Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/3227
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Diltiazem Hydrochloride (Injection, Solution)
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Direct Intravenous Single Injections
(Bolus) The initial dose of Diltiazem Hydrochloride
Injection should be 0.25 mg/kg actual body weight as a bolus administered
over 2 minutes (20 mg is a reasonable dose for the average patient). If response
is inadequate, a second dose may be administered after 15 minutes. The second
bolus dose of diltiazem hydrochloride injection should be 0.35 mg/kg actual
body weight administered over 2 minutes (25 mg is a reasonable dose for the
average patient). Subsequent intravenous bolus doses should be individualized
for each patient. Patients with low body weights should be dosed on a mg/kg
basis. Some patients may respond to an initial dose of 0.15 mg/kg, although
duration of action may be shorter. Experience with this dose is limited. Continuous Intravenous Infusion For
continued reduction of the heart rate (up to 24 hours) in patients with atrial
fibrillation or atrial flutter, an intravenous infusion of diltiazem hydrochloride
may be administered. Immediately following bolus administration of 20 mg (0.25
mg/kg) or 25 mg (0.35 mg/kg) diltiazem hydrochloride injection and reduction
of heart rate, begin an intravenous infusion of diltiazem hydrochloride. The
recommended initial infusion rate of diltiazem hydrochloride is 10 mg/h. Some
patients may maintain response to an initial rate of 5 mg/h. The infusion
rate may be increased in 5 mg/h increments up to 15 mg/h as needed, if further
reduction in heart rate is required. The infusion may be maintained for up
to 24 hours. Diltiazem shows dose-dependent, non-linear
pharmacokinetics. Duration of infusion longer than 24 hours and infusion rates
greater than 15 mg/h have not been studied. Therefore, infusion duration exceeding
24 hours and infusion rates exceeding 15 mg/h are not recommended. Dilution: To prepare diltiazem hydrochloride injection
for continuous intravenous infusion aseptically transfer the appropriate quantity
(see chart) of diltiazem hydrochloride injection to the desired volume of
either Normal Saline, D5W, or D5W/0.45% NaCl. Mix thoroughly. Use within 24
hours. Keep refrigerated until use. *5 mg/h may be appropriate for some patients. Compatibility: Diltiazem
hydrochloride injection was tested for compatibility with three commonly used
intravenous fluids at a maximal concentration of 1 mg diltiazem hydrochloride
per milliliter. Diltiazem hydrochloride injection was found to be physically
compatible and chemically stable in the following parenteral solutions for
at least 24 hours when stored in glass or polyvinylchloride (PVC) bags at
controlled room temperature 20 to 25��C (68 to 77��F) [see USP] or
under refrigeration 2 to 8��C (36 to 46��F). ���dextrose (5%) injection USP ���sodium chloride
(0.9%) injection USP ���dextrose (5%) and sodium
chloride (0.45%) injection USP Physical
Incompatibilities: Because of potential physical
incompatibilities, it is recommended that diltiazem hydrochloride not be mixed
with any other drugs in the same container. If possible, it is recommended
that diltiazem hydrochloride not be coinfused in the same intravenous line.
Parenteral drug products should be inspected visually for particulate matter
and discoloration prior to administration whenever solution and container
permit. Diltiazem Hydrochloride.Physical incompatibilities (precipitate formation or cloudiness)
were observed when diltiazem hydrochloride was infused in the same intravenous
line with the following drugs: acetazolamide, acyclovir, aminophylline, ampicillin,
ampicillin sodium/sulbactam sodium, cefamandole, cefoperazone, diazepam, furosemide,
hydrocortisone sodium succinate, insulin, (regular: 100 units/mL), methylprednisolone
sodium succinate, mezlocillin, nafcillin, phenytoin, rifampin, and sodium
bicarbonate. Transition to
Further Antiarrhythmic Therapy Transition
to other antiarrhythmic agents following administration of diltiazem hydrochloride
injection is generally safe. However, reference should be made to the respective
agent manufacturer's package insert for information relative to dosage
and administration. In controlled clinical trials, therapy
with antiarrhythmic agents to maintain reduced heart rate in atrial fibrillation
or atrial flutter or for prophylaxis of PSVT was generally started within
3 hours after bolus administration of diltiazem. These antiarrhythmic agents
were intravenous or oral digoxin, Class 1 antiarrhythmics (e.g., quinidine,
procainamide), calcium channel blockers, and oral beta-blockers. Experience
in the use of antiarrhythmic agents following maintenance infusion of diltiazem
hydrochloride injection is limited. Patients should be dosed on an individual
basis and reference should be made to the respective manufacturer's package
insert for information relative to dosage and administration.
