and death have been reported. Injury has occurred after both short- and long-term treatment and may be slowly progressive despite minimal symptomatology. Similar hepatic events have been reported with a related research compound, dilevalol HCl, including two deaths. Dilevalol HCl is one of the four isomers of labetalol HCl. Thus, for patients taking labetalol, periodic determination of suitable hepatic laboratory tests would be appropriate. Laboratory testing should be done at the very first symptom or sign of liver dysfunction (e.g., pruritus, dark urine, persistent anorexia, jaundice, right upper quadrant tenderness, or unexplained���flu-like���symptoms). If the patient has laboratory evidence of liver injury or jaundice, labetalol should be stopped and not restarted.<br/>Cardiac Failure: Sympathetic stimulation is a vital component supporting circulatory function in congestive heart failure. Beta-blockade carries a potential hazard of further depressing myocardial contractility and precipitating more severe failure. Although beta-blockers should be avoided in overt congestive heart failure, if necessary, labetalol can be used with caution in patients with a history of heart failure who are well compensated. Congestive heart failure has been observed in patients receiving labetalol HCl. Labetalol does not abolish the inotropic action of digitalis on heart muscle.<br/>In Patients Without a History of Cardiac Failure: In patients with latent cardiac insufficiency, continued depression of the myocardium with beta-blocking agents over a period of time can, in some cases, lead to cardiac failure. At the first sign or symptom of impending cardiac failure, patients should be fully digitalized and/or be given a diuretic, and the response should be observed closely. If cardiac failure continues despite adequate digitalization and diuretic, labetalol therapy should be withdrawn (gradually, if possible).<br/>Ischemic Heart Disease: Angina pectoris has not been reported upon labetalol discontinuation. However, following abrupt cessation of therapy with some beta-blocking agents in patients with coronary artery disease, exacerbations of angina pectoris and, in some cases, myocardial infarction have been reported. Therefore, such patients should be cautioned against interruption of therapy without the physician's advice. Even in the absence of overt angina pectoris, when discontinuation of labetalol is planned, the patient should be carefully observed and should be advised to limit physical activity. If angina markedly worsens or acute coronary insufficiency develops, labetalol administration should be reinstituted promptly, at least temporarily, and other measures appropriate for the management of unstable angina should be taken.<br/>Nonallergic Bronchospasm (e.g., Chronic Bronchitis and Emphysema): Since labetalol HCl at the usual intravenous therapeutic doses has not been studied in patients with nonallergic bronchospastic disease, it should not be used in such patients.<br/>Pheochromocytoma: Intravenous labetalol has been shown to be effective in lowering blood pressure and relieving symptoms in patients with pheochromocytoma; higher than usual doses may be required. However, paradoxical hypertensive responses have been reported in a few patients with this tumor; therefore, use caution when administering labetalol to patients with pheochromocytoma.<br/>Diabetes Mellitus and Hypoglycemia: Beta-adrenergic blockage may prevent the appearance of premonitory signs and symptoms (e.g., tachycardia) of acute hypoglycemia. This is especially important with labile diabetics. Beta-blockade also reduces the release of insulin in response to hyperglycemia; it may therefore be necessary to adjust the dose of antidiabetic drugs.<br/>Major Surgery: The necessity or desirability of withdrawing beta-blocking therapy before major surgery is controversial. Protracted severe hypotension and difficulty in restarting or maintaining a heartbeat have been reported with beta-blockers. The effect of labetalol's alpha-adrenergic activity has not been evaluated in this setting. Several deaths have occurred when labetalol HCl injection was used during surgery (including when used in cases to control bleeding). A synergism between labetalol and halothane anesthesia has been shown .<br/>Rapid Decreases of Blood Pressure: Caution must be observed when reducing severely elevated blood pressure. A number of adverse reactions, including cerebral infarction, optic nerve infarction, angina, and ischemic changes in the electrocardiogram, have been reported with other agents when severely elevated blood pressure was reduced over time courses of several hours to as long as 1 or 2 days. The desired blood pressure lowering should therefore be achieved over as long a period of time as is compatible with the patient's status.
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Syncope and���First-dose���Effect: Doxazosin, like other alpha-adrenergic blocking agents, can cause marked hypotension, especially in the upright position, with syncope and other postural symptoms such as dizziness. Marked orthostatic effects are most common with the first dose but can also occur when there is a dosage increase, or if therapy is interrupted for more than a few days. To decrease the likelihood of excessive hypotension and syncope, it is essential thattreatment be initiated with the 1 mg dose. The 2, 4, and 8 mg tablets are not for initial therapy. Dosage should then be adjusted slowly (see DOSAGE AND ADMINISTRATION section) with evaluations and increases in dose every two weeks to the recommended dose. Additional antihypertensive agents should be added with caution. Patients being titrated with doxazosin should be cautioned to avoid situations where injury could result should syncope occur, during both the day and night. In an early investigational study of the safety and tolerance of increasing daily doses of doxazosin in normotensives beginning at 1 mg/day, only 2 of 6 subjects could tolerate more than 2 mg/day without experiencing symptomatic postural hypotension. In another study of 24 healthy normotensive male subjects receiving initial doses of 2 mg/day of doxazosin, seven (29%) of the subjects experienced symptomatic postural hypotension between 0.5 and 6 hours after the first dose necessitating termination of the study. In this study, 2 of the normotensive subjects experienced syncope. Subsequent trials in hypertensive patients always began doxazosin dosing at 1 mg/day resulting in a 4% incidence of postural side effects at 1 mg/day with no cases of syncope. In multiple dose clinical trials in hypertension involving over 1500 hypertensive patients with dose titration every one to two weeks, syncope was reported in 0.7% of patients. None of these events occurred at the starting dose of 1 mg and 1.2% (8/664) occurred at 16 mg/day. In placebo-controlled clinical trials in BPH, 3 out of 665 patients (0.5%) taking doxazosin reported syncope. Two of the patients were taking 1 mg doxazosin, while one patient was taking 2 mg doxazosin when syncope occurred. In the open-label, long-term extension follow-up of approximately 450 BPH patients, there were 3 reports of syncope (0.7%). One patient was taking 2 mg, one patient was taking 8 mg, and one patient was taking 12 mg when syncope occurred. In a clinical pharmacology study, one subject receiving 2 mg experienced syncope. If syncope occurs, the patient should be placed in a recumbent position and treated supportively as necessary.<br/>Priapism: Rarely (probably less frequently than once in every several thousand patients), alphaantagonists, including doxazosin, have been associated with priapism (painful penile erection, sustained for hours and unrelieved by sexual intercourse or masturbation). Because this condition can lead to permanent impotence if not promptly treated, patients must be advised about the seriousness of the condition (see PRECAUTIONS, Information for Patients).
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Clinical Worsening and Suicide Risk: Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depressionand certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents and young adults (ages 18 to 24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older. The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD) or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs. placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table 1. No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide. It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression. All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worseningof depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms aresevere, abrupt in onset, or were not part of the patient's presenting symptoms. If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms . Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers. Such monitoring should include daily observation by families and caregivers. Prescriptions for citalopram hydrobromide tablets should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.<br/>Screening Patients for Bipolar Disorder: A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that citalopram hydrobromide tablets are not approved for use in treating bipolar depression.<br/>Potential for Interaction with Monoamine Oxidase Inhibitors: In patients receiving serotonin reuptake inhibitor drugs in combination with a monoamine oxidase inhibitor (MAOI), there have been reports of serious, sometimes fatal, reactions including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changesthat include extreme agitation progressing to delirium and coma. These reactions have also been reported in patients who have recently discontinued SSRI treatment and have been started on a MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. Furthermore, limited animal data on the effects of combined use of SSRI's and MAOI's suggest that these drugs may act synergistically to elevate blood pressure and evoke behavioral excitation. Therefore, it is recommended that citalopramhydrobromide should not be used in combination with a MAOI, or within 14 days of discontinuing treatment with a MAOI. Similarly, at least 14 days should be allowed after stopping citalopram hydrobromide before starting a MAOI.<br/>Serotonin Syndrome: The development of a potentially life-threatening serotonin syndrome may occur with SNRIs and SSRIs, including citalopram hydrobromide treatment, particularly with concomitant use of serotonergic drugs (including triptans) and with drugs which impair metabolism of serotonin (including MAOIs). Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomicinstability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The concomitant use of citalopram hydrobromide with MAOIs intended to treat depression is contraindicated If concomitant treatment of citalopram hydrobromide with a 5-hydroxytryptamine receptor agonist (triptan) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases . The concomitant use of citalopram hydrobromide with serotonin precursors (such as tryptophan) is not recommended .
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Neomycin can induce permanent sensorineural hearing loss
due to cochlear damage, mainly destruction of hair cells in the organ of Corti.
The risk of ototoxicity is greater with prolonged use. Therapy
with this product should be limited to 7 days of treatment. Neomycin
sulfate may cause cutaneous sensitization. A precise incidence of hypersensitivity
reactions (primarily skin rash) due to topical neomycin is not known. Discontinue
promptly if sensitization or irritation occurs. When
using neomycin-containing products to control secondary infection in the chronic
dermatoses, such as chronic otitis extema or stasis dermatitis, it should
be borne in mind that the skin in these conditions is more liable than is
normal skin to become sensitized to many substances, including neomycin. The
manifestation of sensitization to neomycin is usually a low-grade reddening
with swelling, dry scaling, and itching; it may be manifest simply as a failure
to heal. Periodic examination for such signs is advisable, and the patient
should be told to discontinue the product if they are observed. These symptoms
regress quickly on withdrawing the medication. Neomycin-containing applications
should be avoided for the patient thereafter.
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NOT FOR INJECTION.QUIXIN solution should not be injected subconjunctivally, nor should it be introduced directly into the anterior chamber of the eye. In patients receiving systemic quinolones, serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported, some following the first dose. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema (including laryngeal, pharyngeal or facial edema), airway obstruction, dyspnea, urticaria, and itching. If an allergic reaction to levofloxacin occurs, discontinue the drug. Serious acute hypersensitivity reactions may require immediate emergency treatment. Oxygen and airway management should be administered as clinically indicated.
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When used intravenously,
the following procedures should be undertaken to reduce the possibility
of venous thrombosis, phlebitis, local irritation, swelling, and,
rarely, vascular impairment; the solution should be injected slowly,
taking at least one minute for each 5 mg (1 mL) given; do not use
small veins, such as those on the dorsum of the hand or wrist; extreme
care should be taken to avoid intra-arterial administration or extravasation. Do not mix or
dilute diazepam injection with other solutions or drugs in syringe
or infusion flask. If it is not feasible to administer diazepam directly
IV, it may be injected slowly through the infusion tubing as close
as possible to the vein insertion. Extreme care must be used in administering diazepam injection, particularly
by the IV route, to the elderly, to very ill patients, and to those
with limited pulmonary reserve because of the possibility that apnea
and/or cardiac arrest may occur. Concomitant use of barbiturates,
alcohol or other central nervous system depressants increases depression
with increased risk of apnea. Resuscitative equipment including that
necessary to support respiration should be readily available. When diazepam is used with a narcotic analgesic, the dosage
of the narcotic should be reduced by at least one-third and administered
in small increments. In some cases the use of a narcotic may not be
necessary. Diazepam injection should not be
administered to patients in shock, coma, or in acute alcoholic intoxication
with depression of vital signs. As is true of most CNS-acting drugs,
patients receiving diazepam should be cautioned against engaging in
hazardous occupations requiring complete mental alertness, such as
operating machinery or driving a motor vehicle. Tonic status epilepticus has been precipitated in patients treated
with IV diazepam for petit mal status or petit mal variant status. Usage in Pregnancy: An increased risk of congenital malformations
associated with the use of minor tranquilizers (diazepam, meprobamate,
and chlordiazepoxide) during the first trimester of pregnancy has
been suggested in several studies. Because use of these drugs is rarely
a matter of urgency, their use during this period should almost always
be avoided. The possibility that a woman of childbearing potential
may be pregnant at the time of institution of therapy should be considered.
Patients should be advised that if they become pregnant during therapy
or intend to become pregnant they should communicate with their physicians
about the desirability of discontinuing the drug. In humans, measurable amounts of diazepam were found in
maternal and cord blood, indicating placental transfer of the drug.
Until additional information is available, diazepam injection is not
recommended for obstetrical use. Use in Children: Efficacy and safety
of parenteral diazepam has not been established in the neonate (30
days or less of age). Prolonged central nervous
system depression has been observed in neonates, apparently due to
inability to biotransform diazepam into inactive metabolites. In pediatric use, in order to obtain maximal clinical
effect with the minimum amount of drug and thus to reduce the risk
of hazardous side effects, such as apnea or prolonged periods of somnolence,
it is recommended that the drug be given slowly over a three-minute
period in a dosage not to exceed 0.25 mg/kg. After an interval of
15 to 30 minutes the initial dosage can be safely repeated. If, however,
relief of symptoms is not obtained after a third administration, adjunctive
therapy appropriate to the condition being treated is recommended. Withdrawal symptoms of the barbiturate type have occurred
after the discontinuation of benzodiazepines (see DRUG ABUSE AND DEPENDENCE section).
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Serious Cardiovascular Events:<br/>Sudden Death and Pre-Existing Structural Cardiac Abnormalities or Other Serious Heart Problems:<br/>Hypertension and other Cardiovascular Conditions: Stimulant medications cause a modest increase in average blood pressure (about 2 to 4 mmHg) and average heart rate (about 3 to 6 bpm), and individuals may have larger increases. While the mean changes alone would not be expected to have short-term consequences, all patients should be monitored for larger changes in heart rate and blood pressure. Caution is indicated in treating patients whose underlying medical conditions might be compromised by increases in blood pressure or heart rate, e.g., those with pre-existing hypertension, heart failure, recent myocardial infarction, or ventricular arrhythmia.<br/>Assessing Cardiovascular Status in Patients being Treated with Stimulant Medications: Children, adolescents, or adults who are being considered for treatment with stimulant medications should have a careful history (including assessment for a family history of sudden death or ventricular arrhythmia) and physical exam to assess for the presence of cardiac disease, and should receive further cardiac evaluation if findings suggest such disease (e.g., electrocardiogram and echocardiogram). Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during stimulant treatment should undergo a prompt cardiac evaluation.<br/>Psychiatric Adverse Events: Pre-Existing Psychosis���Administration of stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder. Bipolar Illness���Particular care should be taken in using stimulants to treat ADHD in patients with comorbid bipolar disorder because of concern for possible induction of a mixed/manic episode in such patients. Prior to initiating treatment with a stimulant, patients with comorbid depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including afamily history of suicide, bipolar disorder, and depression. Emergence of New Psychotic or Manic Symptoms���Treatment emergent psychotic or manic symptoms, e.g., hallucinations, delusional thinking, or mania in children and adolescents without a prior history of psychotic illness or mania can be caused by stimulants at usual doses. If such symptoms occur, consideration should be given to a possible causal role of the stimulant, and discontinuation of treatment may be appropriate. In a pooled analysis of multiple short-term, placebo-controlled studies, such symptoms occurred in about 0.1% (4 patients with events out of 3482 exposed to methylphenidate or amphetamine for several weeks at usual doses) of stimulant-treated patients compared to 0 in placebo-treated patients. Aggression���Aggressive behavior or hostility is often observed in children and adolescents with ADHD, and has been reported in clinical trials and the postmarketing experience of some medications indicated for the treatment of ADHD. Although there is no systematic evidence that stimulants cause aggressive behavior or hostility, patients beginning treatment for ADHD should be monitored for the appearance of or worsening of aggressive behavior or hostility.<br/>Long-Term Suppression of Growth: Careful follow-up of weight and height in children ages 7 to 10 years who were randomized to either methylphenidate or non-medication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medication treated children over 36 months (to the ages of 10 to 13 years), suggests that consistently medicated children (i.e., treatment for 7 days per week throughout the year) have a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over 3 years), without evidence of growth rebound during this period of development. Published data are inadequate to determine whether chronic use of amphetamines may cause a similar suppression of growth, however, it is anticipated that they likely have this effect as well. Therefore, growth should be monitored during treatment with stimulants, and patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.<br/>Seizures: There is some clinical evidence that stimulants may lower the convulsive threshold in patients with prior history of seizures, in patients with prior EEG abnormalities in absence of seizures, and, very rarely, in patients without a history of seizures and no prior EEG evidence of seizures. In the presence of seizures, the drug should be discontinued.<br/>Visual Disturbance: Difficulties with accommodation and blurring of vision have been reported with stimulant treatment. USE IN CHILDREN LESS THAN SIX YEARS OF AGE Methylin should not be used in children under six years, since safety and efficacy in this age group have not been established.
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The use of oral contraceptives
is associated with increased risks of several serious conditions including
venous and arterial thrombotic and thromboembolic events (such as
myocardial infarction, thromboembolism, stroke, and transient ischemic
attack), hepatic neoplasia, gallbladder disease, and hypertension,
although the risk of serious morbidity or mortality is very small
in healthy women without underlying risk factors. The risk of morbidity
and mortality increases significantly in the presence of other underlying
risk factors such as certain inherited or acquired thrombophilias,
hypertension, hyperlipidemias, obesity, diabetes, and surgery or trauma
with increased risk of thrombosis . Practitioners prescribing oral contraceptives should be familiar
with the following information relating to these risks. The information contained in
this package insert is principally based on studies carried out in
patients who used oral contraceptives with higher doses of estrogens
and progestogens than those in common use today. The effect of long-term
use of the oral contraceptives with lower doses of both estrogens
and progestogens remains to be determined. Throughout this labeling, epidemiological studies reported are of
two types: retrospective or case control studies and prospective or
cohort studies. Case control studies provide a measure of the relative
risk of disease, namely, a ratio of the incidence of a disease among
oral contraceptive users to that among nonusers. The relative risk
does not provide information on the actual clinical occurrence of
a disease. Cohort studies provide a measure of attributable risk,
which is the difference in the incidence of disease between oral contraceptive
users and nonusers. The attributable risk does provide information
about the actual occurrence of a disease in the population. For further
information, the reader is referred to a text on epidemiological methods.<br/>1. Thromboembolic Disorders and Other Vascular Problems: LYBREL is a non-cyclic
oral contraceptive that provides a low daily dose of estrogen and
progestin; however, LYBREL provides women with more hormonal exposure
on a yearly basis (13 additional weeks of hormone intake per
year) than conventional cyclic oral contraceptives containing the
same strength of synthetic estrogens and similar strength of progestins.<br/>a. Myocardial Infarction: An increased
risk of myocardial infarction has been attributed to oral contraceptive
use. This risk is primarily in smokers or women with other underlyingrisk factors for coronary-artery disease such as hypertension, hypercholesterolemia,
morbid obesity, and diabetes. The relative risk of heart attack for
current oral contraceptive users has been estimated to be two to six.
The risk is very low under the age of 30. Smoking in combination with oral contraceptive use has been shown
to contribute substantially to the incidence of myocardial infarction
in women in their mid-thirties or older with smoking accounting for
the majority of excess cases. Mortality rates associated with circulatory
disease have been shown to increase substantially in smokers over
the age of 35 and nonsmokers over the age of 40 (Figure 3) among women who use oral contraceptives. Oral contraceptives may compound the
effects of well-known risk factors, such as hypertension, diabetes,
hyperlipidemias, age, and obesity. In particular, some progestogens
are known to decrease HDL cholesterol and cause glucose intolerance,
while estrogens may create a state of hyperinsulinism. Oral contraceptives
have been shown to increase blood pressure among users (see section 9 in WARNINGS). Similar effects on risk factors have been associated with an increased
risk of heart disease. Oral contraceptives must be used with caution
in women with cardiovascular disease risk factors.<br/>b. Venous Thrombosis and Thromboembolism: An increased risk of venous thromboembolic and thrombotic
disease associated with the use of oral contraceptives is well established.
