Product Elements:
Diltiazem hci diltiazem hci diltiazem hydrochloride diltiazem mannitol
Indications and Usage:
Indications & usage diltiazem hydrochloride injection or diltiazem hydrochloride for injection are indicated for the following: atrial fibrillation or atrial flutter temporary control of rapid ventricular rate in atrial fibrillation or atrial flutter. it should not be used in patients with atrial fibrillation or atrial flutter associated with an accessory bypass tract such as in wolff-parkinson-white (wpw) syndrome or short pr syndrome. in addition, diltiazem hydrochloride injection is indicated for: paroxysmal supraventricular tachycardia rapid conversion of paroxysmal supraventricular tachycardias (psvt) to sinus rhythm. this includes av nodal reentrant tachycardias and reciprocating tachycardias associated with an extranodal accessory pathway such as the wpw syndrome or short pr syndrome. unless otherwise contraindicated, appropriate vagal maneuvers should be attempted prior to administration of diltiazem hydrochloride injection. the use of diltiazem hydrochloride injection or dilti
Read more...azem hydrochloride for 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 one or two intravenous bolus doses of diltiazem hydrochloride 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 hydrochloride 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.
Warnings:
Warnings cardiac conduction. diltiazem prolongs av nodal conduction and refractoriness that may rarely result in second- or third-degree av block in sinus rhythm. concomitant use of diltiazem with agents known to affect cardiac conduction may result in additive effects (see precautions-drug interactions . if high-degree av block occurs in sinus rhythm, intravenous diltiazem should be discontinued and appropriate supportive measures instituted (see overdosage ). congestive heart failure. although diltiazem has a negative inotropic effect in isolated animal tissue preparations, hemodynamic studies in humans with normal ventricular function and in patients with a compromised myocardium, such as severe chf, acute mi, and hypertrophic cardiomyopathy, have not shown a reduction in cardiac index nor consistent negative effects on contractility (dp/dt). administration of oral diltiazem in patients with acute myocardial infarction and pulmonary congestion documented by x-ray on admission is con
Read more...traindicated. experience with the use of diltiazem hydrochloride injection in patients with impaired ventricular function is limited. caution should be exercised when using the drug in such patients. hypotension. decreases in blood pressure associated with diltiazem hydrochloride injection therapy may occasionally result in symptomatic hypotension (3.2%). the use of intravenous diltiazem for control of ventricular response in patients with supraventricular arrhythmias should be undertaken with caution when the patient is compromised hemodynamically. in addition, caution should be used in patients taking other drugs that decrease peripheral resistance, intravascular volume, myocardial contractility or conduction. acute hepatic injury. in rare instances, significant elevations in enzymes such as alkaline phosphatase, ldh, sgot, sgpt, and other phenomena consistent with acute hepatic injury have been noted following oral diltiazem. therefore, the potential for acute hepatic injury exists following administration of intravenous diltiazem. ventricular premature beats (vpbs). vpbs may be present on conversion of psvt to sinus rhythm with diltiazem hydrochloride injection. these vpbs are transient, are typically considered to be benign, and appear to have no clinical significance. similar ventricular complexes have been noted during cardioversion, other pharmacologic therapy, and during spontaneous conversion of psvt to sinus rhythm.
Dosage and Administration:
Dosage & administration 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 i
Read more...njection or diltiazem hydrochloride for injection may be administered. (for reconstitution of diltiazem hydrochloride for injection, see instructions contained within packaging.) 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 injection or diltiazem hydrochloride for injection. the recommended initial infusion rate of diltiazem hydrochloride injection or diltiazem hydrochloride for injection 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 to the desired volume of either normal saline, d5w, or d5w/0.45% nacl. mix thoroughly. keep diluted diltiazem hydrochloride injection refrigerated until use. use within 24 hours. to prepare diltiazem hydrochloride for injection for continuous intravenous infusion, assemble the add-vantage vial as directed for use with either 0.9% sodium chloride or dextrose (5%) injection. mix thoroughly. keep diluted diltiazem hydrochloride for injection at controlled room temperature 15° to 30°c (59° to 86°f) [see usp] or refrigerated 2° to 8°c (36° to 46°f) until use. use within 24 hours. dosage
Contraindications:
Contraindications injectable forms of diltiazem are contraindicated in: patients with sick sinus syndrome except in the presence of a functioning ventricular pacemaker. patients with second- or third-degree av block except in the presence of a functioning ventricular pacemaker. patients with severe hypotension or cardiogenic shock. patients who have demonstrated hypersensitivity to the drug. intravenous diltiazem and intravenous beta-blockers should not be administered together or in close proximity (within a few hours). patients with atrial fibrillation or atrial flutter associated with an accessory bypass tract such as in wpw syndrome or short pr syndrome. as with other agents which slow av nodal conduction and do not prolong the refractoriness of the accessory pathway (e.g., verapamil, digoxin), in rare instances patients in atrial fibrillation or atrial flutter associated with an accessory bypass tract may experience a potentially life-threatening increase in heart rate accompanied by hypotension when treated with injectable forms of diltiazem. as such, the initial use of injectable forms of diltiazem should be, if possible, in a setting where monitoring and resuscitation capabilities, including dc cardioversion/defibrillation, are present (see overdosage ). once familiarity of the patient's response is established, use in an office setting may be acceptable. patients with ventricular tachycardia. administration of other calcium channel blockers to patients with wide complex tachycardia (qrs ⥠0.12 seconds) has resulted in hemodynamic deterioration and ventricular fibrillation. it is important that an accurate pretreatment diagnosis distinguish wide complex qrs tachycardia of supraventricular origin from that of ventricular origin prior to administration of injectable forms of diltiazem.