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Diltiazem Hydrochloride Injection is a calcium ion influx
inhibitor (slow channel blocker or calcium channel antagonist). Chemically,
diltiazem hydrochloride is 1,5-benzothiazepin-4(5H)-one, 3-(acetyloxy)-5-[2-(dimethylamino)ethyl]-2, 3-dihydro-2-(4-methoxyphenyl)-,
monohydrochloride,(+)-cis-. The chemical structure is: Diltiazem hydrochloride is a white to off-white crystalline
powder with a bitter taste. It is soluble in water, methanol, and chloroform.
It has a molecular weight of 450.98. Diltiazem hydrochloride
injection is a clear, colorless, sterile, nonpyrogenic solution. pH is 3.9
(3.7 to 4.1). Diltiazem Hydrochloride Injection is for
direct intravenous bolus injection and continuous intravenous infusion. Each
mL contains 5 mg of diltiazem hydrochloride, 0.75 mg citric acid USP, 0.65
mg sodium citrate (dihydrate) USP, 71.4 mg sorbitol solution USP, and water
for injection USP. May contain sodium hydroxide and/or hydrochloric acid for
pH adjustment. pH is 3.9 (3.7 to 4.1).
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Mechanisms of Action Diltiazem
inhibits the influx of calcium (Ca+) ions during membrane depolarization
of cardiac and vascular smooth muscle. The therapeutic benefits of diltiazem
in supraventricular tachycardias are related to its ability to slow AV nodal
conduction time and prolong AV nodal refractoriness. Diltiazem exhibits frequency
(use) dependent effects on AV nodal conduction such that it may selectively
reduce the heart rate during tachycardias involving the AV node with little
or no effect on normal AV nodal conduction at normal heart rates. Diltiazem
slows the ventricular rate in patients with a rapid ventricular response during
atrial fibrillation or atrial flutter. Diltiazem converts paroxysmal supraventricular
tachycardia (PSVT) to normal sinus rhythm by interrupting the reentry circuit
in AV nodal reentrant tachycardias and reciprocating tachycardias, e.g., Wolff-Parkinson-White
syndrome (WPW). Diltiazem prolongs the sinus cycle length.
It has no effect on the sinus node recovery time or on the sinoatrial conduction
time in patients without SA nodal dysfunction. Diltiazem has no significant
electrophysiologic effect on tissues in the heart that are fast sodium channel
dependent, e.g., His-Purkinje tissue, atrial and ventricular muscle, and extranodal
accessory pathways. Like other calcium channel antagonists,
because of its effect on vascular smooth muscle, diltiazem decreases total
peripheral resistance resulting in a decrease in both systolic and diastolic
blood pressure. Hemodynamics In patients with cardiovascular disease,
diltiazem hydrochloride administered intravenously in single bolus doses,
followed in some cases by a continuous infusion, reduced blood pressure, systemic
vascular resistance, the rate-pressure product, and coronary vascular resistance
and increased coronary blood flow. In a limited number of studies of patients
with compromised myocardium (severe congestive heart failure, acute myocardial
infarction, hypertrophic cardiomyopathy), administration of intravenous diltiazem
produced no significant effect on contractility, left ventricular end diastolic
pressure, or pulmonary capillary wedge pressure. The mean ejection fraction
and cardiac output/index remained unchanged or increased. Maximal hemodynamic
effects usually occurred within 2 to 5 minutes of an injection. However, in
rare instances, worsening of congestive heart failure has been reported in
patients with preexisting impaired ventricular function. Pharmacodynamics The prolongation
of PR interval correlated significantly with plasma diltiazem concentration
in normal volunteers using the Sigmoidal Emodel. Changes in
heart rate, systolic blood pressure, and diastolic blood pressure did not
correlate with diltiazem plasma concentrations in normal volunteers. Reduction
in mean arterial pressure correlated linearly with diltiazem plasma concentration
in a group of hypertensive patients. In patients with
atrial fibrillation and atrial flutter, a significant correlation was observed