The risk of venous thrombotic and thromboembolic events is further
increased in women with conditions predisposing for venous thrombosis
and thromboembolism. Case control studies have found the relative
risk of users compared to non-users to be 3 for the first episode
of superficial venous thrombosis, 4 to 11 for deep-vein thrombosis
or pulmonary embolism, and 1.5 to 6 for women with predisposing conditions
for venous thromboembolic disease. Cohort studies have shown the relative
risk to be somewhat lower, about 3 for new cases and about 4.5 for
new cases requiring hospitalization. The approximate incidence of
deep-vein thrombosis and pulmonary embolism in users of lowdose (<0.05
mg ethinyl estradiol) combination oral contraceptives is up to 4 per
10,000 woman-years compared to 0.5-3 per 10,000 woman-years for non-users.
However, the incidence is less than that associated with pregnancy
(6 per 10,000 woman-years). The excess risk is highest during the
first year a woman ever uses a combined oral contraceptive. Venous
thromboembolism may be fatal. The risk of thromboembolic disease due
to oral contraceptives is not related to length of use and gradually
disappears after pill use is stopped. A two-to-four
fold increase in relative risk of postoperative thromboembolic complications
has been reported with the use of oral contraceptives. The relative
risk of venous thrombosis in women who have predisposing conditions
is twice that of women without such medical conditions. If feasible,
oral contraceptives should be discontinued at least four weeks prior
to and for two weeks after elective surgery of a type associated with
an increase in risk of thromboembolism and during and following prolonged
immobilization. Since the immediate post-partum period is also associated
with an increased risk of thromboembolism, oral contraceptives should
be started no earlier than four weeks after delivery in women who
elect not to breast-feed, or after a midtrimester pregnancy termination.<br/>c. Cerebrovascular Diseases: Oral contraceptives
have been shown to increase both the relative and attributable risks
of cerebrovascular events (thrombotic and hemorrhagic strokes), although,
in general, the risk is greatest among older (>35 years), hypertensive
women who also smoke. Hypertension was found to be a risk factor for
both users and nonusers, for both types of strokes, while smoking
interacted to increase the risk for hemorrhagic strokes. Transient
ischemic attacks have also been associated with oral contraceptive
use. In a large study, the relative risk of thrombotic strokes has been
shown to range from 3 for normotensive users to 14 for users with
severe hypertension. The relative risk of hemorrhagic stroke is reported
to be 1.2 for nonsmokers who used oral contraceptives, 2.6 for smokers
who did not use oral contraceptives, 7.6 for smokers who used oral
contraceptives, 1.8 for normotensive users and 25.7 for users with
severe hypertension. The attributable risk is also greater in older
women. Oral contraceptives also increase the risk for stroke in women
with other underlying risk factors such as certain inherited or acquired
thrombophilias. Women with migraine (particularly migraine/headaches
with focal neurological symptoms such as aura) who take combination
oral contraceptives may be at an increased risk of stroke.<br/>d. Dose-Related Risk of Vascular Disease From Oral Contraceptives: A positive
association has been observed between the amount of estrogen and progestogen
in oral contraceptives and the risk of vascular disease. A decline
in serum high-density lipoproteins (HDL) has been reported with many
progestational agents. A decline in serum high-density lipoproteins
has been associated with an increased incidence of ischemic heart
disease. Because estrogens increase HDL cholesterol, the net effect
of an oral contraceptive depends on a balance achieved between doses
of estrogen and progestogen and the nature and absolute amount of
progestogen used in the contraceptive. The amount of both hormones
should be considered in the choice of an oral contraceptive. Minimizing exposure
to estrogen and progestogen is in keeping with good principles of
therapeutics. For any particular estrogen/progestogen combination,
the dosage regimen prescribed should be one which contains the least
amount of estrogen and progestogen that is compatible with a low failure
rate and the needs of the individual patient. New acceptors of oral
contraceptive agents should be started on preparations containing
the lowest estrogen content which is judged appropriate for the individual
patient.<br/>e. Persistence of Risk of Vascular Disease: There are
two studies which have shown persistence of risk of vascular disease
for ever-users of oral contraceptives. In a study in the United States,
the risk of developing myocardial infarction after discontinuing oral
contraceptives persisted for at least 9 years for women 40-49 years
who had used oral contraceptives for five or more years, but this
increased risk was not demonstrated in other age groups. In another study
in Great Britain, the risk of developing cerebrovascular disease persisted
for at least 6 years after discontinuation of oral contraceptives,
although excess risk was very small. However, both studies were performed
with oral contraceptive formulations containing 0.05 mg or higher
of estrogens.<br/>2. Estimates of Mortality From Contraceptive Use: One study gathered
data from a variety of sources which have estimated the mortality
rate associated with different methods of contraception at different
ages (Table 3). These estimates include
the combined risk of death associated with contraceptive methods plus
the risk attributable to pregnancy in the event of method failure.Each method of contraception has its specific benefits and risks.
The study concluded that with the exception of oral contraceptive
users 35 and older who smoke and 40 and older who do not smoke, mortality
associated with all methods of birth control is less than that associated
with childbirth. The observation of a possible increase in risk of
mortality with age for oral contraceptive users is based on data gathered
in the 1970's���but not reported until 1983. However,
current clinical practice involves the use of lower estrogen dose
formulations combined with careful restriction of oral contraceptive
use to women who do not have the various risk factors listed in this
labeling. Because of these changes in practice, and also because of some limited
new data which suggest that the risk of cardiovascular disease with
the use of oral contraceptives may now be less than previously observed,
the Fertility and Maternal Health Drugs Advisory Committee was asked
to review the topic in 1989. The Committee concluded that although
cardiovascular disease risks may be increased with oral contraceptive
use after age 40 in healthy nonsmoking women (even with the newer
low-dose formulations), there are greater potential health risks associated
with pregnancy inolder women and with the alternative surgical and
medical procedures which may be necessary if such women do not have
access to effective and acceptable means of contraception. Therefore, the Committee
recommended that the benefits of oral contraceptive use by healthy
nonsmoking women over 40 may outweigh the possible risks. Of course,
older women, as all women who take oral contraceptives, should take
the lowest possible dose formulation that is effective.<br/>3. Carcinoma of the Reproductive Organs and Breasts: Numerous epidemiological studies have examined the
association between the use of oral contraceptives and the incidence
of breast and cervical cancer. The risk of
having breast cancer diagnosed may be slightly increased among current
and recent users of combination oral contraceptives. However, this
excess risk appears to decrease over time after combination oral contraceptive
discontinuation and by 10 years after cessation the increased risk
disappears. Some studies report an increased risk with duration of
use while other studies do not and no consistent relationships have
been found with dose or type of steroid. Some studies have reported
a small increase in risk for women who first use combination oral
contraceptives at a younger age. Most studies show a similar pattern
of risk with combination oral contraceptive use regardless of a woman's
reproductive history or her family breast cancer history. Breast cancers diagnosed
in current or previous oral contraceptive users tend to be less clinically
advanced than in nonusers. Women with known or suspected carcinoma of the breast or personal
history of breast cancer should not use oral contraceptives because
breast cancer is usually a hormonally sensitive tumor. Some studies suggest
that oral contraceptive use has been associated with an increase in
the risk of cervical intraepithelial neoplasia or invasive cervical
cancer in some populations of women. However, there continues to be
controversy about the extent to which such findings may be due to
differences in sexual behavior and other factors. In spite of many studies of the relationship between combination
oral contraceptive use and breast and cervical cancers, a cause-and-effect
relationship has not been established. Endometrial biopsies performed in a subset of subjects (Study 1;
n = 93) ages 18 to 49 years, after 6 to 12 months of use of LYBREL,
did not reveal any hyperplasias or malignancies. Endometrial malignancy
is rare in this age group, so change in the risk is unlikely to be
detected with a study of this size.<br/>4. Hepatic Neoplasia: Benign hepatic adenomas
are associated with oral contraceptive use, although the incidence
of these benign tumors is rare in the United States. Indirect calculations
have estimated the attributable risk to be in the range of 3.3 cases/100,000
for users, a risk that increases after four or more years of use.
Rupture of rare, benign, hepatic adenomas may cause death through
intra-abdominal hemorrhage. Studies from Britain have shown an increased risk of developing hepatocellular
carcinoma in long-term (>8 years) oral contraceptive user. However,
these cancers are extremely rare in the U.S. and the attributable
risk (the excess incidence) of liver cancers in oral contraceptive
users approaches less than one per million users.<br/>5. Ocular Lesions: There have been
clinical case reports of retinal thrombosis associated with the use
of oral contraceptives that may lead to partial or complete loss of
vision. Oral contraceptives should be discontinued if there is unexplained
partial or complete loss of vision; onset of proptosis or diplopia;
papilledema; or retinal vascular lesions. Appropriate diagnostic and
therapeutic measures should be undertaken immediately.<br/>6. Oral Contraceptive Use Before or During Early Pregnancy: Extensive epidemiological
studies have revealed no increased risk of birth defects in infants
born to women who have used oral contraceptives prior to pregnancy.
Studies also do not suggest a teratogenic effect, particularly insofar
as cardiac anomalies and limb-reduction defects are concerned, when
taken inadvertently during early pregnancy . The administration of
oral contraceptives to induce withdrawal bleeding should not be used
as a test for pregnancy. Oral contraceptives should not be used during
pregnancy to treat threatened or habitual abortion. The possibility of pregnancy should be considered in any patient
who may be experiencing symptoms of pregnancy, especially if she has
not adhered to the prescribed schedule. Oral-contraceptive use must
be discontinued if pregnancy is confirmed.<br/>7. Gallbladder Disease: Combination oral
contraceptives may worsen existing gallbladder disease and may accelerate
the development of this disease in previously asymptomatic women.
Earlier studies have reported an increased lifetime relative risk
of gallbladder surgery in users of oral contraceptives and estrogens.
More recent studies, however, have shown that the relative risk of
developing gallbladder disease among oral contraceptive users may
be minimal. The recent findings of minimal risk may be related to
the use of oral contraceptive formulations containing lower hormonal
doses of estrogens and progestogens.<br/>8. Carbohydrate and Lipid Metabolic Effects: Oral contraceptives
have been shown to cause glucose intolerance in a significant percentage
of users. Oral contraceptives containing greater than 0.075 mg of
estrogens cause hyperinsulinism, while lower doses of estrogen cause
less glucose intolerance. Progestogens increase insulin secretion
and create insulin resistance, this effect varying with different
progestational agents. However, in the nondiabetic woman, oral contraceptives
appear to have no effect on fasting blood glucose. Because of these
demonstrated effects, prediabetic and diabetic women should becarefully
observed while taking oral contraceptives. A small proportion of women will have persistent hypertriglyceridemia
while on the pill. As discussed earlier , changes in serum
triglycerides and lipoprotein levels have been reported in oral contraceptive
users.<br/>9. Elevated Blood Pressure: An increase in blood
pressure has been reported in women taking oral contraceptives and
this increase is more likely in older oral contraceptive users and
with continued use. Data from the Royal College of General Practitioners
and subsequent randomized trials have shown that the incidence of
hypertension increases with increasing quantities of progestogens. Women with a history
of hypertension or hypertension-related diseases, or renal disease
should be encouraged to use another method of contraception. If women
with hypertension elect to use oral contraceptives, they should be
monitored closely and if significant elevation of blood pressure occurs,
oral contraceptives should be discontinued .
For most women, elevated blood pressure will return to normal after
stopping oral contraceptives, and there is no difference in the occurrence
of hypertension among ever- and never-users.<br/>10. Headache: The onset or exacerbation
of migraine or development of headache with a new pattern that is
recurrent, persistent, or severe requires discontinuation of oral
contraceptives and evaluation of the cause.<br/>11. Bleeding Irregularities: When prescribing
LYBREL, the convenience of having no scheduled menstrual bleeding
should be weighed against the inconvenience of unscheduled breakthrough
bleeding and spotting. In Study 313-NA, 385/2,134 (18%) of women discontinued
prematurely due to bleeding that was reported either as an adverse
event or where bleeding was given as one of the reasons for discontinuation
(see INDICATIONS AND
USAGE, Clinical Studies). Figure 4 shows the percentage of
LYBREL subjects in study 313-NA by pill pack who experienced unscheduled
bleeding or spotting only (Defined as���No sanitary protection
required���). Figure 5 shows the percentage
of LYBREL subjects with complete bleeding data in Study 313-NA who
had 4 or more and 7 or more days of bleeding and/or spotting during
each pill pack cycle. During pill pack 2, 67% of subjects experienced
4 or more days of bleeding and/or spotting and 54% of these subjects
experienced 7 or more days of bleeding and/or spotting. During the
final cycle of use of LYBREL (pill pack 13), these percentages were
31% and 20%, respectively. As in any case of
bleeding irregularities, nonhormonal causes should be considered and
adequate diagnostic measures may be indicated to rule out pregnancy,
infection, malignancy, or other conditions. Some women may encounter post-pill amenorrhea or oligomenorrhea (possibly
with anovulation), especially when such a condition was preexistent.<br/>12. Ectopic Pregnancy: Ectopic as well
as intrauterine pregnancy may occur in contraceptive failures.
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There is a potential for cardiac risk of sexual activity in patients with preexisting cardiovascular disease. Therefore, treatments for erectile dysfunction, including VIAGRA, should not be generally used in men for whom sexual activity is inadvisable because of their underlying cardiovascular status. VIAGRA has systemic vasodilatory properties that resulted in transient decreases in supine blood pressure in healthy volunteers (mean maximum decrease of 8.4/5.5 mmHg), . While this normally would be expected to be of little consequence in most patients, prior to prescribing VIAGRA, physicians should carefully consider whether their patients with underlying cardiovascular disease could be affected adversely by such vasodilatory effects, especially in combination withsexual activity. Patients with the following underlying conditions can be particularly sensitive to the actions of vasodilators including VIAGRA���those with left ventricular outflow obstruction (e.g. aortic stenosis, idiopathic hypertrophic subaortic stenosis) and those with severely impaired autonomic control of blood pressure. There is no controlled clinical data on the safety or efficacy of VIAGRA in the following groups; if prescribed, this should be done with caution. Prolonged erection greater than 4 hours and priapism (painful erections greater than 6 hours in duration) have been reported infrequently since market approval of VIAGRA. In the event of an erection that persists longer than 4 hours, the patient should seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency could result. The concomitant administration of the protease inhibitor ritonavir substantially increases serum concentrations of sildenafil (11-fold increase in AUC). If VIAGRA is prescribed to patients taking ritonavir, caution should be used. Data from subjects exposed to high systemic levels of sildenafil are limited. Visual disturbances occurred more commonly at higher levels of sildenafil exposure. Decreased blood pressure, syncope, and prolonged erection were reported in some healthy volunteers exposed to high doses of sildenafil (200���800 mg). To decrease the chance of adverse events in patients taking ritonavir, a decrease in sildenafil dosage is recommended .
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LODOSYN (Carbidopa) has no antiparkinsonian effect when given alone. It is indicated for use with SINEMET (Carbidopa-Levodopa) or levodopa. LODOSYN (Carbidopa) does not decrease adverse reactions due to central effects of levodopa. When LODOSYN (Carbidopa) is to be given to carbidopa-naive patients who are being treated with levodopa alone, the two drugs should be given at the same time. At least twelve hours should elapse between the last dose of levodopa and initiation of therapy with LODOSYN (Carbidopa) and levodopa in combination. Start with no more than one-fifth (20%) to one-fourth (25%) of the previous daily dosage of levodopa when given without LODOSYN (Carbidopa). See the DOSAGE AND ADMINISTRATION section before initiating therapy. As with levodopa, concomitant administration of LODOSYN and levodopa may cause involuntary movements and mental disturbances. These reactions are thought to be due to increased brain dopamine following administration of levodopa. All patients should be observed carefully for the development of depression with concomitant suicidal tendencies. Patients with past or current psychoses should be treated with caution. Because LODOSYN (Carbidopa) permits more levodopa to reach the brain and, thus, more dopamine to be formed, dyskinesias may occur at lower levodopa dosages and sooner with concomitant use of LODOSYN (Carbidopa) and levodopa or carbidopa-levodopa combination products than with levodopa alone. The occurrence of dyskinesias may require levodopa dosage reduction. Levodopa, with or without LODOSYN, should be administered cautiously to patients with severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic, or endocrine disease. Care should be exercised in administering levodopa, with or without LODOSYN, to patients with a history of myocardial infarction who have residual atrial, nodal, or ventricular arrhythmias. In such patients, cardiac function should be monitored with particular care during the period of initial dosage adjustment, in a facility with provisions for intensive cardiac care. As with levodopa alone there is a possibility of upper gastrointestinal hemorrhage in patients with a history of peptic ulcer. Neuroleptic Malignant Syndrome (NMS): Sporadic cases of a symptom complex resembling NMS have been reported in association with dose reductions or withdrawal of certain antiparkinsonian agents such as levodopa, SINEMET (Carbidopa-Levodopa), or SINEMET CR (Carbidopa-Levodopa) Sustained-Release. Therefore, patients should be observed carefully when the dosage of levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics. NMS is an uncommon but life-threatening syndrome characterized by fever or hyperthermia. Neurological findings, including muscle rigidity, involuntary movements, altered consciousness, mental status changes; other disturbances, such as autonomic dysfunction, tachycardia, tachypnea, sweating, hyper- or hypotension; laboratory findings, such as creatine phosphokinase elevation, leukocytosis, myoglobinuria, and increased serum myoglobin, have been reported. The early diagnosis of this condition is important for the appropriate management of these patients. Considering NMS as a possible diagnosis and ruling out other acute illnesses (e.g., pneumonia, systemic infection, etc.) is essential. This may be especially complex if the clinical presentation includes both serious medical illness and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system (CNS) pathology. The management of NMS should include: 1) intensive symptomatic treatment and medical monitoring and 2) treatment of any concomitant serious medical problems for which specific treatments are available. Dopamine agonists, such as bromocriptine, and muscle relaxants, such as dantrolene, are often used in the treatment of NMS; however, their effectiveness has not been demonstrated in controlled studies.
