| 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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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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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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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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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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