between the percent reduction in HR and plasma diltiazem concentration using
the Sigmoidal Emodel. Based on this relationship, the mean
plasma diltiazem concentration required to produce a 20% decrease in heart
rate was determined to be 80 ng/mL. Mean plasma diltiazem concentrations of
130 ng/mL and 300 ng/mL were determined to produce reductions in heart rate
of 30% and 40%. Pharmacokinetics
and Metabolism Following a single intravenous
injection in healthy male volunteers, diltiazem hydrochloride appears to obey
linear pharmacokinetics over a dose range of 10.5 to 21 mg. The plasma elimination
half-life is approximately 3.4 hours. The apparent volume of distribution
of diltiazem is approximately 305 L. Diltiazem is extensively metabolized
in the liver with a systemic clearance of approximately 65 L/h. After
constant rate intravenous infusion to healthy male volunteers, diltiazem exhibits
nonlinear pharmacokinetics over an infusion range of 4.8 to 13.2 mg/h for
24 hours. Over this infusion range, as the dose is increased, systemic clearance
decreases from 64 to 48 L/h while the plasma elimination half-life increases
from 4.1 to 4.9 hours. The apparent volume of distribution remains unchanged
(360 to 391 L). In patients with atrial fibrillation or atrial flutter, diltiazem
systemic clearance has been found to be decreased compared to healthy volunteers.
In patients administered bolus doses ranging from 2.5 mg to 38.5 mg, systemic
clearance averaged 36 L/h. In patients administered continuous infusions at
10 mg/h or 15 mg/h for 24 hours, diltiazem systemic clearance averaged 42
L/h and 31 L/h, respectively. Based on the results of
pharmacokinetic studies in healthy volunteers administered different oral diltiazem hydrochloride formulations,
constant rate intravenous infusions of diltiazem hydrochloride at 3, 5, 7,
and 11 mg/h are predicted to produce steady-state plasma diltiazem concentrations
equivalent to 120-, 180-, 240-, and 360-mg total daily oral doses of diltiazem
hydrochloride tablets and diltiazem hydrochloride extended-release capsules. After
oral administration, diltiazem undergoes extensive metabolism in man by deacetylation,
N-demethylation, and O-demethylation via cytochrome P-450 (oxidative metabolism)
in addition to conjugation. Metabolites N-monodesmethyldiltiazem, desacetyldiltiazem,
desacetyl-N-monodesmethyldiltiazem, desacetyl-O-desmethyldiltiazem, and desacetyl-N,
O-desmethyldiltiazem have been identified in human urine. Following oral administration,
2% to 4% of the unchanged diltiazem appears in the urine. Drugs which induce
or inhibit hepatic microsomal enzymes may alter diltiazem disposition. Following
single intravenous injection of diltiazem hydrochloride, however, plasma concentrations
of N-monodesmethyldiltiazem and desacetyldiltiazem, two principal metabolites
found in plasma after oral administration, are typically not detected. These
metabolites are observed, however, following 24 hour constant rate intravenous
infusion. Total radioactivity measurement following short IV administration
in healthy volunteers suggests the presence of other unidentified metabolites
which attain higher concentrations than those of diltiazem and are more slowly
eliminated; half-life of total radioactivity is about 20 hours compared to
2 to 5 hours for diltiazem. Diltiazem is 70% to 80%
bound to plasma proteins. In vitro studies
suggest alpha���acid glycoprotein binds approximately 40%
of the drug at clinically significant concentrations. Albumin appears to bind
approximately 30% of the drug, while other constituents bind the remaining
bound fraction. Competitive in vitro ligand
binding studies have shown that diltiazem binding is not altered by therapeutic
concentrations of digoxin, phenytoin, hydrochlorothiazide, indomethacin, phenylbutazone,
propranolol, salicylic acid, tolbutamide,or warfarin. Renal
insufficiency, or even end-stage renal disease, does not appear to influence
diltiazem disposition following oral administration.
Liver cirrhosis was shown to reduce diltiazem's apparent oralclearance and prolong its half-life.