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| dailymed-drugs:182 |
NOT FOR INJECTION INTO THE EYE. GENTAMICIN SULFATE OPHTHALMIC SOLUTION, USP is not for injection. It should never be injected subconjunctivally, nor should it be directly introduced into the anterior chamber of the eye.
|
| dailymed-drugs:186 |
Hypotension: Hypotension is the most common adverse effect seen with amiodarone I.V. In clinical trials, treatment-emergent, drug-related hypotension was reported as an adverse effect in 288 (16%) of 1836 patients treated with amiodarone I.V. Clinically significant hypotension during infusions was seen most often in the first several hours of treatment and was not dose related, but appeared to be related to the rate of infusion. Hypotension necessitating alterations in amiodarone I.V. therapy was reported in 3% of patients, with permanent discontinuation required in less than 2% of patients. Hypotension should be treated initially by slowing the infusion; additional standard therapy may be needed, including the following: vasopressor drugs, positive inotropic agents, and volume expansion. The initial rate of infusion should bemonitored closely and should not exceed that prescribed in DOSAGE AND ADMINISTRATION. In some cases, hypotension may be refractory resulting in fatal outcome .<br/>Bradycardia and AV Block: Drug-related bradycardia occurred in 90 (4.9%) of 1836 patients in clinical trials while they were receiving amiodarone I.V. for life-threatening VT/VF; it was not dose-related. Bradycardia should be treated by slowing the infusion rate or discontinuing amiodarone I.V. In some patients, inserting a pacemaker is required. Despite such measures, bradycardia was progressive and terminal in 1 patient during the controlled trials. Patients with a known predisposition to bradycardia or AV block should be treated with amiodarone I.V. in a setting where a temporary pacemaker is available.<br/>Liver Enzyme Elevations: Elevations of blood hepatic enzyme values - alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) - are seen commonly in patients with immediately life-threatening VT/VF. Interpreting elevated AST activity can be difficult because the values may be elevated in patients who have had recent myocardial infarction, congestive heart failure, or multiple electrical defibrillations. Approximately 54% of patients receiving amiodarone I.V. in clinical studies had baseline liver enzyme elevations, and 13% had clinically significant elevations. In 81% of patients with both baseline and on-therapy data available, the liver enzyme elevations either improved during therapy or remained at baseline levels. Baseline abnormalities in hepatic enzymes are not a contraindication to treatment. Acute, centrolobular confluent hepatocellular necrosis leading to hepatic coma, acute renal failure, and death has been associated with the administration of amiodarone I.V. at a much higher loading dose concentration and much faster rate of infusion than recommended in DOSAGE AND ADMINISTRATION. Therefore, the initial concentration and rate of infusion should be monitored closely and should not exceed that prescribed in DOSAGE AND ADMINISTRATION . In patients with life-threatening arrhythmias, the potential risk of hepatic injury should be weighed against the potential benefit of amiodarone I.V. therapy, but patients receiving amiodarone I.V. should be monitored carefully for evidence of progressive hepatic injury. Consideration should be given to reducing the rate of administration or withdrawing amiodarone I.V. in such cases.<br/>Proarrhythmia: Like all antiarrhythmic agents, amiodarone I.V. may cause a worsening of existing arrhythmias or precipitate a new arrhythmia. Proarrhythmia, primarily torsades de pointes (TdP), has been associated with prolongation by amiodarone I.V. of the QTc interval to 500 ms or greater. Although QTc prolongation occurred frequently in patients receiving amiodarone I.V., torsades de pointes or new-onset VF occurred infrequently (less than 2%). Patients should be monitored for QTc prolongation during infusion with amiodarone I.V. Combination of amiodarone with other antiarrhythmic therapy that prolongs the QTc should be reserved for patients with life-threatening ventricular arrhythmias who are incompletely responsive to a single agent. Fluoroquinolones, macrolide antibiotics, and azoles are known to cause QTc prolongation. There have been reports of QTc prolongation, with or without TdP, in patients taking amiodarone when fluoroquinolones, macrolide antibiotics, or azoles were administered concomitantly. (See Drug interactions, Other reported interactions with amiodarone:.) The need to coadminister amiodarone with any other drug known to prolong the QTc interval must be based on a careful assessment of the potential risks and benefits of doing so for each patient. A careful assessment of the potential risks and benefits of administering amiodarone I.V. must be made in patients with yhyroid dysfunction due to the possibility of arrhythmia breakthrough or exacerbation of arrhythmia, which may result in death, in these patients.<br/>Pulmonary Disorders:<br/>Early-onset pulmonary toxicity: There have been postmarketing reports of acute-onset (days to weeks) pulmonary injury in patients treated with amiodarone I.V. Findings have included pulmonary infiltrates and/or mass on x-ray, bronchospasm, wheezing, fever, dyspnea, cough, hemoptysis, and hypoxia. Some cases have progressed to respiratory failure and/or death.<br/>ARDS: Two percent (2%) of patients were reported to have adult respiratory distress syndrome (ARDS) during clinical studies involving 48 hours of therapy. ARDS is a disorder characterized by bilateral, diffuse pulmonary infiltrates with pulmonary edema and varying degrees of respiratory insufficiency. The clinical and radiographic picture can arise after a variety of lung injuries, such as those resulting from trauma, shock, prolonged cardiopulmonary resuscitation, and aspiration pneumonia, conditions present in many of the patients enrolled in the clinical studies. There have been postmarketing reports of ARDS in amiodarone I.V. patients. Amiodarone I.V. may play a role in causing or exacerbating pulmonary disorders in those patients. Postoperatively, occurrences of ARDS have been reported in patients receiving oral amiodarone therapy who have undergone either cardiac or noncardiac surgery. Although patients usually respond well to vigorous respiratory therapy, in rare instances the outcome has been fatal. Until further studies have been performed, it is recommended that FiOand the determinants of oxygen delivery to the tissues (e.g., SaO, PaO) be closely monitored in patients on amiodarone.<br/>Pulmonary fibrosis: Only 1 of more than 1000 patients treated with amiodarone I.V. in clinical studies developed pulmonary fibrosis. In that patient, the condition was diagnosed 3 months after treatment with amiodarone I.V., during which time she received oral amiodarone. Pulmonary toxicity is a well-recognized complication of long-termamiodarone use (see labeling for oral amiodarone).<br/>Loss of Vision: Cases of optic neuropathy and/or optic neuritis, usually resulting in visual impairment, have been reported in patients treated with oral amiodarone. In some cases, visual impairment has progressed to permanent blindness. Amiodarone I.V. is indicated for initiation of treatment and prophylaxis of frequently recurring ventricular fibrillation (VF) and hemodynamically unstable ventricular tachycardia (VT) in patients refractory to other therapy and can also be used to treat patients with VT/VF for whom oral amiodarone is indicated, but who are unable to take oral medication. Optic neuropathyand/or neuritis may occur at any time following initiation of therapy. A causal relationship to the drug has not been clearly established. If symptoms of visual impairment appear, such as changes in visual acuity and decreases in peripheral vision, prompt ophthalmic examination is recommended. Appearance of optic neuropathy and/or neuritis calls for re-evaluation of amiodarone therapy. The risks and complications of antiarrhythmic therapy with amiodarone must be weighed against its benefits in patients whose lives are threatened by cardiac arrhythmias. Regular ophthalmic examination, including fundoscopy and slit-lamp examination is recommended during administrations of amiodarone.<br/>Long-Term Use: See labeling for oral amiodarone. There has been limited experience in patients receiving amiodarone I.V. for longer than 3 weeks.<br/>Thyrotoxicosis: Amiodarone-induced hyperthyroidism may result in thyrotoxicosis and/or the possibility of arrhythmia breakthrough or aggravation. There have been reports of death associated with amiodarone-induced thyrotoxicosis. IF ANY NEW SIGNS F ARRHYTHMIA APPEAR, THE POSSIBILITY OF HYPERTHYROIDISM SHOULD BE CONSIDERED .<br/>Neonatal Hypo- or Hyperthyroidism: Although amiodarone use during pregnancy is uncommon, there have been a small number of published reports of congenital goiter/hypothyroidism and hyperthyroidism associated with its oral administration. If amiodarone I.V. is administered during pregnancy, the patient should be apprised of the potential hazard to the fetus.
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Rifampin has been shown to produce liver dysfunction. Fatalities associated with jaundice have occurred in patients with liver disease and in patients taking rifampin with other hepatotoxic agents. Patients with impaired liver function should only be given rifampin in cases of necessity and then with caution and under strict medical supervision. In these patients, careful monitoring of liver function, especially SGPT/ALT and SGOT/AST should be carried out prior to therapy and then every 2 to 4 weeks during therapy. If signs of hepatocellular damage occur, rifampin should be withdrawn. In some cases, hyperbilirubinemia resulting from competition between rifampin and bilirubin for excretory pathways of the liver at the cell level can occur in the early days of treatment. An isolated report showing a moderate rise in bilirubin and/or transaminase level is not in itself an indiction for interrupting treatment; rather, the decision should be made after repeating the tests, noting trends in the levels, and considering them in conjunction with the patient's clinical condition. Rifampin has enzyme-inducing properties, including induction of delta amino levulinic acid synthetase. Isolated reports have associated porphyria exacerbation with rifampin administration. The possibility of rapid emergence of resistant meningococci restricts the use of rifampin for injection to short-term treatment of the asymptomatic carrier state. Rifampin for injection is not to be used for the treatment of meningococcal disease.
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| dailymed-drugs:188 |
Amplification of the vasodilatory effects of isosorbide mononitrate by sildenafil can result in severe hypotension. The time course and dose dependence of this interaction have not been studied. Appropriate supportive care has not been studied, but it seems reasonable to treat this as a nitrate overdose, with elevation of the extremities and with central volume expansion. The benefits of ISMN in patients with acute myocardial infarction or congestive heart failure have not been established. Because the effects of isosorbide mononitrate are difficult to terminate rapidly, this drug is not recommended in these settings. If isosorbide mononitrate is used in these conditions, careful clinical or hemodynamic monitoring must be used to avoid the hazards of hypotension and tachycardia.
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Clinical Worsening and Suicide Risk���Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk ofdepression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long���standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short���term placebo���controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18���24) with major depressive disorder (MDD) and other psychiatric disorders. Short���term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older. The pooled analyses of placebo���controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short���term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo���controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short���term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug versus placebo), however, were relatively stable within age strata and across indications. These risk differences (drug���placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table 1. No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide. It is unknown whether the suicidality risk extends to longer���term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression. All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms . Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers. Such monitoring should include daily observation by families and caregivers. Prescriptions for SARAFEM should be written for the smallest quantity of capsules consistent with good patient management, in order to reduce the risk ofoverdose. It should be noted that SARAFEM is not approved for use in treating any indications in the pediatric population. Screening Patients for Bipolar Disorder���A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that SARAFEM is not approved for use in treating bipolar depression. Rash and Possibly Allergic Events���In 4 clinical trials for PMDD, 4% of 415 patients treated with SARAFEM reported rash and/or urticaria. None of these cases were classified as serious and 2 of 415 patients (both receiving 60 mg) were withdrawn from treatment because of rash and/or urticaria. In US fluoxetine clinical trials for conditions other than PMDD, 7% of 10,782 patients developed various types of rashes and/or urticaria. Among the cases of rash and/or urticaria reported in premarketing clinical trials, almost a third were withdrawn from treatment because of the rash and/or systemic signs or symptoms associated with the rash. Clinical findings reported in association with rash include fever, leukocytosis, arthralgias, edema, carpal tunnel syndrome, respiratory distress, lymphadenopathy, proteinuria, and mild transaminase elevation. Most patients improved promptly with discontinuation of fluoxetine and/or adjunctive treatment with antihistamines or steroids, and all patients experiencing these events were reported to recover completely. In premarketing clinical trials of fluoxetine for conditions other than PMDD, 2 patients are known to have developed a serious cutaneous systemic illness. In neither patient was there an unequivocal diagnosis, but one was considered to have a leukocytoclastic vasculitis, and the other, a severe desquamating syndrome that was considered variously to bea vasculitis or erythema multiforme. Other patients have had systemic syndromes suggestive of serum sickness. Since the introduction of fluoxetine for other indications, systemic events, possibly related to vasculitis and including lupus���like syndrome, have developed in patients with rash. Although these events are rare, they may be serious, involving the lung, kidney, or liver. Death has been reported to occur in association with these systemic events. Anaphylactoid events, including bronchospasm, angioedema, laryngospasm, and urticaria alone and in combination, have been reported. Pulmonary events, including inflammatory processes of varying histopathology and/or fibrosis, have been reported rarely. These events have occurred with dyspnea as the only preceding symptom. Whether these systemic events and rash have a common underlying cause or are due to different etiologies or pathogenic processes is not known. Furthermore, a specific underlying immunologic basis for these events has not been identified. Upon the appearance of rash or of other possibly allergic phenomena for which an alternative etiology cannot be identified, SARAFEM should be discontinued. Serotonin Syndrome���The development of a potentially life-threatening serotonin syndrome may occur with SNRIs and SSRIs, including SARAFEM treatment, particularly with concomitant use of serotonergic drugs (including triptans) and with drugs which impair metabolism of serotonin (including MAOIs). Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The concomitant use of SARAFEM with MAOIs intended to treat depression is contraindicated . If concomitant treatment of SARAFEM with a 5���hydroxytryptamine receptor agonist (triptan) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases . The concomitant use of SARAFEM with serotonin precursors (such as tryptophan) is not recommended . Potential Interaction with Thioridazine���In a study of 19 healthy male subjects, which included 6 slow and 13 rapid hydroxylators of debrisoquin, a single 25���mg oral dose of thioridazine produced a 2.4���fold higher Cand a 4.5���fold higher AUC for thioridazine in the slow hydroxylators compared with the rapid hydroxylators. The rate of debrisoquin hydroxylation is felt to depend on the level of CYP2D6 isozyme activity. Thus, this study suggests that drugs which inhibit CYP2D6, such as certain SSRIs, including fluoxetine, will produce elevated plasma levels ofthioridazine . Thioridazine administration produces a dose���related prolongation of the QTinterval, which is associated with serious ventricular arrhythmias, such as torsades de pointes���type arrhythmias, and sudden death. This risk is expected to increase with fluoxetine���induced inhibition of thioridazine metabolism .
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Additives may be
incompatible. Consult with pharmacist, if available. When introducing
additives, use aseptic techniques. Mix thoroughly. Do not store. Because of the
potential for life-threatening events, caution should be taken to ensure
that precipitates have not formed in any parenteral nutrient admixture. This product
contains sodium bisulfite, a sulfite that may cause allergic-type
reactions including anaphylactic symptoms and life-threatening or less
severe asthmatic episodes in certain susceptible people. The overall
prevalence of sulfite sensitivity in the general population is unknown
and probably low. Sulfite sensitivity is seen more frequently in
asthmatic than in nonasthmatic people. Safe, effective use
of parenteral nutrition requires a knowledge of nutrition as well as
clinical expertise in recognition and treatment of the complications
which can occur. Frequent evaluations and
laboratory determinations are necessary for proper monitoring of
parenteral nutrition. Studies should include blood sugar,
serum proteins, kidney and liver function tests, electrolytes, hemogram,
carbon dioxide content, serum osmolarities, blood cultures, and blood
ammonia levels. Administration of
amino acids in the presence of impaired renal function or
gastrointestinal bleeding may augment an already elevated blood urea
nitrogen. Patients with azotemia from any cause should not be infused
with amino acids without regard to total nitrogen intake. Administration of
intravenous solutions can cause fluid and/or solute overload resulting
in dilution of serum electrolyte concentrations, over-hydration,
congested states, or pulmonary edema. The risk of dilutional states is inversely proportional to the electrolyte concentrations of the
solutions. The risk of solute overload causing congested states with
peripheral and pulmonary edema is directly proportional to the
electrolyte concentrations of the solutions.
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| dailymed-drugs:192 |
Hypertension and Angina:<br/>Cardiac Failure: Sympathetic stimulation is a vital component supporting circulatory function in congestive heart failure, and beta blockade carries the potential hazard of further depressing myocardial contractility and precipitating more severe failure. In hypertensive and angina patients who have congestive heart failure controlled by digitalis and diuretics, metoprolol tartrate should be administered cautiously.<br/>In Patients Without a History of Cardiac Failure: Continued depression of the myocardium with beta-blocking agents over a period of time can, in some cases, lead to cardiac failure. At the first sign or symptom of impending cardiac failure, patients should be fully digitalized and/or given a diuretic. The response should be observed closely. If cardiac failure continues, despite adequate digitalization and diuretic therapy, metoprolol tartrate should be withdrawn.<br/>Bronchospastic Diseases: PATIENTS WITH BRONCHOSPASTIC DISEASES SHOULD, IN GENERAL, NOT RECEIVE BETA-BLOCKERS including metoprolol tartrate. Because of its relative betaselectivity, however, metoprolol tartrate may be used with caution in patients with bronchospastic disease who do not respond to, or cannot tolerate, other antihypertensive treatment. Since betaselectivity is not absolute, a beta-stimulating agent should be administered concomitantly, and the lowest possible dose of metoprolol tartrate should be used. In these circumstances it would be prudent initially to administer metoprolol tartrate in smaller doses three times daily, instead of larger doses two times daily, to avoid the higher plasma levels associated with the longer dosing interval.<br/>Major Surgery: The necessity or desirability of withdrawing beta-blocking therapy, including metoprolol tartrate, prior to major surgery is controversial; the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures. Metoprolol tartrate, like other beta-blockers, is a competitive inhibitor of beta-receptor agonists, and its effects can be reversed by administration of such agents, e.g., dobutamine or isoproterenol. However, such patients may be subject to protracted severe hypotension. Difficulty in restarting and maintaining the heart beat has also been reported with beta-blockers.<br/>Diabetes and Hypoglycemia: Metoprolol tartrate should be used with caution in diabetic patients if a beta-blocking agent is required. Beta-blockers may mask tachycardia occurring with hypoglycemia, but other manifestations such as dizziness and sweating may not be significantly affected.<br/>Pheochromocytoma: In patients known to have, or suspected of having, a pheochromocytoma, metoprolol tartrate is contraindicated . If metoprolol tartrate is required, it should be given in combination with an alpha blocker, and only after the alpha blocker has been initiated. Administration of beta blockers alone in the setting of pheochromocytoma has been associated with a paradoxical increase in blood pressure due to the attenuation of beta-mediated vasodilatation in skeletal muscle.<br/>Thyrotoxicosis: Beta-adrenergic blockade may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta blockade, which might precipitate a thyroid storm.<br/>Myocardial Infarction:<br/>Cardiac Failure: Sympathetic stimulation is a vital component supporting circulatory function, and beta blockade carries the potential hazard of depressing myocardial contractility and precipitating or exacerbating minimal cardiac failure. During treatment with metoprolol tartrate, the hemodynamic status of the patient should be carefully monitored. If heart failure occurs or persists despite appropriate treatment, metoprolol tartrate should be discontinued.<br/>Bradycardia: Metoprolol tartrate produces a decrease in sinus heart rate in most patients; this decrease is greatest among patients with high initial heart rates and least among patients with low initial heart rates. Acute myocardial infarction (particularly inferior infarction) may in itself produce significant lowering of the sinus rate. If the sinus ratedecreases to<40 beats/min, particularly if associated with evidence of lowered cardiac output, atropine (0.25 to 0.5 mg) should be administered intravenously. If treatment with atropine is not successful, metoprolol tartrate should be discontinued, and cautious administration of isoproterenol or installation of a cardiac pacemaker should be considered.<br/>AV Block: Metoprolol tartrate slows AV conduction and may produce significant first- (P-R interval���0.26 sec), second-, or third-degree heart block. Acute myocardial infarction also produces heart block. If heart block occurs, metoprolol tartrate should be discontinued and atropine (0.25 to 0.5 mg) should be administered intravenously. If treatment with atropine is not successful, cautious administration of isoproterenol or installation of a cardiac pacemaker should be considered.<br/>Hypotension: If hypotension (systolic blood pressure���90 mmHg) occurs, metoprolol tartrate should be discontinued, and the hemodynamic status of the patient and the extent of myocardial damage carefully assessed. Invasive monitoring of central venous, pulmonary capillary wedge, and arterial pressures may be required. Appropriate therapy with fluids, positive inotropic agents, balloon counterpulsation, or other treatment modalities should be instituted. If hypotension is associated with sinus bradycardia or AV block, treatment should be directed at reversing these (see above).<br/>Bronchospastic Diseases: PATIENTS WITH BRONCHOSPASTIC DISEASES SHOULD, IN GENERAL, NOT RECEIVE BETA-BLOCKERS including metoprolol tartrate. Because of its relative betaselectivity, metoprolol tartrate may be used with extreme caution in patients with bronchospastic disease. Because it is unknown to what extent beta-stimulating agents may exacerbate myocardial ischemia and the extent of infarction, these agents should not be used prophylactically. If bronchospasm not related to congestive heart failure occurs, metoprolol tartrate should be discontinued. A theophylline derivative or a betaagonist may be administered cautiously, depending on the clinical condition of the patient. Both theophylline derivatives and betaagonists may produce serious cardiac arrhythmias.
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| dailymed-drugs:193 |
Hypersensitivity to vitamin D may be one etiologic factor in infants with idiopathic hypercalcemia. In these cases vitamin D must be strictly restricted. Keep out of the reach of children.
