Diltiazem Taj Pharma hydrochloride injection is a calcium ion influx inhibitor (slow channel blocker or calcium channel antagonist). Chemically Diltiazem Taj Pharma hydrochloride is 1, 5-benzothiazepin-4(5H) one,3-(acetyloxy)- 5-[2-(dimethylamino) ethyl]-2, 3-dihydro-2-(4-methoxyphenyl)-, monohydrochloride, (+)-cis-.
The molecular formula is C H N O S•HCl
It has a molecular weight of 450.99.
Diltiazem Taj Pharma hydrochloride injection is a clear, colorless, sterile, nonpyrogenic solution. It has a pH range of 3.7 to 4.1. Diltiazem Taj Pharma hydrochloride injection is for direct intravenous bolus injection and continuous intravenous infusion.
Name of medicinal products
Diltiazem Hydrochloride Injection USP 25mg/5ml-Taj Pharma
Diltiazem Hydrochloride Injection USP 50mg/10ml-Taj Pharma
Diltiazem Hydrochloride Injection USP 125mg/25ml-Taj Pharma
2. Qualitative and quantitative composition
a) Diltiazem Hydrochloride Injection USP 25mg/5ml-Taj Pharma
Each 5ml contains:
Diltiazem Hydrochloride USP 25mg
b) Diltiazem Hydrochloride Injection USP 50mg/10ml-Taj Pharma
Each 10ml contains:
Diltiazem Hydrochloride USP 50mg
c) Diltiazem Hydrochloride Injection USP 125mg/25ml-Taj Pharma
Each 25ml contains:
Diltiazem Hydrochloride USP 125mg
3. Pharmaceutical form
Diltiazem Taj Pharma hydrochloride is a white to off-white crystalline powder with a bitter taste. It is soluble in water, methanol, and chloroform.
4. Clinical Pharmacology
Mechanisms of Action
Diltiazem Taj Pharma inhibits the influx of calcium (Ca ) ions during membrane depolarization of cardiac and vascular smooth muscle. The therapeutic benefits of Diltiazem Taj Pharma in supraventricular tachycardias are related to its ability to slow AV nodal conduction time and prolong AV nodal refractoriness. Diltiazem Taj Pharma 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 Taj Pharma slows the ventricular rate in patients with a rapid ventricular response during atrial fibrillation or atrial flutter. Diltiazem Taj Pharma converts paroxysmal supraventricular tachycardia (PSVT) to normal sinus rhythm by interrupting the reentry circuit in AV nodal reentrant tachycardias and reciprocating tachycardias, eg, Wolff-Parkinson-White syndrome (WPW).
Diltiazem Taj Pharma 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 Taj Pharma has no significant electrophysiologic effects on tissues in the heart that are fast sodium channel dependent, eg, HisPurkinje tissue, atrial and ventricular muscle, and extranodal accessory pathways.
Like other calcium antagonists, because of its effect on vascular smooth muscle, Diltiazem Taj Pharma decreases total peripheral resistance resulting in a decrease in both systolic and diastolic blood pressure.
In patients with cardiovascular disease, Diltiazem Taj Pharma 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 Taj Pharma 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 pre-existing impaired ventricular function.
The prolongation of PR interval correlated significantly with plasma Diltiazem Taj Pharma concentration in normal volunteers using the Sigmoidal E model. Changes in heart rate, systolic blood pressure, and diastolic blood pressure did not correlate with Diltiazem Taj Pharma plasma concentration in normal volunteers.
Reduction in mean arterial pressure correlated linearly with Diltiazem Taj Pharma 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 Taj Pharma concentration using the Signmoidal E model. Based on this relationship, the mean plasma Diltiazem Taj Pharma concentration required to produce a 20% decrease in heart rate was determined to be 80 ng/mL. Mean plasma Diltiazem Taj Pharma concentrations of 130 ng/mL and 300 ng/mL were determined to produce reductions in heart rate of 30% to 40%.