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Diltiazem hydrochloride injection is contraindicated in:
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Diltiazem Hydrochloride Injection is supplied in single-dose
containers as follows: DISCARD UNUSED PORTION. STORE PRODUCT
UNDER REFRIGERATION 2 TO 8��C (36 TO 46��F). DO NOT FREEZE. MAY
BE STORED AT ROOM TEMPERATURE FOR UP TO 1 MONTH. DESTROY AFTER 1 MONTH AT
ROOM TEMPERATURE. Revised: June, 2006 ��Hospira
2006 EN-1220 Printed in USA HOSPIRA,
INC., LAKE FOREST, IL 60045 USA
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General: Diltiazem hydrochloride is extensively metabolized by the
liver and excreted by the kidneys and in bile. The drug should be used with
caution in patients with impaired renal or hepatic function (see WARNINGS). High intravenous dosages (4.5
mg/kg tid) administered to dogs resulted in significant bradycardia and alterations
in AV conduction. In subacute and chronic dog and rat studies designed to
produce toxicity, high oral doses of diltiazem were associated with hepatic
damage. In special subacute hepatic studies, oral doses of 125 mg/kg and higher
in rats were associated with histological changes in the liver, which were
reversible when the drug was discontinued. In dogs, oral doses of 20 mg/kg
were also associated with hepatic changes; however, these changes were reversible
with continued dosing. Dermatologic events progressing
to erythema multiforme and/or exfoliative dermatitis have been infrequently
reported following oral diltiazem. Therefore, the potential for these dermatologic
reactions exists following exposure to intravenous diltiazem. Should a dermatologic
reaction persist, the drug should be discontinued.<br/>Drug Interactions: As with all drugs, care should be exercised when treating
patients with multiple medications. Diltiazem is both a substrate and an inhibitor
of the cytochrome P-450 3A4 enzyme system. Other drugs that are specific substrates,
inhibitors, or inducers of this enzyme system may have a significant impact
on the efficacy and side effect profile of diltiazem. Patients taking other
drugs that are substrates of CYP450 3A4, especially patients with renal and/or
hepatic impairment, may require dosage adjustment when starting or stopping
concomitantly administered diltiazem in order to maintain optimum therapeutic
blood levels. Anesthetics.The depression of cardiac contractility, conductivity, and automaticity
as well as the vascular dilation associated with anesthetics may be potentiated
by calcium channel blockers. When used concomitantly, anesthetics and calcium
blockers should be titrated carefully. Benzodiazepines.Studies showed that diltiazem increased the AUC of midazolam and
triazolam by 3-4 fold and Cby 2-fold, compared to placebo.
The elimination half-life of midazolam and triazolam also increased (1.5-2.5
fold) during coadministration with diltiazem. These pharmacokinetic effects
seen during diltiazem coadministration can result in increased clinical effects
(e.g., prolonged sedation) of both midazolam and triazolam. Beta-blockers. Intravenous diltiazem has been administered
to patients on chronic oral beta-blocker therapy. The combination of the two
drugs was generally well tolerated without serious adverse effects. If intravenous
diltiazem is administered to patients receiving chronic oral beta-blocker
therapy, the possibility for bradycardia, AVblock, and/or depression of contractility
should be considered (see CONTRAINDICATIONS). Oral administrationof diltiazem with propranolol in five normal volunteers resulted in increased
propranolol levels in all subjects and bioavailability of propranolol was
increased approximately 50%. In vitro,
propranolol appears to be displaced from its binding sites by diltiazem. Buspirone. In nine healthy subjects, diltiazem
significantly increased the mean buspirone AUC 5.5 fold and C4.1
fold compared to placebo. The Tand Tof buspirone
were not significantly affected by diltiazem. Enhanced effects and increased
toxicity of buspirone may be possible during concomitant administration with
diltiazem. Subsequent dose adjustments may be necessary during co-administration,
and should be based on clinical assessment. Carbamazepine. Concomitant administration of oral diltiazem with carbamazepine has been
reported to result in elevated plasma levels of carbamazepine (by 40 to 72%),
resulting in toxicity in some cases. Patients receiving these drugs concurrently
should be monitored for a potential drug interaction. Cimetidine. A study in six healthy volunteers has
shown a significant increase in peak diltiazem plasma levels (58%) and area-under-the-curve
(53%) after a 1-week course of cimetidine at 1200 mg per day and a single
dose of diltiazem 60 mg. Ranitidine produced smaller, nonsignificant increases.