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| dailymed-drugs:194 |
In patients with upper urinary tract bleeding, aminocaproic acid administration has been known to cause intrarenal obstruction in the form of glomerular capillary thrombosis or clots in the renal pelvis and ureters. For this reason, aminocaproic acid should not be used in hematuria of upper urinary tract origin, unless the possible benefits outweigh the risk. Subendocardial hemorrhages have been observed in dogs given intravenous infusions of 0.2 times the maximum human therapeutic dose of aminocaproic acid and in monkeys given 8 times the maximum human therapeutic dose of aminocaproic acid. Fatty degeneration of the myocardium has been reported in dogs given intravenous doses of aminocaproic acid at 0.8 to 3.3 times the maximum human therapeutic dose and in monkeys given intravenous doses of aminocaproic acid at 6 times the maximum human therapeutic dose. Rarely, skeletal muscle weakness with necrosis of muscle fibers has been reported following prolonged administration. Clinical presentation may range from mild myalgias with weakness and fatigue to a severe proximal myopathy with rhabdomyolysis, myoglobinuria, and acute renal failure. Muscle enzymes, especially creatine phosphokinase (CPK) are elevated. CPK levels should be monitored in patients on long-term therapy. Aminocaproic acid administration should be stopped if a rise in CPK is noted. Resolution follows discontinuation of aminocaproic acid; however, the syndrome may recur if aminocaproic acid is restarted. The possibility of cardiac muscle damage should also be considered when skeletal myopathy occurs. One case of cardiac and hepatic lesions observed in man has been reported. The patient received 2 g of aminocaproic acid every 6 hours for a total dose of 26 g. Death was due to continued cerebrovascular hemorrhage. Necrotic changes in the heart and liver were noted at autopsy.
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Hypersensitivity Reactions,
including Anaphylaxis: Serious hypersensitivity reactions, including some
with fatal outcome, have been reported with the BEXXAR therapeutic
regimen. Medications for the treatment of severe hypersensitivity
reactions should be available for immediate use. Patients who develop
severe hypersensitivity reactions should have infusions of the BEXXAR
therapeutic regimen discontinued and receive medical attention (see WARNINGS).<br/>Prolonged and Severe Cytopenias: The majority of patients who received the BEXXAR
therapeutic regimen experienced severe thrombocytopenia and neutropenia.
The BEXXAR therapeutic regimen should not be administered to patients
with>25% lymphoma marrow involvement and/or impaired bone marrow
reserve (see WARNINGS and ADVERSE REACTIONS).<br/>Pregnancy Category X: The BEXXAR therapeutic regimen can cause fetal harm
when administered to a pregnant woman.<br/>Special requirements: The BEXXAR therapeutic regimen (Tositumomab and
Iodine I 131 Tositumomab) contains a radioactive component and should
be administered only by physicians and other health care professionals
qualified by training in the safe use and handling of therapeutic
radionuclides. The BEXXAR therapeutic regimen should be administered
only by physicians who are in the process of being or have been certified
by GlaxoSmithKline in dose calculation and administration of the BEXXAR
therapeutic regimen.
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| dailymed-drugs:197 |
In patients with severe impairment of renal function, a test dose should be utilized (see Dosage and Administration). A second test dose may be tried if there is an inadequate response, but no more than two test doses should be attempted. The obligatory diuretic response following rapid infusion of 15% or 20% mannitol injection may further aggravate preexisting
hemoconcentration. Excessive loss of water and electrolytes may lead to serious imbalances. Serum sodium and potassium should be carefully monitored during mannitol administration. If urine output continues to decline during mannitol infusion, the patient's clinical status should be closely reviewed and
mannitol infusion suspended if necessary. Accumulation of mannitol may result in overexpansion of the extracellular fluid which may intensify existing or latent congestive heart failure. fxcessive loss of water and electrolytes may lead to serious imbalances. With continued administration of mannitol, loss of water
in excess of electrolytes can cause hypernatremia. Electrolyte measurements, including sodium and potassium, are therefore, of vital importance in monitoring the infusion of mannitol. Osmotic nephrosis, a reversible vacuolization of the tubules of unknown clinical significance, may proceed to severe irreversible
nephrosis, so that the renal function must be closely monitored during mannitol infusion.
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| dailymed-drugs:198 |
The replacement of a systemic corticosteroid with a topical corticosteroid can be accompanied by signs of adrenal insufficiency, and in addition some patients may experience symptoms of withdrawal, e.g., joint and/or muscular pain, lassitude, and depression. Patients previously treated for prolonged periods with systemic corticosteroids and transferred to topical corticosteroids should be carefully monitored for acute adrenal insufficiency in response to stress. In those patients who have asthma or other clinical conditions requiring long-term systemic corticosteroid treatment, too rapid a decrease in systemic corticosteroids may cause a severe exacerbation of their symptoms. The concomitant use of intranasal corticosteroids with other inhaled corticosteroids could increase the risk of signs or symptoms of hypercorticism and/or suppression of the HPA axis. A drug interaction study in healthy subjects has shown that ritonavir (a highly potent cytochrome P450 3A4 inhibitor) can significantly increase plasma fluticasone propionate exposure, resulting in significantly reduced serum cortisol concentrations . During postmarketing use, there have been reports of clinically significant drug interactions in patients receiving fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects including Cushing syndrome and adrenal suppression. Therefore, coadministration of fluticasone propionate and ritonavir is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects. Persons who are using drugs that suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in susceptible children or adults using corticosteroids. In children or adults who have not had these diseases or been properly immunized, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also notknown. If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If chickenpox develops, treatment with antiviral agents may be considered. Avoid spraying in eyes.
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| dailymed-drugs:200 |
Fetal/Neonatal Morbidity and Mortality: Drugs that act directly on the renin-angiotensin system can cause fetal and neonatal morbidity and death when administered to pregnant women. Several dozen cases have been reported in the world literature in patients who were taking angiotensin-converting enzyme inhibitors. When pregnancy is detected, Diovan should be discontinued as soon as possible. The use of drugs that act directly on the renin-angiotensin system during the second and third trimesters of pregnancy has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death. Oligohydramnios has also been reported, presumably resulting from decreased fetal renal function; oligohydramnios in this setting has beenassociated with fetal limb contractures, craniofacial deformation, and hypoplastic lung development. Prematurity, intrauterine growth retardation, and patent ductus arteriosus have also been reported, although it is not clear whether these occurrences were due to exposure to the drug. These adverse effects do not appear to have resulted from intrauterine drug exposure that has been limited to the first trimester. Mothers whose embryos and fetuses are exposed to an angiotensin II receptor antagonist only during the first trimester should be so informed. Nonetheless, when patients become pregnant, physicians should advise the patient to discontinue the use of valsartan as soon as possible. Rarely (probably less often than once in every thousand pregnancies), no alternative to a drug acting on the renin-angiotensin system will be found. In these rare cases, the mothers should be apprised of the potential hazards to their fetuses, and serial ultrasound examinations should be performed to assess the intra-amniotic environment. If oligohydramnios is observed, valsartan should be discontinued unless it is considered life-saving for the mother. Contraction stress testing (CST), a nonstress test (NST), or biophysical profiling (BPP) may be appropriate, depending upon the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Infants with histories of in utero exposure to an angiotensin II receptor antagonist should be closely observed for hypotension, oliguria, and hyperkalemia. If oliguria occurs, attention should be directed toward support of blood pressure and renal perfusion. Exchange transfusion or dialysis may be required as means of reversing hypotension and/or substituting for disordered renal function. No teratogenic effects were observed when valsartan was administered to pregnant mice and rats at oral doses up to 600 mg/kg/day and to pregnant rabbits at oral doses up to 10 mg/kg/day. However, significant decreases in fetal weight, pup birth weight, pup survival rate, and slight delays in developmental milestones were observed in studies in which parental rats were treated with valsartan at oral, maternally toxic (reduction in body weight gain and food consumption) doses of 600 mg/kg/day during organogenesis or late gestation and lactation. In rabbits, fetotoxicity (i.e., resorptions, litter loss, abortions, and low body weight) associated with maternal toxicity (mortality) was observed at doses of 5 and 10 mg/kg/day. The no observed adverse effect doses of 600, 200 and 2 mg/kg/day in mice, rats and rabbits represent 9, 6, and 0.1 times, respectively, the maximum recommended human dose on a mg/mbasis. (Calculations assume an oral dose of 320 mg/day and a 60-kg patient.)<br/>Hypotension in Volume- and/or Salt-Depleted Patients: Excessive reduction of blood pressure was rarely seen (0.1%) in patients with uncomplicated hypertension. In patients with an activated renin-angiotensin system, such as volume- and/or salt-depleted patients receiving high doses of diuretics, symptomatic hypotension may occur. This condition should be corrected prior to administration of Diovan, or the treatment should start under close medical supervision. If hypotension occurs, the patient should be placed in the supine position and, if necessary, given an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized.
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| dailymed-drugs:202 |
Myopathy/Rhabdomyolysis: Lovastatin, like other inhibitors of HMG-CoA reductase, occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase (CK) above ten times the upper limit of normal (ULN). Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. The risk of myopathy is increased by high levels of HMG-CoA reductase inhibitory activity in plasma. As with other HMG-CoA reductase inhibitors, the risk of myopathy/rhabdomyolysis is dose related. In a clinical study (EXCEL) in which patients were carefully monitored and some interacting drugs were excluded, there was one case of myopathy among 4,933 patients randomized to lovastatin 20 to 40 mg daily for 48 weeks, and 4 among 1,649 patients randomized to 80 mg daily. All patients starting therapy with lovastatin, or whose dose of lovastatin is being increased, should be advised of the risk of myopathy and told to report promptly any unexplained muscle pain, tenderness or weakness. Lovastatin therapy should be discontinued immediately if myopathy is diagnosed or suspected. In most cases, muscle symptoms and CK increases resolved when treatment was promptly discontinued. Periodic CK determinations may be considered in patients starting therapy with lovastatin or whose dose is being increased, but there is no assurance that such monitoring will prevent myopathy. Many of the patients who have developed rhabdomyolysis on therapy with lovastatin have had complicated medical histories, including renal insufficiency usually as a consequence of long-standing diabetes mellitus. Such patients merit closer monitoring. Therapy with lovastatin should be temporarily stopped a few days prior to elective major surgery and when any major medical or surgical condition supervenes. The risk of myopathy/rhabdomyolysis is increased by concomitant use of lovastatin with the following: Potent inhibitors of CYP3A4: Lovastatin, like several other inhibitors of HMG-CoA reductase, is a substrate of cytochrome P450 3A4 (CYP3A4). When lovastatin is used with a potent inhibitor of CYP3A4, elevated plasma levels of HMG-CoA reductase inhibitory activity can increase the risk of myopathy and rhabdomyolysis, particularly with higher doses of lovastatin. The use of lovastatin concomitantly with the potent CYP3A4 inhibitors itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone, or large quantities of grapefruit juice (>1 quart daily) should be avoided. Concomitant use of other medicines labeled as having a potent inhibitory effect on CYP3A4 should be avoided unless the benefits of combined therapy outweigh the increased risk. If treatment with itraconazole, ketoconazole, erythromycin, clarithromycin or telithromycin is unavoidable, therapy with lovastatin should be suspended during the course of treatment. Gemfibrozil, particularly with higher doses of lovastatin: The dose of lovastatin should not exceed 20 mg daily in patients receiving concomitant medication with gemfibrozil. The combined use of lovastatin with gemfibrozil should be avoided, unless the benefits are likely to outweigh the increased risks of this drug combination. Other lipid-lowering drugs (other fibrates or���1 g/day of niacin): The dose of lovastatin should not exceed 20 mg daily in patients receiving concomitant medication with other fibrates or���1 g/day of niacin. Caution should be used when prescribing other fibrates or lipid-lowering doses (���1 g/day) of niacin with lovastatin, as these agents can cause myopathy when given alone. The benefit of further alterations in lipid levels by the combined use of lovastatin with other fibrates or niacin should be carefully weighed against the potential risks of these combinations. Cyclosporine or danazol, with higher doses of lovastatin: The dose of lovastatin should not exceed 20 mg daily in patients receiving concomitant medication with cyclosporine or danazol. The benefits of the use of lovastatin in patients receiving cyclosporine or danazol should be carefully weighed against the risks of these combinations. Amiodarone or verapamil: The dose of lovastatin should not exceed 40 mg daily in patients receiving concomitant medication with amiodarone or verapamil. The combined use of lovastatin at doses higher than 40 mg daily with amiodarone or verapamil should be avoided unless the clinical benefit is likely to outweigh the increased risk of myopathy. The risk of myopathy/rhabdomyolysis is increased when either amiodarone or verapamil is used concomitantly with higher doses of a closely related member of the HMG-CoA reductase inhibitor class. Prescribing recommendations for interacting agents are summarized in TABLE VI (see also CLINICAL PHARMACOLOGY, Pharmacokinetics; PRECAUTIONS, Drug Interactions; DOSAGE AND ADMINISTRATION).<br/>Liver Dysfunction: Persistent increases (to more than 3 times the upper limit of normal) in serum transaminases occurred in 1.9% of adult patients who received lovastatin for at least one year in early clinical trials (see ADVERSE REACTIONS). When the drug was interrupted or discontinued in these patients, the transaminase levels usually fell slowly to pretreatment levels. The increases usually appeared 3 to 12 months after the start of therapy with lovastatin, and were not associated with jaundice or other clinical signs or symptoms. There was no evidence of hypersensitivity. In the EXCEL study (see CLINICAL PHARMACOLOGY, Clinical Studies in Adults), the incidence of persistent increases in serum transaminases over 48 weeks was 0.1% for placebo, 0.1% at 20 mg/day, 0.9% at 40 mg/day, and 1.5% at 80 mg/day in patients on lovastatin. However, in postmarketing experience with lovastatin, symptomatic liver disease has been reported rarely at all dosages (see ADVERSE REACTIONS). In AFCAPS/TexCAPS, the number of participants with consecutive elevations of either alanine aminotransferase (ALT) or aspartate aminotransferase (AST) (>3 times the upper limit of normal), over a median of 5.1 years of follow-up, was not significantly different between the lovastatin and placebo groups (18 [0.6%] vs. 11 [0.3%]). The starting dose of lovastatin was 20 mg/day; 50% of the lovastatin treated participants were titrated to 40 mg/day at Week 18. Of the 18 participants on lovastatin with consecutive elevations of either ALT or AST, 11 (0.7%) elevations occurred in participants taking 20 mg/day, while 7 (0.4%) elevations occurred in participants titrated to 40 mg/day. Elevated transaminases resulted in discontinuation of 6 (0.2%) participants from therapy in the lovastatin group (n = 3,304) and 4 (0.1%) in the placebo group (n = 3,301). It is recommended that liver function tests be performed prior to initiation of therapy in patients with a history of liver disease, or when otherwise clinically indicated. It is recommended that liver function tests be performed in all patients prior to use of 40 mg or more daily and thereafter when clinically indicated. Patients who develop increased transaminase levels should be monitored with a second liver function evaluation to confirm the finding and be followed thereafter with frequent liver function tests until the abnormality(ies) returns to normal. Should an increase in AST or ALT of three times the upper limit of normal or greater persist, withdrawal of therapy with lovastatin is recommended. The drug should be used with caution in patients who consume substantial quantities of alcohol and/or have a past history of liver disease. Active liver disease or unexplained transaminase elevations are contraindications to the use of lovastatin. As with other lipid-lowering agents, moderate (less than three times the upper limit of normal) elevations of serum transaminases have been reported following therapy with lovastatin (see ADVERSE REACTIONS). These changes appeared soon after initiation of therapy with lovastatin, were often transient, were not accompanied by any symptoms, and interruption of treatment was not required.
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| dailymed-drugs:204 |
NOT FOR INJECTION INTO THE EYE. Prolonged use of corticosteroids may result in ocular hypertension/glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision, and in posterior subcapsular cataract formation. Acute anterior uveitis may occur in susceptible individuals, primarily Blacks. Prolonged use of BLEPHAMIDE ophthalmic suspension may suppress the host response and thus increase the hazard of secondary ocular infections. In those diseases causing thinning of the cornea or sclera, perforation has been known to occur with the use of topical corticosteroids. In acute purulent conditions of the eye, corticosteroids may mask infection or enhance existing infection. If the product is used for 10 days or longer, intraocular pressure should be routinely monitored even though it may be difficult in children and uncooperative patients. Corticosteroids should be used with caution in the presence of glaucoma. Intraocular pressure should be checked frequently. A significant percentage of staphylococcal isolates are completely resistant to sulfonamides. The use of steroids after cataract surgery may delay healing and increase the incidence of filtering blebs. The use of ocular corticosteroids may prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex). Employment of corticosteroid medication in the treatment of herpes simplex requires great caution. Topical steroids are not effective in mustard gas keratitis and Sj��gren's keratoconjunctivitis. Fatalities have occurred, although rarely, due to severe reactions to sulfonamides including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia and other blood dyscrasias. Sensitization may recur when a sulfonamide is readministered, irrespective of the route of administration. If signs of hypersensitivity or other serious reactions occur, discontinue use of this preparation. Cross-sensitivity among corticosteroids has been demonstrated .
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| dailymed-drugs:205 |
Anaphylactoid and Possibly Related Reactions:<br/>Head and Neck Angioedema:<br/>Intestinal Angioedema:<br/>Anaphylactoid Reactions During Desensitization:<br/>Anaphylactoid Reactions During Membrane Exposure:<br/>Hypotension:<br/>Leukopenia/Neutropenia/Agranulocytosis:<br/>Hepatic Failure:<br/>Fetal/Neonatal Morbidity and Mortality:
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| dailymed-drugs:206 |
NOT FOR INJECTION. VIGAMOX' solution should not be injected subconjunctivally, nor should it be introduced directly into the anterior chamber of the eye. In patients receiving systemically administered quinolones, including moxifloxacin, serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported, some following the first dose. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema (including laryngeal, pharyngeal or facial edema), airway obstruction, dyspnea, urticaria, and itching. If an allergic reaction to moxifloxacin occurs, discontinue use of the drug. Serious acute hypersensitivity reactions may require immediate emergency treatment. Oxygen and airway management should be administered as clinically indicated.