Pharmacokinetics and Metabolism
Following a single intravenous injection in healthy male volunteers, Diltiazem Taj Pharma 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 Taj Pharma hydrochloride is approximately 305 L. Diltiazem Taj Pharma 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 Taj Pharma 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 Taj Pharma 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 10mg/h or 15 mg/h for 24 hours, Diltiazem Taj Pharma 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 Taj Pharma hydrochloride formulations, constant rate intravenous infusions of Diltiazem Taj Pharma hydrochloride at 3, 5, 7, and 11 mg/h are predicted to produce steady-state plasma Diltiazem Taj Pharma concentrations equivalent to 120-, 180-, 240-, and 360-mg total daily oral doses of Diltiazem Taj Pharma hydrochloride tablets or capsules.
After oral administration, Diltiazem Taj Pharma hydrochloride 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 Taj Pharma, desacetylDiltiazem Taj Pharma, desacetyl-NmonodesmethylDiltiazem Taj Pharma, desacetyl-O-desmethylDiltiazem Taj Pharma, and desacetyl-N, O-desmethylDiltiazem Taj Pharma have been identified in human urine. Following oral administration, 2% to 4% of the unchanged Diltiazem Taj Pharma appears in the urine. Drugs which induce or inhibit hepatic microsomal enzymes may alter Diltiazem Taj Pharma max max disposition.
Following single intravenous injection of Diltiazem Taj Pharma hydrochloride, however, plasma concentrations of
N-monodesmethylDiltiazem Taj Pharma and desacetylDiltiazem Taj Pharma, 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 Taj Pharma and are more slowly eliminated; half-life of total radioactivity is about 20 hours compared to 2 to 5 hours for Diltiazem Taj Pharma.
Diltiazem Taj Pharma hydrochloride 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 Taj Pharma 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 Taj Pharma disposition following oral administration. Liver cirrhosis was shown to reduce Diltiazem Taj Pharma’s apparent oral clearance and prolong its half-life.
Inication and uses
Diltiazem Taj Pharma hydrochloride injection is 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.
- 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 Taj Pharma hydrochloride injection.
The use of Diltiazem Taj Pharma hydrochloride injection for control of ventricular response in patients with atrial fibrillation or atrial flutter or conversion to sinus rhythm in patients with PSVT 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, orelectrical impulse propagation in the myocardium.
For either indication and particularly when employing continuous intravenous infusion, the s etting 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 Taj Pharma hydrochloride injection was effective in reducing heart rate by at least 20% in 95% of patients. Diltiazem Taj Pharma hydrochloride injection rarely converts atrial fibrillation or atrial flutter to normal sinus rhythm. Following administration of one or two intravenous bolus doses of Diltiazem Taj Pharma 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 Taj Pharma 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 Taj Pharma hydrochloride injection.
In domestic controlled trials, bolus administration of Diltiazem Taj Pharma 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 Taj Pharma hydrochloride injection.
Diltiazem Taj Pharma hydrochloride injection is 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 functioning ventricular pacemaker.
- Patients with severe hypotension or cardiogenic shock.
- Patients who have demonstrated hypersensitivity to the drug.
- Intravenous Diltiazem Taj Pharma 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 (eg, 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 Diltiazem Taj Pharma hydrochloride injection. As such, the initial use of Diltiazem Taj Pharma hydrochloride injection 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 Diltiazem Taj Pharma hydrochloride injection.
- Cardiac Conduction. Diltiazem Taj Pharma prolongs AV nodal conduction and refractoriness that may rarely result in second- or third-degree AV block or sinus rhythm. Concomitant use of Diltiazem Taj Pharma 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 Taj Pharma should be discontinued and appropriate supportive measures instituted (see OVERDOSAGE).