The effect maybe mediated by cimetidine's known inhibition of hepatic
cytochrome P-450, the enzyme system responsible for the first-pass metabolism
of diltiazem. Patients currently receiving diltiazem therapy should be carefully
monitored for a change in pharmacological effect when initiating and discontinuing
therapy with cimetidine. An adjustment in the diltiazem dose may be warranted. Cyclosporine. A pharmacokinetic interaction between
diltiazem and cyclosporine has been observed during studies involving renal
and cardiac transplant patients. In renal and cardiac transplant recipients,
a reduction of cyclosporine dose ranging from 15% to 48% was necessary to
maintain cyclosporine trough concentrations similar to those seen prior to
the addition of diltiazem. If these agents are to be administered concurrently,
cyclosporine concentrations should be monitored, especially when diltiazem
therapy is initiated, adjusted or discontinued. The
effect of cyclosporine on diltiazem plasma concentrations has not been evaluated. Digitalis. Intravenous diltiazem has been administered
to patients receiving either intravenous or oral digitalis therapy. The combination
of the two drugs was well tolerated without serious adverse effects. However,
since both drugs affect AV nodal conduction, patients should be monitored
for excessive slowing of the heart rate and/or AV block. Lovastatin. In a ten-subject study, coadministration
of diltiazem (120 mg bid, diltiazem SR) with lovastatin resulted in a 3-4
times increase in mean lovastatin AUC and Cversus lovastatin
alone; no change in pravastatin AUC and Cwas observed during
diltiazem coadministration. Diltiazem plasma levels were not significantly
affected by lovastatin or pravastatin. Quinidine.Diltiazem significantly increases the AUC���of
quinidine by 51%, Tby 36% and decreases its CLby
33%. Monitoring for quinidine adverse effects may be warranted and the dose
adjusted accordingly. Rifampin.Coadministration of rifampin with diltiazem lowered the diltiazem
plasma concentrations to undetectable levels. Coadministration of diltiazem
with rifampin or any known CYP3A4 inducer should be avoided when possible,
and alternative therapy considered.<br/>Carcinogenesis, Mutagenesis, Impairment of Fertility: A 24-month study in rats at oral dosage levels of up to 100
mg/kg/day, and a 21-month study in mice at oral dosage levels of up to 30
mg/kg/day showed no evidence of carcinogenicity. There was also no mutagenic
response in vitro or in
vivo in mammalian cell assays or in
vitro in bacteria. No evidence of impaired fertility was observed
in a study performed in male and female rats at oral dosages of up to 100
mg/kg/day.<br/>Pregnancy:: Teratogenic Effects - Pregnancy Category C Reproduction
studies have been conducted in mice, rats, and rabbits. Administration of
oral doses ranging from five to ten times greater (on a mg/kg basis) than
the daily recommended oral antianginal therapeutic dose has resulted in embryo
and fetal lethality. These doses, in some studies, have been reported to cause
skeletal abnormalities. In the perinatal/postnatal studies there was some
reduction inearly individual pup weights and survival rates. There was an
increased incidence of stillbirths at doses of 20 times the human oral antianginal
dose or greater. There are no well-controlled studies
in pregnant women; therefore, use diltiazem in pregnant women only if the
potential benefit justifies the potential risk to the fetus.<br/>Nursing Mothers: Diltiazem is excreted in human milk. One report with oral
diltiazem suggests that concentrations in breast milk may approximate serum
levels. If use of diltiazem is deemed essential, an alternative method of
infant feeding should be instituted.<br/>Pediatric Use: Safety and effectiveness in pediatric patients have not been
established.<br/>Geriatric Use: Clinical studies of diltiazem did not include sufficient
numbers of subjects aged 65 and over to determine whether they respond differently
from younger subjects. Other reported clinical experience has not identified
differences in responses between the elderly and younger patients. In general,
dose selection for an elderly patient should be cautious, usually starting
at the low end of the dosing range, reflecting the greater frequency of decreased
hepatic, renal, or cardiac function, and of concomitant disease or other drug
therapy. Atrial fibrillation
or atrial flutter. In clinical studies with diltiazem HCl injection