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| dailymed-drugs:207 |
Amiodarone is intended for use only in patients with the indicated life-threatening arrhythmias because its use is accompanied by substantial toxicity. Amiodarone has several potentially fatal toxicities, the most important of which is pulmonary toxicity (hypersensitivity pneumonitis or interstitial/alveolar pneumonitis) that has resulted in clinically manifest disease at rates as high as 10 to 17% in some series of patients with ventricular arrhythmias given doses around 400 mg/day, and as abnormal diffusion capacitywithout symptoms in a much higher percentage of patients. Pulmonary toxicity has been fatal about 10% of the time. Liver injury is common with amiodarone, but is usually mild and evidenced only by abnormal liver enzymes. Overt liver disease can occur, however, and has been fatal in a few cases. Like other antiarrhythmics, amiodarone can exacerbate the arrhythmia, e.g., by making the arrhythmia less well tolerated or more difficult to reverse. This has occurred in 2 to 5% of patients in various series, andsignificant heart block or sinus bradycardia has been seen in 2 to 5%. All of these events should be manageable in the proper clinical setting in most cases. Although the frequency of such proarrhythmic events does not appear greater with amiodarone than with many other agents used in this population, the effects are prolonged when they occur. Even in patients at high risk of arrhythmic death, in whom the toxicity of amiodarone is an acceptable risk, amiodarone poses major management problems that could be life-threatening in a population at risk of sudden death, so that every effort should be made to utilize alternative agents first. The difficulty of using amiodarone effectively and safely itself poses a significant risk to patients. Patients with the indicated arrhythmias must be hospitalized while the loading dose of amiodarone is given, and a response generally requires at least one week, usually two or more. Because absorption and elimination are variable, maintenance-dose selection is difficult, and it is not unusual to require dosage decrease or discontinuation of treatment. In a retrospective survey of 192 patients with ventricular tachyarrhythmias, 84 required dose reduction and 18 required at least temporary discontinuation because of adverse effects, and several series have reported 15 to 20% overall frequencies of discontinuation due to adverse reactions. The timeat which a previously controlled life-threatening arrhythmia will recur after discontinuation or dose adjustment is unpredictable, ranging from weeks to months. The patient is obviously at great risk during this time and may need prolonged hospitalization. Attempts to substitute other antiarrhythmic agents when amiodarone must be stopped will be made difficult by the gradually, but unpredictably, changing amiodarone body burden. A similar problem exists when amiodarone is not effective; it still poses therisk of an interaction with whatever subsequent treatment is tried.<br/>Mortality: In the National Heart, Lung and Blood Institute's Cardiac Arrhythmia Suppression Trial (CAST), a long-term, multi-centered, randomized, double-blind study in patients with asymptomatic non-life-threatening ventricular arrhythmias who had had myocardial infarctions more than six days but less than two years previously, an excessive mortality or non-fatal cardiac arrest rate was seen in patients treated with encainide or flecainide (56/730) compared with that seen in patients assigned to matched placebo-treated groups (22/725). The average duration of treatment with encainide or flecainide in this study was ten months. Amiodarone therapy was evaluated in two multi-centered, randomized, double-blind, placebo-controlled trials involving 1202 (Canadian Amiodarone Myocardial Infarction Arrhythmia Trial; CAMIAT) and 1486 (European Myocardial Infarction Amiodarone Trial; EMIAT) post-MI patients followed for up to 2 years. Patients in CAMIAT qualified with ventricular arrhythmias, and those randomized to amiodarone received weight- and response-adjusted doses of 200 to 400 mg/day. Patients in EMIAT qualified with ejection fraction<40%, and those randomized to amiodarone received fixed doses of 200 mg/day. Both studies had weeks-long loading dose schedules. Intent-to-treat all-cause mortality results were as follows: These data are consistent with the results of a pooled analysis of smaller, controlled studies involving patients with structural heart disease (including myocardial infarction).<br/>Pulmonary Toxicity: There have been postmarketing reports of acute-onset (days to weeks) pulmonary injury in patients treated with oral amiodarone with or without initial I.V. therapy. Findings have included pulmonary infiltrates and/or mass on X-ray, pulmonary alveolar hemorrhage, bronchospasm, wheezing, fever, dyspnea, cough, hemoptysis, and hypoxia. Some cases have progressed to respiratory failure and/or death. Amiodarone hydrochloride tablets may cause a clinical syndrome of cough and progressive dyspnea accompanied by functional, radiographic, gallium-scan, and pathological data consistent with pulmonary toxicity, the frequency of which varies from 2 to 7% in most published reports, but is as high as 10 to 17% in some reports. Therefore, when amiodarone therapy is initiated, a baseline chest X-ray and pulmonary-function tests, including diffusion capacity, should be performed. The patient should return for a history, physical exam, and chest X-ray every 3 to 6 months. Pulmonary toxicity secondary to amiodarone seems to result from either indirect or direct toxicity as represented by hypersensitivity pneumonitis or interstitial/alveolar pneumonitis, respectively. Patients with preexisting pulmonary disease have a poorer prognosis if pulmonary toxicity develops. Hypersensitivity pneumonitis usually appears earlier in the course of therapy, and rechallenging these patients with amiodarone results in a more rapid recurrence of greater severity. Bronchoalveolar lavage is the procedure of choice to confirm this diagnosis, which can be made when a T suppressor/cytotoxic (CD8-positive) lymphocytosis is noted. Steroid therapy should be instituted and amiodarone therapy discontinued in these patients. Interstitial/alveolar pneumonitis may result from the release of oxygen radicals and/or phospholipidosis and is characterized by findings of diffuse alveolar damage, interstitial pneumonitis or fibrosis in lung biopsy specimens. Phospholipidosis (foamy cells, foamy macrophages), due to inhibition of phospholipase, will be present in most cases of amiodarone-induced pulmonary toxicity; however, these changes also are present in approximately 50% of all patients on amiodarone therapy. These cells should be used as markers of therapy, but not as evidence of toxicity. A diagnosis of amiodarone-induced interstitial/alveolar pneumonitis should lead, at a minimum, to dose reduction or, preferably, to withdrawal of the amiodarone to establish reversibility, especially if other acceptable antiarrhythmic therapies are available. Where these measures have been instituted, a reduction in symptoms of amiodarone-induced pulmonary toxicity was usually noted within the first week, and a clinical improvement was greatest in the first two to three weeks. Chest X-ray changes usually resolve within two to four months. According to some experts, steroids may prove beneficial. Prednisone in doses of 40 to 60 mg/day or equivalent doses of other steroids have been given and tapered over the course of several weeks depending upon the condition of the patient. In some cases rechallenge with amiodarone at a lower dose has not resulted in return of toxicity. Reports suggest that the use of lower loading and maintenance doses of amiodarone are associated with a decreased incidence of amiodarone-induced pulmonary toxicity. In a patient receiving amiodarone, any new respiratory symptoms should suggest the possibility of pulmonary toxicity, and the history, physical exam, chest X-ray, and pulmonary-function tests (with diffusion capacity) should be repeated and evaluated. A 15% decrease in diffusion capacity has a high sensitivity but only a moderate specificity for pulmonary toxicity; as the decrease in diffusion capacity approaches 30%, the sensitivity decreases but the specificity increases. A gallium-scan also may be performed as part of the diagnostic workup. Fatalities, secondary to pulmonary toxicity, have occurred in approximately 10% of cases. However, in patients with life-threatening arrhythmias, discontinuation of amiodarone therapy due to suspected drug-induced pulmonary toxicity should be undertaken with caution, as the most common cause of death in these patients is sudden cardiac death. Therefore, every effort should bemade to rule out other causes of respiratory impairment (i.e., congestive heart failure with Swan-Ganz catheterization if necessary, respiratory infection, pulmonary embolism, malignancy, etc.) before discontinuing amiodarone in these patients. In addition, bronchoalveolar lavage, transbronchial lung biopsy and/or open lung biopsy may be necessary to confirm the diagnosis, especially in those cases where no acceptable alternative therapy is available. If a diagnosis of amiodarone-induced hypersensitivity pneumonitis is made, amiodarone should be discontinued, and treatment with steroids should be instituted. If a diagnosis of amiodarone-induced interstitial/alveolar pneumonitis is made, steroid therapy should be instituted and, preferably, amiodarone discontinued or, at a minimum, reduced in dosage. Some cases of amiodarone-induced interstitial/alveolar pneumonitis may resolve following a reduction in amiodarone dosage in conjunction with the administration of steroids. In some patients, rechallenge at a lower dose has not resulted in return of interstitial/alveolar pneumonitis; however, in some patients (perhaps because of severe alveolar damage) the pulmonary lesions have not been reversible.<br/>Worsened Arrhythmia: Amiodarone, like other antiarrhythmics, can cause serious exacerbation of the presenting arrhythmia, a risk that may be enhanced by the presence of concomitant antiarrhythmics. Exacerbation has been reported in about 2 to 5% in most series, and has included new ventricular fibrillation, incessant ventricular tachycardia, increased resistance to cardioversion, and polymorphicventricular tachycardia associated with QTprolongation (torsade de pointes [TdP]). In addition, amiodarone has caused symptomatic bradycardia or sinus arrest with suppression of escape foci in 2 to 4% of patients. Fluoroquinolones, macrolide antibiotics, and azoles are known to cause QTprolongation. There have been reports of QTprolongation, with or without TdP, in patients taking amiodarone when fluoroquinolones, macrolide antibiotics, or azoles were administered concomitantly. (See Drug Interactions, Other reported interactions with amiodarone.) The need to coadminister amiodarone with any other drug known to prolong the QTinterval must be based on a careful assessment of the potential risks and benefits of doing so for each patient. A careful assessment of the potential risks and benefits of administering amiodarone must be made in patients with thyroid dysfunction due to the possibility of arrhythmia breakthrough or exacerbation of arrhythmia in these patients.<br/>Thyrotoxicosis: Amiodarone-induced hyperthyroidism may result in thyrotoxicosis and/or the possibility of arrhythmia breakthrough or aggravation. There have been reports of death associated with amiodarone-induced thyrotoxicosis. IF ANY NEW SIGNS OF ARRHYTHMIA APPEAR, THE POSSIBILITY OF HYPERTHYROIDISM SHOULD BE CONSIDERED (see PRECAUTIONS, Thyroid Abnormalities).<br/>Liver Injury: Elevations of hepatic enzyme levels are seen frequently in patients exposed to amiodarone and in most cases are asymptomatic. If the increase exceeds three times normal, or doubles in a patient with an elevated baseline, discontinuation of amiodarone or dosage reduction should be considered. In a few cases in which biopsy has been done, the histology has resembled that of alcoholic hepatitis or cirrhosis. Hepatic failure has been a rare cause of death in patients treated with amiodarone.<br/>Loss of Vision: Cases of optic neuropathy and/or optic neuritis, usually resulting in visual impairment, have been reported in patients treated with amiodarone. In some cases, visual impairment has progressed to permanent blindness. Optic neuropathy and/or neuritis may occur at any time following initiation of therapy. A causal relationship to the drug has not been clearly established. If symptoms of visual impairment appear, such as changes in visual acuity and decreases in peripheral vision, prompt ophthalmic examination is recommended. Appearance of optic neuropathy and/or neuritis calls for re-evaluation of amiodarone therapy. The risks and complications of antiarrhythmic therapy with amiodarone must be weighed against its benefits in patients whose lives are threatened by cardiac arrhythmias. Regular ophthalmic examination, including fundoscopy and slit-lamp examination, is recommended during administration of amiodarone. (See ADVERSE REACTIONS.)<br/>Neonatal Hypo- or Hyperthyroidism: Amiodarone can cause fetal harm when administered to a pregnant woman. Although amiodarone use during pregnancy is uncommon, there have been a small number of published reports of congenital goiter/hypothyroidism and hyperthyroidism. If amiodarone is used during pregnancy, or if the patient becomes pregnant while taking amiodarone, the patient should be apprised of the potential hazard to the fetus. In general, amiodarone hydrochloride tablets should be used during pregnancy only if the potential benefit to the mother justifies the unknown risk to the fetus. In pregnant rats and rabbits, amiodarone hydrochloride in doses of 25 mg/kg/day (approximately 0.4 and 0.9 times, respectively, the maximum recommended human maintenance dose) had no adverse effects on the fetus. In the rabbit, 75 mg/kg/day (approximately 2.7 times the maximum recommended human maintenance dose) caused abortions in greater than 90% of the animals. In the rat, doses of 50 mg/kg/day or more were associated with slight displacement of the testes and an increased incidence of incomplete ossification of some skull and digital bones; at 100 mg/kg/day or more, fetal body weights were reduced; at 200 mg/kg/day, there was an increased incidence of fetal resorption. (These doses in the rat are approximately 0.8, 1.6 and 3.2 times the maximum recommended human maintenance dose.) Adverse effects on fetal growth and survival also were noted in one of two strains of mice at a dose of 5 mg/kg/day (approximately 0.04 times the maximum recommended human maintenance dose).
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| dailymed-drugs:209 |
Particular care is needed in patients who are transferred from systemically active corticosteroids to AEROSPAN Inhalation Aerosol because deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids. After withdrawal from systemic corticosteroids, a number of months are required for recovery of hypothalamic-pituitary-adrenal (HPA) function. Patients who have been previously maintained on 20 mg or more per day of prednisone (or its equivalent) may be most susceptible, particularly when their systemic corticosteroids have been almost completely withdrawn. During this period of HPA suppression, patients may exhibit signs and symptoms of adrenal insufficiency when exposed to trauma, surgery or infections (particularly gastroenteritis) or other conditions associated with severe electrolyte loss. Although AEROSPAN Inhalation Aerosol may provide control of asthmatic symptoms during these episodes, in recommended doses it supplies less than the physiologic amounts of glucocorticoid systemically and does NOT provide the mineralocorticoid activity that is necessary for coping with these emergencies. During periods of stress or a severe asthmatic attack, patients who have been withdrawn from systemic corticosteroids should be instructed to resume systemic steroids (in large doses) immediately and to contact their physician for further instruction. These patients should also be instructed to carry a warning card indicating that they may need supplementary systemic steroids during periods of stress or a severe asthma attack. Patients requiring oral corticosteroids should be weaned slowly from systemic corticosteroid use after transferring to AEROSPAN Inhalation Aerosol. Lung function (FEVor AM PEF), beta-agonist use, and asthma symptoms should be carefully monitored during withdrawal of oral corticosteroids. In addition to monitoring asthma signs and symptoms, patients should be observed for signs and symptoms of adrenal insufficiency such as fatigue, lassitude, weakness, nausea and vomiting, and hypotension. Transfer of patients from systemic corticosteroid therapy to AEROSPAN Inhalation Aerosol may unmask allergic conditions previously suppressed by the systemic corticosteroid therapy, e.g. rhinitis, conjunctivitis, eczema, arthritis, and eosinophilic conditions. Patients who are on drugs that suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in non-immune children or adults on corticosteroids. In such children or adults who have not had these diseases or been properly immunized, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affects the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If exposed to chickenpox, prophylaxis with varicella-zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If chickenpox develops, treatment with antiviral agents may be considered. AEROSPAN Inhalation Aerosol is not a bronchodilator and is not indicated for rapid relief of bronchospasm. As with other inhaled asthma medications, bronchospasm may occur with an immediate increase in wheezing after dosing. If bronchospasm occurs following dosing with AEROSPAN Inhalation Aerosol, it should be treated immediately with a fast-acting inhaled bronchodilator. Treatment with AEROSPAN Inhalation Aerosol should be discontinued and alternative therapy instituted. Patients should be instructed to contact their physician immediately when episodes of asthma that are not responsive to bronchodilators occur during the course of treatment with AEROSPAN Inhalation Aerosol. During such episodes, patients may require therapy with systemic corticosteroids.
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| dailymed-drugs:211 |
Cardiac Failure: Sympathetic stimulation is necessary in supporting circulatory function in congestive heart failure, and beta blockade carries the potential hazard of further depressing myocardial contractility and precipitating more severe failure. In patients who have congestive heart failure controlled by digitalis and/or diuretics, TENORETIC should be administered cautiously. Both digitalis and atenolol slow AV conduction. IN PATIENTS WITHOUT A HISTORY OF CARDIAC FAILURE, continued depression of the myocardium with beta-blocking agents over a period of time can, in some cases, lead to cardiac failure. At the first sign or symptom of impending cardiac failure, patients should be treated appropriately according to currently recommended guidelines, and the response observed closely. If cardiac failure continues despite adequate treatment, TENORETIC should be withdrawn.<br/>Renal and Hepatic Disease and Electrolyte Disturbances: Since atenolol is excreted via the kidneys, TENORETIC should be used with caution in patients with impaired renal function. In patients with renal disease, thiazides may precipitate azotemia. Since cumulative effects may develop in the presence of impaired renal function, if progressive renal impairment becomes evident, TENORETIC should be discontinued. In patients with impaired hepatic function or progressive liver disease, minor alterations in fluid and electrolyte balance may precipitate hepatic coma. TENORETIC should be used with caution in these patients.<br/>Ischemic Heart Disease: Following abrupt cessation of therapy with certain beta-blocking agents in patients with coronary artery disease, exacerbations of angina pectoris and, in some cases, myocardial infarction have been reported. Therefore, such patients should be cautioned against interruption of therapy without the physician's advice. Even in the absence of overt angina pectoris, when discontinuation of TENORETIC is planned, the patient should be carefullyobserved and should be advised to limit physical activity to a minimum. TENORETIC should be reinstated if withdrawal symptoms occur. Because coronary artery disease is common and may be unrecognized, it may be prudent not to discontinue TENORETIC therapy abruptly even in patients treated only for hypertension.<br/>Concomitant Use of Calcium Channel Blockers: Bradycardia and heart block can occur and the left ventricular end diastolic pressure can rise when beta-blockers are administered with verapamil or diltiazem. Patients with pre-existing conduction abnormalities or left ventricular dysfunction are particularly susceptible.<br/>Bronchospastic Diseases: PATIENTS WITH BRONCHOSPASTIC DISEASE SHOULD, IN GENERAL, NOT RECEIVE BETA BLOCKERS. Because of its relative beta-selectivity, however, TENORETIC may be used with caution in patients with bronchospastic disease who do not respond to or cannot tolerate, other antihypertensive treatment. Since beta-selectivity is not absolute, the lowest possible dose of TENORETIC should be used and a beta-stimulating agent (bronchodilator) should be made available. If dosage must be increased, dividing the dose should be considered in order to achieve lower peak blood levels.<br/>Anesthesia and Major Surgery: It is not advisable to withdraw beta-adrenoreceptor blocking drugs prior to surgery in the majority of patients. However, care should be taken when using anesthetic agents such as those which may depress the myocardium. Vagal dominance, if it occurs, may be corrected with atropine (1-2 mg IV). Beta blockers are competitive inhibitors of beta-receptor agonists and their effects on the heart can be reversed by administration of such agents; eg, dobutamine or isoproterenol with caution .<br/>Metabolic and Endocrine Effects: TENORETIC may be used with caution in diabetic patients. Beta blockers may mask tachycardia occurring with hypoglycemia, but other manifestations such as dizziness and sweating may not be significantly affected. At recommended doses atenolol does not potentiate insulin-induced hypoglycemia and, unlike nonselective beta blockers, does not delay recovery of blood glucose to normal levels. Insulin requirements in diabetic patients may be increased, decreased or unchanged; latent diabetes mellitus may become manifest during chlorthalidone administration. Beta-adrenergic blockade may mask certain clinical signs (eg, tachycardia) of hyperthyroidism. Abrupt withdrawal of beta blockade might precipitate a thyroid storm; therefore, patients suspected of developing thyrotoxicosis from whom TENORETIC therapy is to be withdrawn should be monitored closely. Because calcium excretion is decreased by thiazides, TENORETIC should be discontinued before carrying out tests for parathyroid function. Pathologic changes in the parathyroid glands, with hypercalcemia and hypophosphatemia, have been observed in a few patients on prolonged thiazide therapy; however, the common complications of hyperparathyroidism such as renal lithiasis, bone resorption, and peptic ulceration have not been seen. Hyperuricemia may occur, or acute gout may be precipitated in certain patients receiving thiazide therapy.<br/>Untreated Pheochromocytoma: TENORETIC should not be given to patients with untreated pheochromocytoma.
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| dailymed-drugs:212 |
Deaths have been reported in children less than 2 years of age who were taking antihistamines, including carbinoxamine-containing drug products, therefore, carbinoxamine maleate is contraindicated in children younger than 2 years of age . Antihistamines should be used with considerable caution in patients with: narrow angle glaucoma, stenosing peptic ulcer, symptomatic prostatic hypertrophy, bladder neck obstruction, pyloroduodenal obstruction.
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| dailymed-drugs:213 |
FOR OTIC USE ONLY(This product is not approved for ophthalmic use.) NOT FOR INJECTIONCIPRODEX' Otic should be discontinued at the first appearance of a skin rash or any other sign of hypersensitivity. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions, some following the first dose, have been reported in patients receiving systemic quinolones. Serious acute hypersensitivity reactions may require immediate emergency treatment.
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| dailymed-drugs:214 |
Patient experience with trientine hydrochloride is limited . Patients receiving SYPRINE should remain under regular medical supervision throughout the period of drug administration. Patients (especially women) should be closely monitored for evidence of iron deficiency anemia.
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| dailymed-drugs:216 |
A theoretical hazard may exist for patients being treated with lactulose solution who may be required to undergo electrocautery procedures during proctoscopy or colonoscopy. Accumulation of Hgas in significant concentration in the presence of an electrical spark may result in an explosive reaction. Although this complication has not been reported with lactulose, patients on lactulose therapy undergoing such procedures should have a thorough bowel cleansing with a non-fermentable solution. Insufflation of COas an additional safeguard may be pursued but is considered to be a redundant measure.
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| dailymed-drugs:1591 |
A theoretical hazard may exist for patients being treated with lactulose solution who may be required to undergo electrocautery procedures during proctoscopy or colonoscopy. Accumulation of Hgas in significant concentration in the presence of an electrical spark may result in an explosive reaction. Although this complication has not been reported with lactulose, patients on lactulose therapy undergoing such procedures should have a thorough bowel cleansing with a non-fermentable solution. Insufflation of COas an additional safeguard may be pursued but is considered to be a redundant measure.
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| dailymed-drugs:2797 |
A theoretical hazard may exist for patients being treated with lactulose solution who may be required to undergo electrocautery procedures during proctoscopy or colonoscopy. Accumulation of Hgas in significant concentration in the presence of an electrical spark may result in an explosive reaction. Although this complication has not been reported with lactulose, patients on lactulose therapy undergoing such procedures should have a thorough bowel cleansing with a non-fermentable solution. Insufflation of COas an additional safeguard may be pursued but is considered to be a redundant measure.