Adverse Reactions:
Adverse reactions 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 f
Read more...ollowing 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: acute generalized exanthematous pustulosis, allergic reactions, angioedema (including facial or periorbital edema), cpk elevation, epistaxis, eye irritation, gingival hyperplasia, hemolytic anemia, hyperglycemia, impotence, increased bleeding time, leukopenia, muscle cramps, myopathy, nasal congestion, nocturia, osteoarticular pain, photosensitivity (including lichenoid keratosis and hyperpigmentation at sun-exposed skin areas), 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.
Overdosage:
Overdosage 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 norepinephrine). 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 atropine after 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 to 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 ld50's in mice and rats were 60 and 38 mg/kg, respectively. the toxic dose in man is not known.
Description:
Description diltiazem hydrochloride is a calcium ion cellular 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. it has a ph range of 3.7 to 4.1. diltiazem hydrochloride injection is for direct intravenous bolus injection and continuous intravenous infusion. 25-mg, 5-ml vial-each sterile vial contains 25 mg diltiazem hydrochloride, 3.75 mg citric acid usp, 3.25 mg sodium citrate dihydrate usp, 250 mg sorbitol nf and water for injection usp up to 5 ml. sodium hydroxide or hydrochloric acid is used for ph adjustment. 50-mg, 10-ml vial-each sterile vial contains 50 mg diltiazem hydrochloride, 7.5 mg citric acid usp, 6.5 mg sodium citrate dihydrate usp, 500 mg sorbitol nf and water for injection usp up to 10 ml. sodium hydroxide or hydrochloric acid is used for ph adjustment. diltiazem hydrochloride for injection is an off-white lyophilized powder and, after reconstitution in an infusion bag, produces a clear, colorless, sterile, nonpyrogenic solution. diltiazem hydrochloride for injection for continuous intravenous infusion is available in add-vantage vials. the vial contains lyophilized powder comprised of diltiazem hydrochloride 100 mg and mannitol usp 75 mg for reconstitution in the add-vantage flexible diluent container containing 5% dextrose injection or 0.9% sodium chloride injection. structure
Clinical Pharmacology:
Clinical pharmacology mechanisms of action diltiazem inhibits the influx of calcium (ca2+) 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 e
Read more...ffect on the sinus node recovery time or on the sinoatrial conduction time in patients without sa nodal dysfunction. diltiazem has no significant electrophysiologic effects 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 injection 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 emax model. 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 emax model. 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 hydrochloride is approximately 305 l. diltiazem hydrochloride 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 or 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 hydrochloride is 70% to 80% bound to plasma proteins. in vitro studies suggest alpha1âacid 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 oral clearance and prolong its half-life.
How Supplied:
How supplied diltiazem hydrochloride injection is supplied in single-dose fliptop vials as follows: diltiazem hci for injection is supplied in the following dosage forms. ndc 51662-1457-1 diltiazem hci for injection equivalent to 100mg diltiazem hci add-vantage vial ndc 51662-1457-2 diltiazem hci for injection equivalent to 100mg diltiazem hci add-vantage vial, 1 vial per pouch ndc 51662-1457-3 diltiazem hci for injection equivalent to 100mg diltiazem hci add-vantage vial, 1 vial per pouch, 10 pouches per case hf acquisition co llc, dba healthfirst mukilteo, wa 98275 diltiazem hydrochloride injection is to be stored 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. single-dose vials. discard unused portion. diltiazem hydrochloride for injection for continuous infusion is supplied in single-dose add-vantage vials as follows: diltiazem hydrochloride for injection is to be stored
Read more...at 20° to 25°c (68° to 77°f). [see usp controlled room temperature.] do not freeze. reconstituted material is stable for 24 hours at controlled room temperature or refrigerated 2° to 8°c (36° to 46°f). single-dose vial.
Package Label Principal Display Panel:
Principal display panel - vial label opt. 1 label opt. 1
Principal display panel - vial label opt. 2 vial label opt. 2
Principal display panel - serialized vial labeling serialized vial labeling
Principal display panel - ndc 51662-1547-2 pouch labeling ndc 51662-1457-2 pouch vial label pouch labeling vial label
Principal display panel- ndc 51662-1457-3 case labeling ndc 51662-1457-3 case label serialized rfid labeling case labeling serialized rfid labeling