for AF/Fl, 135 of 257 patients were over 65 years of age. No overall differences
in safety or effectiveness were observed between these patients and younger
patients, and other reported clinical experience has not identified differences
in responses between the elderly and younger patients, but greater sensitivity
of some older individuals cannot be ruled out. In subgroup analysis of double-blind
and open-label trials following first-dose response, 116 patients over 65
years of age had a response rate of 84%. One hundred two (102) patients<65
had a response rate of 78%. In subgroup analysis following a two-dose procedure
in double-blind and open-label studies, 104 patients over 65 years of age
and 95 patients<65 both had a 95% response rate. Paroxysmal supraventricular tachycardia. Clinical
studies of diltiazem hydrochloride injection for PSVT did not include sufficient
numbers of patients aged 65 and over to determine whether they respond differently
from younger patients. Other reported clinical experience has not identified
differences in responses between the elderly and younger patients. In general,
dose selection for an elderly patient should be cautious,usually starting
at the low end of the dosing range, reflecting the greater frequency of decreased
hepatic, renal, or cardiac function, and of concomitant disease or other drug
therapy. Diltiazem hydrochloride is extensively metabolized
by the liver and excreted by the kidneys and in bile. The risk of toxic reactions
to this drug may be greater in patients with impaired renal or hepatic function.
Because elderly patients are more likely to have decreased renal function,
care should betaken in dose selection, and it may be useful to monitor renal
function. As with all drugs, care should be exercised when treating patients
with multiple medications. (See PRECAUTIONS, General and Drug
Interactions.)
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Overdosage experience is limited. In the event of overdosage
or an exaggerated response, appropriate supportive measures should be employed.
The following measures may be considered: Bradycardia:Administer atropine (0.6 to 1 mg). If there is no response to vagal
blockade administer isoproterenol cautiously. High-degree AV Block: Treat as for bradycardia
above. Fixed high-degree AV block should be treated with cardiac pacing. Cardiac Failure: Administer inotropic agents (isoproterenol,
dopamine, or dobutamine) and diuretics. Hypotension:Vasopressors (e.g., dopamine or levarterenol bitartrate). The
effectiveness of intravenous calcium administration to reverse the pharmacological
effects of diltiazem overdose has been inconsistent. In a few reported cases,
overdose with calcium channel blockers associated with hypotension and bradycardia
that was initially refractory to atropine became more responsive to atropineafter the patients received intravenous calcium. In some cases intravenous
calcium has been administered (1 g calcium chloride or 3 g calcium gluconate)
over 5 minutes, and repeated every 10-20 minutes as necessary. Calcium gluconate
has also been administered as a continuous infusion at a rate of 2 g per hour
for 10 hours. Infusions of calcium for 24 hours or more may be required. Patients
should be monitored for signs of hypercalcemia. Actual
treatment and dosage should depend on the severity of the clinical situation
and the judgment and experience of the treating physician. Diltiazem does
not appear to be removed by peritoneal or hemodialysis. Limited data suggest
that plasmapheresis or charcoal hemoperfusion may hasten diltiazem elimination
following overdose. The intravenous LD's
in mice and rats were 60 and 38 mg/kg, respectively. The toxic dose in man
is not known.
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Diltiazem Hydrochloride
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Diltiazem Hydrochloride (Injection, Solution)
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The following adverse reaction rates are based on the use
of diltiazem hydrochloride injection in over 400 domestic clinical trial patients
with atrial fibrillation/flutter or PSVT under double-blind or open-label
conditions. Worldwide experience in over 1,300 patients was similar. Adverse
events reported in controlled and uncontrolled clinical trials were generally
mild and transient. Hypotension was the most commonly reported adverse event
during clinical trials. Asymptomatic hypotension occurred in 4.3% of patients.