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| dailymed-drugs:2835 |
A theoretical hazard may exist for patients being treated with lactulose solution who may be required to undergo electrocautery procedures during proctoscopy or colonoscopy. Accumulation of Hgas in significant concentration in the presence of an electrical spark may result in an explosive reaction. Although this complication has not been reported with lactulose, patients on lactulose therapy undergoing such procedures should have a thorough bowel cleansing with a non-fermentable solution. Insufflation of COas an additional safeguard may be pursued but is considered to be a redundant measure.
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| dailymed-drugs:2914 |
A theoretical hazard may exist for patients being treated with lactulose solution who may be required to undergo electrocautery procedures during proctoscopy or colonoscopy. Accumulation of Hgas in significant concentration in the presence of an electrical spark may result in an explosive reaction. Although this complication has not been reported with lactulose, patients on lactulose therapy undergoing such procedures should have a thorough bowel cleansing with a non-fermentable solution. Insufflation of COas an additional safeguard may be pursued but is considered to be a redundant measure.
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| dailymed-drugs:2997 |
A theoretical hazard may exist for patients being treated with lactulose solution who may be required to undergo electrocautery procedures during proctoscopy or colonoscopy. Accumulation of Hgas in significant concentration in the presence of an electrical spark may result in an explosive reaction. Although this complication has not been reported with lactulose, patients on lactulose therapy undergoing such procedures should have a thorough bowel cleansing with a non-fermentable solution. Insufflation of COas an additional safeguard may be pursued but is considered to be a redundant measure.
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| dailymed-drugs:3256 |
A theoretical hazard may exist for patients being treated with lactulose solution who may be required to undergo electrocautery procedures during proctoscopy or colonoscopy. Accumulation of Hgas in significant concentration in the presence of an electrical spark may result in an explosive reaction. Although this complication has not been reported with lactulose, patients on lactulose therapy undergoing such procedures should have a thorough bowel cleansing with a non-fermentable solution. Insufflation of COas an additional safeguard may be pursued but is considered to be a redundant measure.
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| dailymed-drugs:217 |
Patients under therapy with MAO inhibitors may experience a severe hypertensive crisis if given a sympathomimetic drug. Use in children, especially infants, may result in CNS depression leading to coma and marked reduction in body temperature.
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| dailymed-drugs:219 |
RIBASPHERE (ribavirin, USP) must not be used alone because ribavirin monotherapy is not effective for the treatment of chronic hepatitis C virus infection. The safety and efficacy of
ribavirin have only been established when used together with
peginterferon alfa-2a, recombinant. RIBASPHERE (ribavirin, USP) and peginterferon alfa-2a should be discontinued in patients who develop evidence of hepatic decompensation during treatment. There are significant adverse events caused by
ribavirin/peginterferon alfa-2a therapy, including severe depression and suicidal ideation, hemolytic anemia, suppression of bone marrow function, autoimmune and infectious disorders, pulmonary dysfunction, pancreatitis, and diabetes. The
PEGASYS package insert and MEDICATION GUIDE should be reviewed in their entirety prior to initiation of combination treatment for additional safety information.<br/>General: Treatment with RIBASPHERE (ribavirin, USP) and peginterferon alfa-2a should be administered under the guidance of a qualified physician and may lead to moderate to severe adverse experiences requiring dose reduction, temporary dose cessation or discontinuation of therapy.<br/>Pregnancy: Ribavirin may cause birth defects and/or death of the exposed fetus. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin has demonstrated significant teratogenic and/or embryocidal effects in all animal species in which adequate studies have been conducted. These effects occurred at doses as low as one twentieth of the recommended human dose of ribavirin.
RIBASPHERE (ribavirin, USP) THERAPY SHOULD NOT BE STARTED UNLESS A REPORT OF A NEGATIVE PREGNANCY TEST HAS BEEN OBTAINED IMMEDIATELY PRIOR TO PLANNED INITIATION OF THERAPY. Patients should be instructed to use at least two forms of effective contraception during treatment and for 6 months after treatment has been stopped. Pregnancy testing should occur monthly during
RIBASPHERE (ribavirin, USP) therapy and for 6 months after therapy has stopped .<br/>Anemia: The primary toxicity of ribavirin is hemolytic anemia (hemoglobin<10 g/dL), which was observed in approximately 13% of all
ribavirin and
peginterferon alfa-2a treated patients in clinical trials . The anemia associated with
ribavirin occurs within 1 to 2 weeks of initiation of therapy. BECAUSE THE INITIAL DROP IN HEMOGLOBIN MAY BE SIGNIFICANT, IT IS ADVISED THAT HEMOGLOBIN OR HEMATOCRIT BE OBTAINED PRETREATMENT AND AT WEEK 2 AND WEEK 4 OF THERAPY OR MORE FREQUENTLY IF CLINICALLY INDICATED. Patients should then be followed asclinically appropriate. Fatal and nonfatal myocardial infarctions have been reported in patients with anemia caused by ribavirin. Patients should be assessed for underlying cardiac disease before initiation of ribavirin therapy. Patients with pre-existing cardiac disease should have electrocardiograms administered before treatment, and should be appropriately monitored during therapy. If there is any deterioration of cardiovascular status, therapy should be suspended or discontinued (see DOSAGE AND ADMINISTRATION: RIBASPHERE (ribavirin, USP) Dosage Modification Guidelines). Because cardiac disease may be worsened by drug induced anemia, patients with a history of significant or unstable cardiac disease should not use
RIBASPHERE (ribavirin, USP) .<br/>Hepatic Failure: Chronic hepatitis C (CHC) patients with cirrhosis may be at risk of hepatic decompensation and death when treated with alpha interferons, including peginterferon alfa-2a. During treatment, patients' clinical status and hepatic function should be closely monitored, and peginterferon alfa-2a treatment should be immediately discontinued if decompensation (Child-Pugh score���6) is observed .<br/>Pulmonary: Pulmonary symptoms, including dyspnea, pulmonary infiltrates, pneumonitis and occasional cases of fatal pneumonia, have been reported during therapy with ribavirin and interferon. In addition, sarcoidosis or the exacerbation of sarcoidosis has been reported. If there is evidence of pulmonary infiltrates or pulmonary function impairment, the patient should be closely monitored and, if appropriate, combination RIBASPHERE (ribavirin, USP)/peginterferon alfa-2a treatment should be discontinued.<br/>Other: RIBASPHERE (ribavirin, USP) and peginterferon alfa-2a therapy should be suspended in patients with signs and symptoms of pancreatitis, and discontinued in patients with confirmed pancreatitis. RIBASPHERE (ribavirin, USP) should not be used in patients with creatinine clearance<50 mL/min . RIBASPHERE (ribavirin, USP) must be discontinued immediately and appropriate medical therapy instituted if an acute hypersensitivity reaction (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) develops. Transient rashes do not necessitate interruption of treatment.
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| dailymed-drugs:220 |
CARDIOVASCULAR EFFECTS Cardiovascular Thrombotic Events Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the signs and/or symptoms of serious CV events and the steps to take if they occur. There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID does increase the risk of serious GI events (see GI WARNINGS). Two large, controlled, clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke (see CONTRAINDICATIONS). Hypertension NSAIDs, including oxaprozin, can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including oxaprozin, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy. Congestive Heart Failure and Edema Fluid retention and edema have been observed in some patients taking NSAIDs. Oxaprozin should be used with caution in patients with fluid retention or heart failure. Gastrointestinal Effects-Risk of Ulceration, Bleeding and Perforation NSAIDs, including oxaprozin, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients, who develop a serious upper GI adverse event on NSAID therapy, is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3-6 months, and in about 2-4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk. NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding who use NSAIDs have a greater than 10-fold increased risk for developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore, special care should be taken in treating this population. To minimize the potential risk for an adverse GI event in patients treated with an NSAID, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high risk patients, alternate therapies that do not involve NSAIDs should be considered. Renal Effects Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a nonsteroidal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greater risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state. Advanced Renal Disease No information is available from controlled clinical studies regarding the use of oxaprozin in patients with advanced renal disease. Therefore, treatment with oxaprozin is not recommended in these patients with advanced renal disease. If oxaprozin therapy must be initiated, close monitoring of the patient's renal function is advisable. Anaphylactoid Reactions As with other NSAIDs, anaphylactoid reactions may occur in patients without known prior exposure to oxaprozin. Oxaprozin should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs (see CONTRAINDICATIONS and PRECAUTIONS: Preexisting Asthma). Emergency help should be sought in cases where an anaphylactoid reaction occurs. Skin Reactions NSAIDs, including oxaprozin, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Patients should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity. Pregnancy In late pregnancy, as with other NSAIDs, oxaprozin should be avoided because it may cause premature closure of the ductus arteriosus.
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| dailymed-drugs:221 |
See BOXED WARNINGS.<br/>1. Cardiovascular disorders: Estrogen-plus-progestin therapy has been associated with an increased risk of myocardial infarction as well as stroke, venous thrombosis and pulmonary embolism. Estrogen-alone therapy has been associated with an increased risk of stroke and deep vein thrombosis (DVT). Should any of these events occur or be suspected, estrogens should be discontinued immediately. Risk factors for arterial vascular disease (e.g., hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (e.g., personal history or family history of VTE, obesity, and systemic lupus erythematosus) should be managed appropriately.<br/>a. stroke: In the estrogen plus progestin substudy of the Women's Health Initiative (WHI), a statistically significant increased risk of stroke was reported in women receiving CE/MPA 0.625 mg/2.5 mg daily compared to woman receiving placebo (31 vs. 24 per 10,000 women-years). The increase in risk was demonstrated after the first year and persisted. . In the estrogen-alone substudy of the WHI, a statistically significant increased risk of stroke was reported in women receiving CE 0.625 mg daily compared to women receiving placebo (44 vs. 32 per 10,000 women-years). The increase in risk was demonstrated in year one and persisted.<br/>b. coronary heart disease: In the estrogen-plus progestin sub-study of WHI, no statistically significant increase in CHD events (defined as non-fatal, MI, silent MI, or death, due to CHD) was reported in women receiving CE/MPA compared to women receiving placebo (39 vs. 33 per 10,000 women-years). An increase in relative risk was demonstrated in year one, and a trend toward decreasing relative risk was reported in years 2 through 5. In the estrogen-alone substudy of WHI, no overall effect on coronary disease (CHD) events was reported in women receiving estrogen alone compared to placebo. In postmenopausal women with documented heart disease (n=2,763, average age 66.7 years), a controlled clinical trial of secondary prevention of cardiovascular disease (Heart and Estrogen/Progestin Replacement Study (HERS)) treatment with CE/MPA (0.625mg/2.5mg per day) demonstrated no cardiovascular benefit. During an average follow-up of 4.1 years, treatment with CE/MPA did not reduce the overall rate of CHD events in postmenopausal women with established coronary heart disease. There were more CHD events in the CE/MPA-treated group than in the placebo group in year 1, but not during the subsequent years. Participation in an open-label extension ofthe original HERS trial (HERS II) was agreed to by 2,321 women. Average follow-up in HERS II was an additional 2.7 years, for a total of 6.8 years overall. Rates of CHD events were comparable among women in the CE/MPA group and the placebo group in HERS, HERS II, and overall. Large doses of estrogen (5 mg conjugated estrogens per day), comparable to those used to treat cancer of the prostate and breast, have been shown in a large prospective clinical trial in men to increase the risk of nonfatal myocardial infarction, pulmonary embolism, and thrombophlebitis.<br/>c. Venous thromboembolism: In the estrogen-plus-progestin substudy of the Women's Health Initiative (WHI), a statistically significant 2-fold greater rate of VTE (DVT and pulmonary embolism [PE]), was reported in women receiving CE/MPA compared to women receiving placebo (35 vs. 17 per 10,000 women-years). Statistically significant increases in risk for both DVT (26 vs. 13 per 10,000 women-years) and PE (18 vs. 8 per 10,000 women-years) were also demonstrated. The increase in VTE risk was demonstrated during the first year and persisted. In the estrogen-alone substudy of WHI, therisk of VTE was reported to be increased for women taking conjugated estrogens (30 vs. 22 per 10,000 women-years), although only the increased risk of DVT reached statistical significance (23 vs. 15 per 10,000 women-years). The increase in VTE risk was demonstrated during the first two years. If feasible, estrogens should be discontinued at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization.<br/>2. Malignant neoplasms:<br/>a. Breast cancer: In some studies, the use of estrogens and progestins by postmenopausal women has been reported to increase the risk of breast cancer. The most important randomized clinical trial providing information about this issue is the CE/MPA substudy of the WHI study . The results from observational studies are generally consistent with those of the WHI clinical trial. Observational studies have also reported an increased risk of breast cancer for estrogen-plus-progestin combination therapy, and a smaller increased risk for estrogen-alone therapy, after several years of use. For both findings, the excess risk increased with duration of use, and appeared to return to baseline over about five years after stopping treatment (only the observational studies have substantial data on risk after stopping). In these studies, the risk of breast cancer was greater, and became apparent earlier, with estrogen-plus-progestin combination therapy as compared to estrogen-alone therapy. However, these studies have not found significant variation in the risk of breast cancer among different estrogens or among different estrogen-plus-progestin combinations, doses, or routes of administration. In the estrogen-plus-progestin substudy, after a mean follow-up of 5.6 years, the WHI substudy reported an increased risk of breast cancer. In this substudy, prior use of estrogen alone or estrogen-plus-progestin combination hormone therapy was reported by 26% of the women. The relative risk of invasive breast cancer was 1.24 (95% nCI 1.01-1.54), and the absolute risk was 41 vs. 33 cases per 10,000 women-years, for estrogen plus progestin compared with placebo, respectively. Among women who reported prior use of hormone therapy, the relative risk of invasive breast cancer was 1.86, and the absolute risk was 46 vs. 25 cases per 10,000 women-years, for estrogen plus progestin compared with placebo. Among women who reported no prior use of hormone therapy, the relative risk of invasive breast cancer was 1.09, and the absolute risk was 40 vs. 36 cases per 10,000 women-years of estrogen plus progestin compared with placebo. In the WHI trial, invasive breast cancers were larger and diagnosed at a more advanced stage in the estrogen-plus-progestin group compared with the placebo group. Metastatic disease wasrare, with no apparent difference between the two groups. Other prognostic factors, such as histologic subtype, grade and hormone receptor status did not differ between the groups. In the estrogen-alone substudy of WHI, after an average of 7.1 years of follow-up, CE (0.625 mg daily) was not associated with an increased risk of invasive breast cancer (RR 0.80, 95% nCI 0.62-1.04). In a one-year trial among 1,176 women who received either unopposed 1 mg estradiol or a combination of 1 mg estradiol plus one of three different doses of NETA (0.1, 0.25, and 0.5 mg), seven new cases of breast cancer were diagnosed, two of which occurred among the group of 295 women treated with Activella 1.0 mg/0.5 mg and two of which occurred among the group of 294 women treated with 1 mg estradiol/0.1 mg NETA. The use of estrogen alone and estrogen plus progestin has been reported to result in an increase in abnormal mammograms requiring further evaluation. All women should receive yearly breast examinations by a health care provider and perform monthly breast self-examinations. In addition, mammography examinations should be scheduled based on patient age, risk factors, and prior mammogram results.<br/>b. Endometrial cancer: The use of unopposed estrogens in women with intact uteri has been associated with an increased risk of endometrial cancer. The reported endometrial cancer risk among unopposed estrogen users is about 2 to 12 fold greater than in nonusers, and appears dependent on duration of treatment and on estrogen dose. Most studies show no significant increased risk associated with use of estrogens for less than one year. The greatest risk appears associated with prolonged use, with an increased risk of 15- to 24-fold for five to ten years or more. This risk has been shown to persist for at least 8 to 15 years after estrogen therapy is discontinued. Clinical surveillance of all women taking estrogen/progestin combinations is important. Adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding. There is no evidence that the use of natural estrogens results in a different endometrial risk profile than synthetic estrogens of equivalent estrogen dose. Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Endometrial hyperplasia (a possible precursor of endometrial cancer) has been reported to occur in approximately 1% or less with Activella in one large clinical trial.<br/>3. Dementia: In the estrogen-plus-progestin Women's Health Initiative Memory Study (WHIMS), a substudy of WHI, a population of 4,532 postmenopausal women aged 65 to 79 years was randomized to CE/MPA (0.625 mg/2.5 mg daily) or placebo. In the estrogen-alone WHIMS substudy, a population of 2,947 hysterectomized women, aged 65 to 79 years, was randomized to CE (0.625 mg daily) or placebo. In the estrogen-plus-progestin substudy, after an average follow-up of four years, 40 women in the estrogen-plus-progestin group and 21 women in the placebo group were diagnosed with probable dementia. The relative risk of probable dementia for estrogen plus progestin vs. placebo was 2.05 (95% CI 1.21-3.48). The absolute risk of probable dementia for CE/MPA vs. placebo was 45 vs. 22 cases per 10,000 women-years. In the estrogen-alone substudy, after an average follow-up of 5.2 years, 28 women in the estrogen-alone group and 19 women in the placebo group were diagnosed with probable dementia. The relative risk of probable dementia for CE alone vs. placebo was 1.49 (95% CI 0.83-2.66). The absolute risk of probable dementia for CE alone vs. placebo was 37 vs. 25 cases per 10,000 women-years. When data from the two populations were pooled as planned in the WHIMS protocol, the reported overall relative risk of probable dementia was 1.76 (95% CI 1.19-2.60). Since both substudies were conducted in women ages 65 to 79, it is unknown whether these findings apply to younger postmenopausal women.<br/>4. Gallbladder disease: A two-to four fold increase in the risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens has been reported.<br/>5. Hypercalcemia: Estrogen administration may lead to severe hypercalcemia in patients with breast cancer and bone metastases. If hypercalcemia occurs, use of the drug should be stopped and appropriate measures taken to reduce the serum calcium level.<br/>6. Visual abnormalities: Retinal vascular thrombosis has been reported in patients receiving estrogens. Discontinue medication pending examination if there is a sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia, or migraine. If examination reveals papilledema or retinal vascular lesions, estrogens should be permanently discontinued.
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Prolonged use of a topical ocular anesthetic is not recommended. It may produce permanent corneal opacification with accompanying visual loss.