Symptomatic hypotension occurred in 3.2% of patients. When treatment for hypotension
was required, it generally consisted of administration of saline or placing
the patient in the Trendelenburg position. Other events reported in at least
1% of the diltiazem-treated patients were injection site reactions (e.g.,
itching, burning) - 3.9%, vasodilation (flushing) - 1.7%, and arrhythmia (junctional
rhythm or isorhythmic dissociation) - 1%. In addition,
the following events were reported infrequently (less than 1%): Cardiovascular: Asystole, atrial flutter, AV block
first degree, AV block second degree, bradycardia, chest pain, congestive
heart failure, sinus pause, sinus node dysfunction, syncope, ventricular arrhythmia,
ventricular fibrillation, ventricular tachycardia. Dermatologic: Pruritus, sweating. Gastrointestinal: Constipation, elevated SGOT or
alkaline phosphatase, nausea, vomiting. Nervous
System: Dizziness, paresthesia. Other:Amblyopia, asthenia, dry mouth, dyspnea, edema, headache, hyperuricemia. Although
not observed in clinical trials with diltiazem hydrochloride injection, the
following events associated with oral diltiazem
may occur: Cardiovascular:AV block (third degree), bundle branch block, ECG abnormality,
palpitations, syncope, tachycardia, ventricular extrasystoles. Dermatologic: Alopecia, erythema multiforme (including
Stevens-Johnson syndrome, toxic epidermal necrolysis), exfoliative dermatitis,
leukocytoclastic vasculitis, petechiae, photosensitivity, purpura, rash, urticaria. Gastrointestinal: Anorexia, diarrhea, dysgeusia,
dyspepsia, mild elevations of SGPT and LDH, thirst, weight increase. Nervous System: Abnormal dreams, amnesia, depression,
extrapyramidal symptoms, gait abnormality, hallucinations, insomnia, nervousness,
personality change, somnolence, tremor. Other:Allergic reactions, angioedema (including facial or periorbitaledema), CPK elevation, epistaxis, eye irritation, gingival hyperplasia, hemolytic
anemia, hyperglycemia, impotence, increased bleeding time, leukopenia, muscle
cramps, myopathy, nasal congestion, nocturia, osteoarticular pain, polyuria,
retinopathy, sexual difficulties, thrombocytopenia, tinnitus. Events
such as myocardial infarction have been observed which are not readily distinguishable
from the natural history of the disease for the patient.
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Diltiazem hydrochloride injection is indicated for the following: The use of diltiazem hydrochloride injection should be undertaken
with caution when the patient is compromised hemodynamically or is taking
other drugs that decrease any or all of the following: peripheral resistance,
myocardial filling, myocardial contractility, or electrical impulse propagation
in the myocardium. For either
indication and particularly when employing continuous intravenous infusion,
the setting should include continuous monitoring of the ECG and frequent measurement
of blood pressure. A defibrillator and emergency equipment should be readily
available. In domestic controlled trials in
patients with atrial fibrillation or atrial flutter, bolus administration
of diltiazem hydrochloride injection was effective in reducing heart rate
by at least 20% in 95% of patients. Diltiazem hydrochloride injection rarely
converts atrial fibrillation or atrial flutter to normal sinus rhythm. Following
administration of oneor two intravenous bolus doses of diltiazem injection,
response usually occurs within 3 minutes and maximal heart rate reduction
generally occurs in 2 to 7 minutes. Heart rate reduction may last from 1 to
3 hours. If hypotension occurs, it is generally short-lived, but may last
from 1 to 3 hours. A 24-hour continuous infusion of
diltiazem injection in the treatment of atrial fibrillation or atrial flutter
maintained at least a 20% heart rate reduction during the infusion in 83%
of patients. Upon discontinuation of infusion, heart rate reduction may last
from 0.5 hours to more than 10 hours (median duration 7 hours). Hypotension,
if it occurs, may be similarly persistent. In the controlled
clinical trials, 3.2% of patients required some form of intervention (typically,
use of intravenous fluids or the Trendelenburg position) for blood pressure
support following diltiazem hydrochloride injection. In
domestic controlled trials, bolus administration of diltiazem hydrochloride
injection was effective in converting PSVT to normal sinus rhythm in 88% of
patients within 3 minutes of the first or second bolus dose. Symptoms
associated with the arrhythmia were improved in conjunction with decreased
heart rate or conversion to normal sinus rhythm following administration of
diltiazem hydrochloride injection.
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Diltiazem Hydrochloride
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