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Anaphylactoid and Possibly Related Reactions: Presumably because angiotensin-converting enzyme inhibitors affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin, patients receiving ACE inhibitors (including ALTACE) may be subject to a variety of adverse reactions, some of them serious.<br/>Head and Neck Angioedema: Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor. Angioedema of the face, extremities, lips, tongue, glottis, and larynx has been reported in patients treated with angiotensin converting enzyme inhibitors. Angioedema associated with laryngeal edema can be fatal. If laryngeal stridor or angioedema of the face, tongue, or glottis occurs, treatment with ALTACE should be discontinued and appropriate therapy instituted immediately. Where there is involvement of the tongue, glottis, or larynx, likely to cause airway obstruction, appropriate therapy, e.g., subcutaneous epinephrine solution 1:1,000 (0.3 ml to 0.5 ml) should be promptly administered.<br/>Intestinal Angioedema: Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain. In a large U.S. postmarketing study, angioedema (defined as reports of angio, face, larynx, tongue, or throat edema) was reported in 3/1523 (0.20%) of black patients and in 8/8680 (0.09%) of white patients. These rates were not different statistically. Anaphylactoid reactions during desensitization: Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions. In the same patients, these reactions were avoided when ACE inhibitors were temporarily withheld, but they reappeared upon inadvertent rechallenge. Anaphylactoid reactions during membrane exposure: Anaphylactoid reactions have been reported in patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption.<br/>Hypotension: ALTACE can cause symptomatic hypotension, after either the initial dose or a later dose when the dosage has been increased. Like other ACE inhibitors, ramipril has been only rarely associated with hypotension in uncomplicated hypertensive patients. Symptomatic hypotension is most likely to occur in patients who have been volume- and/or salt-depleted as a result of prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea, or vomiting. Volume and/or salt depletion should be corrected before initiating therapy with ALTACE. In patients with congestive heart failure, with or without associated renal insufficiency, ACE inhibitor therapy may cause excessive hypotension, which may be associated with oliguria or azotemia and, rarely, with acute renal failure and death. In such patients, ALTACE therapy should be started under close medical supervision; they should be followed closely for the first 2 weeks of treatment and whenever the dose of ramipril or diuretic is increased. If hypotension occurs, the patient should be placed in a supine position and, if necessary, treated with intravenous infusion of physiological saline. ALTACE treatment usually can be continued following restoration of blood pressure and volume.<br/>Hepatic Failure: Rarely, ACE inhibitors, including Altace, have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up.<br/>Neutropenia/Agranulocytosis: As with other ACE inhibitors, rarely, a mild���in isolated cases severe���reduction in the red blood cell count and hemoglobin content, white blood cell or platelet count may develop. In isolated cases, agranulocytosis, pancytopenia, and bone marrow depression may occur. Hematological reactions to ACE inhibitors are more likely to occur in patients with collagen vascular disease (e.g. systemic lupus erythematosus, scleroderma) and renal impairment. Monitoring of white blood cell counts should be considered in patients with collagen-vascular disease, especially if the disease is associated with impaired renal function.<br/>Fetal/Neonatal Morbidity and Mortality: ACE inhibitors can cause fetal and neonatal morbidity and death when administered to pregnant women. Several dozen cases have been reported in the world literature. When pregnancy is detected, ACE inhibitors should be discontinued as soon as possible. The use of ACE inhibitors during the second and third trimesters of pregnancy has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death. Oligohydramnios has also been reported, presumably resulting from decreased fetal renal function; oligohydramnios in this setting has been associated with fetal limb contractures, craniofacial deformation, and hypoplastic lung development. Prematurity, intrauterine growth retardation, and patent ductus arteriosus have also been reported, although it is not clear whether these occurrences were due to the ACE inhibitor exposure. In a published retrospective epidemiological study, infants whose mothers had taken an ACE inhibitor during their first trimester of pregnancy appeared to have an increased risk of major congenital malformations compared with infants whose mothers had not undergone first trimester exposure to ACE inhibitor drugs. The number of cases of birth defects is small and the findings of this study have not yet been confirmed. Rarely (probably less often than once in every thousand pregnancies), no alternative to ACE inhibitors will be found. In these rare cases, the mothers should be apprised of the potential hazards to their fetuses, and serial ultrasound examinations should be performed to assess the intraamniotic environment. If oligohydramnios is observed, ALTACE should be discontinued unless it is considered life-saving for the mother. Contraction stress testing (CST), a non-stress test (NST), or biophysical profiling (BPP) may be appropriate, depending upon the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Infants with histories of in utero exposure to ACE inhibitors should be closely observed for hypotension, oliguria, and hyperkalemia. If oliguria occurs, attention should be directed toward support of blood pressure and renal perfusion. Exchange transfusion or dialysis may be required as means of reversing hypotension and/or substituting for disordered renal function. ALTACE which crosses the placenta can be removed from the neonatal circulation by these means, but limited experience has not shown that such removal is central to the treatment of these infants. No teratogenic effects of ALTACE were seen in studies of pregnant rats, rabbits, and cynomolgus monkeys. On a body surface area basis, the doses used were up to approximately 400 times (in rats and monkeys) and 2 times (in rabbits) the recommended human dose.
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Potassium supplementation, either in the form of medication or as a diet rich in potassium, should not ordinarily be given in association with Aldactone therapy. Excessive potassium intake may cause hyperkalemia in patients receiving Aldactone (see Precautions: General). Aldactone should not be administered concurrently with other potassium-sparing diuretics. Aldactone, when used with ACE inhibitors or indomethacin, even in the presence of a diuretic, has been associated with severe hyperkalemia. Extreme caution should be exercised when Aldactone is given concomitantly with these drugs. Aldactone should be used with caution in patients with impaired hepatic function because minor alterations of fluid and electrolyte balance may precipitate hepatic coma. Lithium generally should not be given with diuretics (see Precautions: Drug interactions).
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SERIOUS AND
OCCASIONALLY FATAL HYPERSENSITIVITY (ANAPHYLACTIC) REACTIONS HAVE BEEN
REPORTED IN PATIENTS ON PENICILLIN THERAPY. THESE REACTIONS ARE MORE APT
TO OCCUR IN INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY
AND/OR HYPERSENSITIVITY REACTIONS TO MULTIPLE ALLERGENS. THERE HAVE BEEN
REPORTS OF INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY WHO
HAVE EXPERIENCED SEVERE REACTIONS WHEN TREATED WITH CEPHALOSPORINS.
BEFORE THERAPY WITH A PENICILLIN, CAREFUL INQUIRY SHOULD BE MADE
CONCERNING PREVIOUS HYPERSENSITIVITY REACTIONS TO PENICILLINS,
CEPHALOSPORINS, AND OTHER ALLERGENS. IF AN ALLERGIC REACTION OCCURS,
AMPICILLIN AND SULBACTAM FOR INJECTION SHOULD BE DISCONTINUED AND THE
APPROPRIATE THERAPY INSTITUTED. SERIOUS
ANAPHYLACTOID REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH
EPINEPHRINE. OXYGEN, INTRAVENOUS STEROIDS, AND AIRWAY MANAGEMENT,
INCLUDING INTUBATION, SHOULD ALSO BE ADMINISTERED AS INDICATED. Pseudomembranous colitis has been reported
with nearly all antibacterial agents, including Ampicillin and
Sulbactam for Injection, and has ranged in severity from mild to
life-threatening. Therefore, it is important to consider this
diagnosis in patients who present with diarrhea subsequent to the
administration of antibacterial agents. Treatment with
antibacterial agents alters the normal flora of the colon and may permit
overgrowth of clostridia. Studies indicate that toxin produced byClostridium difficile is one
primary cause of "antibiotic-associated colitis." Mild cases of
pseudomembranous colitis usually respond to drug discontinuation alone.
In moderate to severe cases, consideration should be given to management
with fluids and electrolytes, protein supplementation and treatment with
an antibacterial drug clinically effective against C. difficile colitis.
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| dailymed-drugs:228 |
Misuse, Abuse and Diversion of Opioids: Oxycodone is an opioid agonist of the morphine-type. Such drugs are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Oxycodone can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing oxycodone and acetaminophen tablets in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion. Concerns about misuse, addiction, and diversion should not prevent the proper management of pain. Healthcare professionals should contact their State Professional Licensing Board or State Controlled Substances Authority for information on how to prevent and detect abuse or diversion of this product. Administration of oxycodone and acetaminophen tablets should be closely monitored for the following potentially serious adverse reactions and complications:<br/>Respiratory Depression: Respiratory depression is a hazard with the use of oxycodone, one of the active ingredients in oxycodone and acetaminophen tablets, as with all opioid agonists. Elderly and debilitated patients are at particular risk for respiratory depression as are non-tolerant patients given large initial doses of oxycodone or when oxycodone is given in conjunction with other agents that depress respiration. Oxycodone should be used with extreme caution in patients with acute asthma, chronic obstructive pulmonary disorder (COPD), cor pulmonale, or preexisting respiratory impairment. In such patients, even usual therapeutic doses of oxycodone may decrease respiratory drive to the point of apnea. In these patients alternative non-opioid analgesics should be considered, and opioids should be employed only under careful medical supervision at the lowest effective dose. In case of respiratory depression, a reversal agent such as naloxone hydrochloride may be utilized .<br/>Head Injury and Increased Intracranial Pressure: The respiratory depressant effects of opioids include carbon dioxide retention and secondary elevation of cerebrospinal fluid pressure, and may be markedly exaggerated in the presence of head injury, other intracranial lesions or a preexisting increase in intracranial pressure. Oxycodone produces effects on pupillary response and consciousness which may obscure neurologic signs of worsening in patients with head injuries.<br/>Hypotensive Effect: Oxycodone may cause severe hypotension particularly in individuals whose ability to maintain blood pressure has been compromised by a depleted blood volume, or after concurrent administration with drugs which compromise vasomotor tone such as phenothiazines. Oxycodone, like all opioid analgesics of the morphine-type, should be administered with caution to patients in circulatory shock, since vasodilation produced by the drug may further reduce cardiac output and blood pressure. Oxycodone may produce orthostatic hypotension in ambulatory patients.<br/>Hepatotoxicity: Precaution should be taken in patients with liver disease. Hepatotoxicity and severe hepatic failure occurred in chronic alcoholics following therapeutic doses.
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The administration of intravenous solutions can cause fluid and/or solute overload resulting in dilution of serum electrolyte concentrations, overhydration, congested states or pulmonary edema. The risk of dilutional states is inversely proportional to the electrolyte concentration. The risk of solute overload causing congested states with peripheral and pulmonary edema is directly proportional to the electrolyte concentration. Solutions containing sodium ions should be used with great care, if at all, in patients with congestive heart failure, severe renal insufficiency, and in clinical states in which there is sodium retention with edema. Solutions containing potassium ions should be used with great care, if at all, in patients with hyperkalemia, severe renal failure, and in conditions in which potassium retention is present. In patients with diminished renal function, administration of solutions containing sodium or potassium ions may result in sodium or potassium retention. Solutions containing calcium ions should not be administered simultaneously through the same administration set as blood because of the likelihood of coagulation.
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The sulfonamides should not be used for the treatment of group A betahemolytic streptococcal infections. In an established infection, they will not eradicate the streptococcus and, therefore, will not prevent sequelae such as rheumatic fever and glomerulonephritis. Deaths associated with the administration of sulfonamides have been reported from hypersensitivity reactions, agranulocytosis, aplastic anemia, and other blood dyscrasias. The presence of such clinical signs as sore throat, fever, pallor, purpura, or jaundice may be early indications of serious blood disorders. The frequency of renal complications is considerably lower in patients receiving the more soluble sulfonamides.
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| dailymed-drugs:232 |
FOR DRUG DILUENT USE ONLY. Intravenous administration of Sterile Water for Injection, USP
without additives may result in hemolysis. The
intravenous administration of sterile water for injection with additives
can cause fluid and/or solute overloading resulting in dilution of
serum electrolyte concentrations, overhydration, congested states
or pulmonary edema. The risk of dilutional states is inversely proportional
to the electrolyte concentrations of administered parenteral solutions.
The risk of solute overload causing congested states with peripheral
and pulmonary edema is directly proportional to the electrolyte concentrations
of such solutions. WARNING: This product
contains aluminum that may be toxic. Aluminum may reach toxic levels
with prolonged parenteral administration if kidney function is impaired.
Premature neonates are particularly at risk because their kidneys
are immature, and they require large amounts of calcium and phosphate
solutions, which contain aluminum. Research
indicates that patients with impaired kidney function, including premature
neonates, who receive parenteral levels of aluminum at greater than
4 to 5 mcg/kg/day accumulate aluminum at levels associated with central
nervous system and bone toxicity. Tissue loading may occur at even
lower rates of administration.
|
| dailymed-drugs:1940 |
FOR DRUG DILUENT USE ONLY. Intravenous administration of Sterile Water for Injection, USP
without additives may result in hemolysis. The
intravenous administration of sterile water for injection with additives
can cause fluid and/or solute overloading resulting in dilution of
serum electrolyte concentrations, overhydration, congested states
or pulmonary edema. The risk of dilutional states is inversely proportional
to the electrolyte concentrations of administered parenteral solutions.
The risk of solute overload causing congested states with peripheral
and pulmonary edema is directly proportional to the electrolyte concentrations
of such solutions. WARNING: This product
contains aluminum that may be toxic. Aluminum may reach toxic levels
with prolonged parenteral administration if kidney function is impaired.
Premature neonates are particularly at risk because their kidneys
are immature, and they require large amounts of calcium and phosphate
solutions, which contain aluminum. Research
indicates that patients with impaired kidney function, including premature
neonates, who receive parenteral levels of aluminum at greater than
4 to 5 mcg/kg/day accumulate aluminum at levels associated with central
nervous system and bone toxicity. Tissue loading may occur at even
lower rates of administration.
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| dailymed-drugs:233 |
There is no evidence that mebendazole, even at high doses, is effective for hydatid disease. There have been rare reports of neutropenia and agranulocytosis when mebendazole was taken for prolonged periods and at dosages substantially above those recommended.
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| dailymed-drugs:234 |
Amiodarone hydrochloride is intended for use only in patients with the indicated life-threatening arrhythmias because its use is accompanied by substantial toxicity. Amiodarone has several potentially fatal toxicities, the most important of which is pulmonary toxicity (hypersensitivity pneumonitis or interstitial/alveolar pneumonitis) that has resulted in clinically manifest disease at rates as high as 10% to 17% in some series of patients with ventricular arrhythmias given doses around 400 mg/day, and as abnormal diffusion capacity without symptoms in a much higher percentage of patients. Pulmonary toxicity has been fatal about 10% of the time. Liver injury is common with amiodarone, but is usually mild and evidenced only by abnormal liver enzymes. Overt liver disease can occur, however, and has been fatal in a few cases. Like other antiarrhythmics, amiodaronecan exacerbate the arrhythmia, e.g., by making the arrhythmia less well tolerated or more difficult to reverse. This has occurred in 2% to 5% of patients in various series, and significant heart block or sinus bradycardia has been seen in 2% to 5%. All of these events should be manageable in the proper clinical setting in most cases. Although the frequency of such proarrhythmic events does not appear greater with amiodarone than with many other agents used in this population, the effects are prolonged whenthey occur. Even in patients at high risk of arrhythmic death, in whom the toxicity of amiodarone is an acceptable risk, amiodarone poses major management problems that could be life-threatening in a population at risk of sudden death, so that every effort should be made to utilize alternative agents first. The difficulty of using amiodarone effectively and safely itself poses a significant risk to patients. Patients with the indicated arrhythmias must be hospitalized while the loading dose of amiodarone is given and a response generally requires at least one week, usually two or more. Because absorption and elimination are variable, maintenance-dose selection is difficult, and it is not unusual to require dosage decrease or discontinuation of treatment. In a retrospective survey of 192 patients with ventricular tachyarrhythmias, 84 required dose reduction and 18 required at least temporary discontinuation because of adverse effects, and several series have reported 15% to 20% overall frequencies of discontinuation due to adverse reactions. The time at which a previously controlled life-threatening arrhythmia will recur after discontinuation or dose adjustment is unpredictable, ranging from weeks to months. The patient is obviously at great risk during this time and may need prolonged hospitalization. Attempts to substitute other antiarrhythmic agents when amiodarone must be stopped will be made difficult by the gradually, but unpredictably, changing amiodarone bodyburden. A similar problem exists when amiodarone is not effective; it still poses the risk of an interaction with whatever subsequent treatment is tried.<br/>Mortality: In the National Heart, Lung and Blood Institute's Cardiac Arrhythmia Suppression Trial (CAST), a long-term, multi-centered, randomized, double-blind study in patients with asymptomatic non-life-threatening ventricular arrhythmias who had had myocardial infarctions more than six days but less than two years previously, an excessive mortality or non-fatal cardiac arrest rate was seen in patients treated with encainide or flecainide (56/730) compared with that seen in patients assigned to matched placebo-treated groups(22/725). The average duration of treatment with encainide or flecainide in this study was ten months. Amiodarone therapy was evaluated in two multi-centered, randomized, double-blind, placebo-controlled trials involving 1202 (Canadian Amiodarone Myocardial Infarction Arrhythmia Trial; CAMIAT) and 1486 (European Myocardial Infarction Amiodarone Trial; EMIAT) post-MI patients followed for up to 2 years. Patients in CAMIAT qualified with ventricular arrhythmias, and those randomized toamiodarone received weight- and response-adjusted doses of 200 mg/day to 400 mg/day. Patients in EMIAT qualified with ejection fraction<40%, and those randomized to amiodarone received fixed doses of 200 mg/day. Both studies had weeks-long loading dose schedules. Intent-to-treat all-cause mortality results were as follows: These data are consistent with the results of a pooled analysis of smaller, controlled studies involving patients with structural heart disease (including myocardial infarction).<br/>Pulmonary Toxicity: There have been postmarketing reports of acute-onset (days to weeks) pulmonary injury in patients treated with oral amiodarone with or without initial I.V. therapy. Findings have included pulmonary infiltrates and/or mass on X-ray, pulmonary alveolar hemorrhage, bronchospasm, wheezing, fever, dyspnea, cough, hemoptysis and hypoxia. Some cases have progressed to respiratory failure and/or death. Amiodarone Hydrochloride Tablets may cause a clinical syndrome of cough and progressive dyspnea accompanied by functional, radiographic, gallium-scan and pathological data consistent with pulmonary toxicity, the frequency of which varies from 2% to 7% in most published reports, but is as high as 10% to 17% in some reports. Therefore, when amiodarone therapy is initiated, a baseline chest X-ray and pulmonary-function tests, including diffusion capacity, should be performed. The patient should return for a history, physical exam and chest X-ray every 3 to 6 months. Pulmonary toxicity secondary to amiodarone seems to result from either indirect or direct toxicity as represented by hypersensitivity pneumonitis or interstitial/alveolar pneumonitis, respectively. Patients with preexisting pulmonary disease have a poorer prognosis if pulmonary toxicity develops. Hypersensitivity Pneumonitisusually appears earlier in the course of therapy, and rechallenging these patients with amiodarone results in a more rapid recurrence of greater severity. Bronchoalveolar lavage is the procedure of choice to confirm this diagnosis, which can be made when a T suppressor/cytotoxic (CD8-positive) lymphocytosis is noted. Steroid therapy should be instituted and amiodarone therapy discontinued in these patients. Interstitial/Alveolar Pneumonitismay result from the release of oxygen radicals and/or phospholipidosis and is characterized by findings of diffuse alveolar damage, interstitial pneumonitis or fibrosis in lung biopsy specimens. Phospholipidosis (foamy cells, foamy macrophages), due to inhibition of phospholipase, will be present in most cases of amiodarone-induced pulmonary toxicity; however, these changes also are present in approximately 50% of all patients on amiodarone therapy. These cells should be used as markers of therapy, but not as evidence of toxicity. A diagnosis of amiodarone-induced interstitial/alveolar pneumonitis should lead, at a minimum, to dose reduction or, preferably, to withdrawal of the amiodarone hydrochloride to establish reversibility, especially if other acceptable antiarrhythmic therapies are available. Where these measures have been instituted, a reduction in symptoms of amiodarone-induced pulmonary toxicity was usually noted within the first week, and a clinical improvement was greatest in the first two to three weeks. Chest X-ray changes usually resolve within two to four months. According to some experts, steroids may prove beneficial. Prednisone in doses of 40 mg/day to 60 mg/day or equivalent doses of other steroids have been given and tapered over the course of several weeks depending upon the condition of the patient. In some cases rechallenge with amiodarone at a lower dose has not resulted in return of toxicity. Reports suggest that the use of lower loading and maintenance doses of amiodarone are associated with a decreased incidence of amiodarone-induced pulmonary toxicity. In a patient receiving amiodarone, any new respiratory symptoms should suggest the possibility of pulmonary toxicity and the history, physical exam, chest X-ray and pulmonary-function tests (with diffusion capacity) should be repeated and evaluated. A 15% decrease in diffusion capacity has a high sensitivity but only a moderate specificity for pulmonary toxicity; as the decrease in diffusion capacity approaches 30%, the sensitivity decreases but the specificity increases. A gallium-scan also may be performed as part of the diagnostic workup. Fatalities, secondary to pulmonary toxicity, have occurred in approximately 10% of cases. However, in patients with life-threatening arrhythmias, discontinuation of amiodarone therapy due to suspected drug-induced pulmonary toxicity should be undertaken with caution, as the most common cause of death in these patients is sudden cardiac death. Therefore, every effort should be made to rule out other causes of respiratory impairment (i.e., congestive heart failure with Swan-Ganz catheterization if necessary, respiratory infection, pulmonary embolism, malignancy, etc.) beforediscontinuing amiodarone in these patients. In addition, bronchoalveolar lavage, transbronchial lung biopsy and/or open lung biopsy may be necessary to confirm the diagnosis, especially in those cases where no acceptable alternative therapy is available. If a diagnosis of amiodarone-induced hypersensitivity pneumonitis is made, amiodarone should be discontinued and treatment with steroids should be instituted. If a diagnosis of amiodarone-induced interstitial/alveolar pneumonitis is made, steroid therapy should be instituted and, preferably, amiodarone discontinued or, at a minimum, reduced in dosage. Some cases of amiodarone-induced interstitial/alveolar pneumonitis may resolve following a reduction in amiodarone dosage in conjunction with the administration of steroids. In some patients, rechallenge at a lower dose has not resulted in return of interstitial/alveolar pneumonitis; however, in some patients (perhaps because of severe alveolar damage) the pulmonary lesions have not beenreversible.<br/>Worsened Arrhythmia: Amiodarone, like other antiarrhythmics, can cause serious exacerbation of the presenting arrhythmia, a risk that may be enhanced by the presence of concomitant antiarrhythmics. Exacerbation has been reported in about 2% to 5% in most series, and has included new ventricular fibrillation, incessant ventricular tachycardia, increased resistance to cardioversion, and polymorphic ventricular tachycardia associated with QTc prolongation (torsades de pointes [TdP]). In addition, amiodarone has caused symptomatic bradycardia or sinus arrest with suppression of escape foci in 2% to 4% of patients. Fluoroquinolones, macrolide antibiotics, and azoles are known to cause QTc prolongation. There have been reports of QTc prolongation, with or without TdP, in patients taking amiodarone when fluoroquinolones, macrolide antibiotics, or azoles were administered concomitantly. (See Drug Interactions, Other reported interactions with amiodarone.) The need to co-administer amiodarone with any other drug known to prolong the QTc interval must be based on a careful assessment of the potential risks and benefits of doing so for each patient. A careful assessment of the potential risks and benefits of administering amiodarone must be made in patients with thyroid dysfunction due to the possibility of arrhythmia breakthrough or exacerbation of arrhythmia in these patients.<br/>Thyrotoxicosis: Amiodarone-induced hyperthyroidism may result in thyrotoxicosis and/or the possibility of arrhythmia breakthrough or aggravation. There have been reports of death associated with amiodarone-induced thyrotoxicosis. IF ANY NEW SIGNS OF ARRHYTHMIA APPEAR, THE POSSIBILITY OF HYPERTHYROIDISM SHOULD BE CONSIDERED .<br/>Liver Injury: Elevations of hepatic enzyme levels are seen frequently in patients exposed to amiodarone and in most cases are asymptomatic. If the increase exceeds three times normal, or doubles in a patient with an elevated baseline, discontinuation of amiodarone or dosage reduction should be considered. In a few cases in which biopsy has been done, the histology has resembled that of alcoholic hepatitis or cirrhosis. Hepatic failure has been a rare cause of death in patients treated with amiodarone.<br/>Loss of Vision: Cases of optic neuropathy and/or optic neuritis, usually resulting in visual impairment, have been reported in patients treated with amiodarone. In some cases, visual impairment has progressed to permanent blindness. Optic neuropathy and/or neuritis may occur at any time following initiation of therapy. A causal relationship to the drug has not been clearly established. If symptoms of visual impairment appear, such as changesin visual acuity and decreases in peripheral vision, prompt ophthalmic examination is recommended. Appearance of optic neuropathy and/or neuritis calls for re-evaluation of amiodarone therapy. The risks and complications of antiarrhythmic therapy with amiodarone must be weighed against its benefits in patients whose lives are threatened by cardiac arrhythmias. Regular ophthalmic examination, including funduscopy and slit-lamp examination, is recommended during administration of amiodarone .<br/>Neonatal Hypo- or Hyperthyroidism: Amiodarone can cause fetal harm when administered to a pregnant woman. Although amiodarone use during pregnancy is uncommon, there have been a small number of published reports of congenital goiter/hypothyroidism and hyperthyroidism. If amiodarone is used during pregnancy or if the patient becomes pregnant while taking amiodarone, the patient should be apprised of the potential hazard to the fetus. In general, Amiodarone Hydrochloride Tablets should be used during pregnancy only if the potential benefit to the mother justifies the unknown risk to the fetus. In pregnant rats and rabbits, amiodarone HCl in doses of 25 mg/kg/day (approximately 0.4 and 0.9 times, respectively, the maximum recommended human maintenance dose*) had no adverse effects on the fetus. In the rabbit, 75 mg/kg/day (approximately 2.7 times the maximum recommended human maintenance dose*) caused abortions in greater than 90% of the animals. In the rat, doses of 50 mg/kg/day or more were associated with slight displacement of the testes and an increased incidence of incomplete ossification of some skull and digital bones; at 100 mg/kg/day or more, fetal body weights were reduced; at 200 mg/kg/day, there was an increased incidence of fetal resorption. (These doses in the rat are approximately 0.8, 1.6 and 3.2 times the maximum recommended human maintenance dose*.) Adverse effects on fetal growth and survival also were noted in one of two strains of mice at a dose of 5 mg/kg/day (approximately 0.04 times the maximum recommended human maintenance dose*). *600 mg in a 50 kg patient (doses compared on a body surface area basis)
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| dailymed-drugs:237 |
1. ESTROGENS HAVE BEEN REPORTED TO INCREASE THE RISK OF ENDOMETRIAL CARCINOMA IN POSTMENOPAUSAL WOMEN. Close clinical surveillance of all women taking estrogens is important. Adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding. There is no evidence that "natural" estrogens are more or less hazardous than "synthetic" estrogens at equiestrogenic doses. 2. ESTROGEN SHOULD NOT BE USED DURING PREGNANCY. There is no indication for estrogen therapy during pregnancy or during the immediate postpartum period. Estrogens are ineffective for the prevention or treatment of threatened or habitual abortion. Estrogens are not indicated for the prevention of postpartum breast engorgement. Estrogen therapy during pregnancy is associated with an increased risk of congenital defects in the reproductive organs of the fetus, and possibly other birth defects. Studies of women who received diethylstilbestrol (DES) during pregnancy have shown that female offspring have an increased risk of vaginal adenosis, squamous cell dysplasia of the uterine cervix, and clear cell vaginal cancer later in life; male offspring have an increased risk of urogenital abnormalities and possibly testicular cancer later in life. The 1985 DES Task Force concluded that use of DES during pregnancy is associated with a subsequent increased risk of breast cancer in the mothers, although a causal relationship remains unproven and the observed level of excess risk is similar to that for a number of other breast cancer risk factors.
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| dailymed-drugs:238 |
Excessive administration of potassium-free solutions
may result in significant hypokalemia. The
intravenous administration of these solutions can cause fluid and/or
solute overloading resulting in dilution of serum electrolyte concentrations,
overhydration, congested states or pulmonary edema. The risk of dilutional states is inversely proportional to the
electrolyte concentrations of administered parenteral solutions. The
risk of solute overload causing congested states with peripheral and
pulmonary edema is directly proportional to the electrolyte concentrations
of such solutions.
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| dailymed-drugs:2053 |
Excessive administration of potassium-free solutions
may result in significant hypokalemia. The
intravenous administration of these solutions can cause fluid and/or
solute overloading resulting in dilution of serum electrolyte concentrations,
overhydration, congested states or pulmonary edema. The risk of dilutional states is inversely proportional to the
electrolyte concentrations of administered parenteral solutions. The
risk of solute overload causing congested states with peripheral and
pulmonary edema is directly proportional to the electrolyte concentrations
of such solutions.
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| dailymed-drugs:239 |
In patients on corticosteroid therapy subjected to unusual stress, increased dosage of rapidly acting corticosteroids, before, during, and after the stressful situation is indicated. Corticosteroids may mask some signs of infection, and new infections may appear during their use. There may be decreased resistance and inability to localize infection when corticosteroids are used. Prolonged use of corticosteroids may produce posterior subcapsular cataracts, glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infections due to fungi or viruses.<br/>Usage in pregnancy:: Since adequate human reproduction studies have not been done with corticosteroids, the use of these drugs in pregnancy, nursing mothers or women of childbearing potential requires that the possible benefits of the drug be weighed against the potential hazards to the mother and embryo or fetus. Infants born of mothers whohave received substantial doses of corticosteroids during pregnancy, should be carefully observed for signs of hypoadrenalism. Average and large doses of hydrocortisone or cortisone can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium.
These effects are less likely to occur with the synthetic derivatives except when used in large doses. Dietary salt restriction and potassium supplementation may be necessary. All corticosteroids increase calcium excretion. While on corticosteroid therapy patients should not be vaccinated against smallpox. Other immunization procedures should not be undertaken in patients who are on corticosteroids, especially on high dose, because of possible hazards of neurological complications and a lack of antibody response. The use of PredniSONE Tablets in active tuberculosis should be restricted to those cases of fulminating or disseminated tuberculosis in which the corticosteroid is used for the management of the disease in conjunction with an appropriate anti-tuberculous regimen. If corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary as reactivation of the disease may occur. During prolonged corticosteroid therapy, these patients should receive chemoprophylaxis. Persons who are on drugs which suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in non-immune children or adults on corticosteroids. In such children or adults who have not had these diseases, particular care should be taken to avoid exposure. How the dose, route and duration of corticosteroid administration affects the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If chickenpox develops, treatment with antiviral agents may be considered.
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| dailymed-drugs:240 |
Hepatic Injury: Severe hepatocellular injury, confirmed by rechallenge in at least one case, occurs rarely with therapy with labetalol. The hepatic injury is usually reversible, but hepatic necrosis and death have been reported. Injury has occurred after both short- and long-term treatment and may be slowly progressive despite minimal symptomatology. Similar hepatic events have been reported with a related compound, dilevalol HCl, including two deaths. Dilevalol HCl is one of the four isomers of labetalol HCl. Thus, for patients taking labetalol, periodic determination of suitable hepatic laboratory tests would be appropriate. Laboratory testing should also be done at the very first symptom or sign of liver dysfunction (e.g., pruritus, dark urine, persistent anorexia, jaundice, right upper quadrant tenderness, or unexplained���flu-like���symptoms). If the patient has jaundice or laboratory evidence of liver injury, labetalol should be stopped and not restarted.<br/>Cardiac Failure: Sympathetic stimulation is a vital component supporting circulatory function in congestive heart failure. Beta blockade carries a potential hazard of further depressing myocardial contractility and precipitating more severe failure. Although beta-blockers should be avoided in overt congestive heart failure, if necessary, labetalol can be used with caution in patients with a history of heart failure who are well-compensated. Congestive heart failure has been observed in patients receiving labetalol HCl. Labetalol does not abolish the inotropic action of digitalis on heart muscle.<br/>In Patients Without a History of Cardiac Failure: In patients with latent cardiac insufficiency, continued depression of the myocardium with beta-blocking agents over a period of time can, in some cases, lead to cardiac failure. At the first sign or symptom of impending cardiac failure, patients should be fully digitalized and/or be given a diuretic, and the response observed closely. If cardiac failure continues, despite adequate digitalization and diuretic, therapy with labetalol should be withdrawn (gradually if possible).<br/>Exacerbation of Ischemic Heart Disease Following Abrupt Withdrawal: Angina pectoris has not been reported upon labetalol discontinuation. However, hypersensitivity to catecholamines has been observed in patients withdrawn from beta-blocker therapy; exacerbation of angina and, in some cases, myocardial infarction have occurred after abrupt discontinuation of such therapy. When discontinuing chronically administered labetalol, particularlyin patients with ischemic heart disease, the dosage should be gradually reduced over a period of 1 to 2 weeks and the patient should be carefully monitored. If angina markedly worsens or acute coronary insufficiency develops, labetalol administration should be reinstituted promptly, at least temporarily, and other measures appropriate for the management of unstable angina should be taken. Patients should be warned against interruption or discontinuation of therapy without the physician's advice. Because coronary artery disease is common and may be unrecognized, it may be prudent not to discontinue therapy with labetalol abruptly even in patients treated only for hypertension. Nonallergic bronchospasm (e.g., chronic bronchitis and emphysema) patients with bronchospastic disease should, in general, not receive beta-blockers. Labetalol may be used with caution, however, in patients who do not respond to, or cannot tolerate, other antihypertensive agents. It is prudent, if labetalol is used, to use the smallest effective dose, so that inhibition of endogenous or exogenous beta-agonists is minimized.<br/>Pheochromocytoma: Labetalol has been shown to be effective in lowering the blood pressure and relieving symptoms in patients with pheochromocytoma. However, paradoxical hypertensive responses have been reported in a few patients with this tumor; therefore, use caution when administering labetalol to patients with pheochromocytoma.<br/>Diabetes Mellitus and Hypoglycemia: Beta-adrenergic blockade may prevent the appearance of premonitory signs and symptoms (e.g., tachycardia) of acute hypoglycemia. This is especially important with labile diabetics. Beta-blockade also reduces the release of insulin in response to hyperglycemia; it may therefore be necessary to adjust the dose of antidiabetic drugs.<br/>Major Surgery: The necessity or desirability of withdrawing beta-blocking therapy prior to major surgery is controversial. Protracted severe hypotension and difficulty in restarting or maintaining a heartbeat have been reported with beta-blockers. The effect of labetalol's alpha-adrenergic activity has not been evaluated in this setting. A synergism between labetalol and halothane anesthesia has been shown .
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| dailymed-drugs:243 |
ARIMIDEX can cause fetal harm when administered to a pregnant woman. Anastrozole has been found to cross the placenta following oral administration of 0.1 mg/kg in rats and rabbits (about 1 and 1.9 times the recommended human dose, respectively, on a mg/mbasis). Studies in both rats and rabbits at doses equal to or greater than 0.1 and 0.02 mg/kg/day, respectively (about 1 and 1/3, respectively, the recommended human dose on a mg/mbasis), administered during the period of organogenesis showed that anastrozole increased pregnancy loss (increased pre- and/or post-implantation loss, increased resorption, and decreased numbers of live fetuses); effects were dose related in rats. Placental weights were significantly increased in rats at doses of 0.1 mg/kg/day or more. Evidence of fetotoxicity, including delayed fetal development (i.e., incomplete ossification and depressed fetal body weights), was observed in rats administered doses of 1 mg/kg/day (which produced plasma anastrozole Cand AUCthat were 19 times and 9 times higher than the respective values found in postmenopausal volunteers at the recommended dose). There was no evidence of teratogenicity in rats administered doses up to 1.0 mg/kg/day. In rabbits, anastrozole caused pregnancy failure at doses equal to or greater than 1.0 mg/kg/day (about 16 times the recommended human dose on a mg/mbasis); there was no evidence of teratogenicity in rabbits administered 0.2 mg/kg/day (about 3 times the recommended human dose on a mg/mbasis). There are no adequate and well-controlled studies in pregnant women using ARIMIDEX. If ARIMIDEX is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus or potential risk for loss of the pregnancy.
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| dailymed-drugs:245 |
Intravenous infusion of amino acids may induce a rise in
blood urea nitrogen (BUN), especially in patients with impaired hepatic or
renal function. Appropriate laboratory tests should be performed periodically
and infusion discontinued or nitrogen content reduced if BUN levels continue
to rise inappropriately. Administration of nitrogen
in any form to patients with marked hepatic insufficiency may result in serum
amino acid imbalances or CNS complications. Aminosyn-RF 5.2%, Sulfite-Free,
(an amino acid injection���renal formula), therefore, should be used
with caution in such patients. Solutions containing
acetate ion should be used with great care in patients with metabolic or respiratory
alkalosis. Hyperammonemia is of special significance
in infants, as it can result in mental retardation. Therefore, it is essential
that blood ammonia levels be measured frequently in infants. Aminosyn-RF
5.2% does not replace dialysis and conventional supportive therapy in patients
with renal failure. WARNING: This product contains aluminum
that may be toxic. Aluminum may reach toxic levels with prolonged parenteral
administration if kidney function is impaired. Premature neonates are particularly
at risk because their kidneys are immature, and they require large amounts
of calcium and phosphate solutions, which contain aluminum. Research
indicates that patients with impaired kidney function, including premature
neonates, who receive parenteral levels of aluminum at greater than 4 to 5
mcg/kg/day accumulate aluminum at levels associated with central nervous system
and bone toxicity. Tissue loading may occur at even lower rates of administration.
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| dailymed-drugs:246 |
Nursing Mothers: It is not known whether this drug is excreted in human milk. Since many drugs are so excreted, hydroxyzine should not be given to nursing mothers.
|
| dailymed-drugs:2556 |
Nursing Mothers: It is not known whether this drug is excreted in human milk. Since many drugs are so excreted, hydroxyzine should not be given to nursing mothers.
|
| dailymed-drugs:2983 |
Nursing Mothers: It is not known whether this drug is excreted in human milk. Since many drugs are so excreted, hydroxyzine should not be given to nursing mothers.
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| dailymed-drugs:248 |
THE USE OF FLUMAZENIL HAS BEEN ASSOCIATED WITH THE OCCURRENCE OF SEIZURES. THESE ARE MOST FREQUENT IN PATIENTS WHO HAVE BEEN ON BENZODIAZEPINES FOR LONG-TERM SEDATION OR IN OVERDOSE CASES WHERE PATIENTS ARE SHOWING SIGNS OF SERIOUS CYCLIC ANTI- DEPRESSANT OVERDOSE. PRACTITIONERS SHOULD INDIVIDUALIZE THE DOSAGE OF FLUMAZENIL AND BE PREPARED TO MANAGE SEIZURES.<br/>Risk of Seizures: The reversal of benzodiazepine effects may be associated with the onset of seizures in certain high-risk populations. Possible risk factors for seizures include: concurrent major sedative-hypnotic drug withdrawal, recent therapy with repeated doses of parenteral benzodiazepines, myoclonic jerking or seizure activity prior to flumazenil administration in overdose cases, or concurrent cyclic antidepressant poisoning. Flumazenil is not recommended in cases of serious cyclic antidepressant poisoning, as manifested by motor abnormalities (twitching, rigidity, focal seizure), dysrhythmia (wide QRS, ventricular dysrhythmia, heart block), anticholinergic signs (mydriasis, dry mucosa, hypoperistalsis), and cardiovascular collapse at presentation. In such cases flumazenil should be withheld and the patient should be allowed to remain sedated (with ventilatory and circulatory support as needed) until the signs of antidepressant toxicity have subsided. Treatment with flumazenil has no known benefit to the seriously ill mixed-overdose patient other than reversing sedation and should not be used in cases where seizures (from any cause) are likely. Most convulsions associated with flumazenil administration require treatment and have been successfully managed with benzodiazepines, phenytoin or barbiturates. Because of the presence of flumazenil, higher than usual doses of benzodiazepines may be required.<br/>Hypoventilation: Patients who have received flumazenil for the reversal of benzodiazepine effects (after conscious sedation or general anesthesia) should be monitored for resedation, respiratory depression, or other residual benzodiazepine effects for an appropriate period (up to 120 minutes) based on the dose and duration of effect of the benzodiazepine employed. This is because flumazenil has not been established in patients as an effective treatment for hypoventilation due to benzodiazepine administration. In healthy male volunteers, flumazenil is capable of reversing benzodiazepine-induced depression of the ventilatory responses to hypercapnia and hypoxia after a benzodiazepine alone. However, such depression may recur because the ventilatory effects of typical doses of flumazenil (1 mg or less) may wear off before the effects of many benzodiazepines. The effects of flumazenil on ventilatory response following sedation with a benzodiazepine in combination with an opioid are inconsistent and have not been adequately studied. The availability of flumazenil does not diminish the need for prompt detection of hypoventilation and the ability to effectively intervene by establishing an airway and assisting ventilation. Overdose cases should always be monitored for resedation until the patients are stable and resedation is unlikely.
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