- Congestive Heart Failure. Although Diltiazem Taj Pharma has a negative inotropic effect in isolated animal tissue preparations, hemodynamic studies in humans with normal ventricular function and in patientswith 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 Taj Pharma in patients with acute myocardial infarction and pulmonary congestion documented by x-ray on admission is contraindicated. Experience with the use of Diltiazem Taj Pharma hydrochloride injection in patients with impaired ventricular function is limited. Caution should be exercised when using the drug in such patients.
- Decreases in blood pressure associated with Diltiazem Taj Pharma hydrochloride injection therapy may occasionally result in symptomatic hypotension (3.2%). The use of intravenous Diltiazem Taj Pharma 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 Taj Pharma. Therefore, the potential for acute hepatic injury exists following administration of intravenous Diltiazem Taj Pharma.
- Ventricular Premature Beats (VPBs). VPBs may be present on conversion of PSVT to sinus rhythm with Diltiazem Taj Pharma 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.
Diltiazem Taj Pharma 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 Taj Pharma 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 Taj Pharma. Therefore, the potential for these dermatologic reactions exists following exposure to intravenous Diltiazem Taj Pharma. Should a dermatologic reaction persist, the drug should be discontinued.
Due to potential for additive effects, caution is warranted in patients receiving Diltiazem Taj Pharma hydrochloride injection concomitantly with other agent(s) known to affect cardiac contractility and/or SA or AV node conduction (see WARNINGS).
As with all drugs, care should be exercised when treating patients with multiple medications. Diltiazem Taj Pharma hydrochloride undergoes extensive metabolism by the cytochrome P-450 mixed function oxidase system. Although specific pharmacokinetic drug-drug interaction studies have not been conducted with single intravenous injection or constant rate intravenous infusion, coadministration of Diltiazem Taj Pharma hydrochloride injection with other agents which primarily undergo the same route of biotransformation may result in competitive inhibition of metabolism.
Digitalis. Intravenous Diltiazem Taj Pharma 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 excessiveslowing of the heart rate and/or AV block.
Beta-blockers. Intravenous Diltiazem Taj Pharma 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 Taj Pharma is administered to patients receiving chronic oral beta-blocker therapy, the possibility for bradycardia, AV block, and/or depression of contractility should be considered (seeCONTRAINDICATIONS). Oral administration of Diltiazem Taj Pharma with propranolol in five normalvolunteers 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 Taj Pharma.
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.
Cyclosporine. A pharmacokinetic interaction between Diltiazem Taj Pharma 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 Taj Pharma. If these agents are to be administered concurrently, cyclosporine concentrations should be monitored, especially when Diltiazem Taj Pharma therapy is initiated, adjusted or discontinued.
The effect of cyclosporine on Diltiazem Taj Pharma plasma concentrations has not been evaluated.
Carbamazepine. Concomitant administration of oral Diltiazem Taj Pharma 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.
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.
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 in early 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 Taj Pharma hydrochloride injection in pregnant women only if the potential benefit justifies the potential risk to the fetus.
Diltiazem Taj Pharma is excreted in human milk. One report with oral Diltiazem Taj Pharma suggests that concentrations in breast milk may approximate serum levels. If use of Diltiazem Taj Pharma is deemed essential, an alternative method of infant feeding should be instituted.
Safety and effectiveness in pediatric patients have not been established.
The following adverse reaction rates are based on the use of Diltiazem Taj Pharma hydrochloride injection in over 400 domestic clinical trial patients with atrial fibrillation/flutter or PSVT under double-blind or openlabel conditions. Worldwide experience in over 1300 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 Taj Pharma-treated patients were injection site reactions (eg, itching, burning) – 3.9%, vasodilation (flushing) -1.7%, and arrhythmia (junctional rhythm or isorhythmic dissociation) – 1.0%.
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 Taj Pharma hydrochloride injection, the following events associated with oral Diltiazem Taj Pharma may occur: Cardiovas cular: 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 periorbital edema), CPK elevation, epistaxis, eye irritation, gingival hyperplasia, hemolytic anemia, hyperglycemia, impotence, increased bleeding time, leukopenia, muscle cramps, 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.
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 1.0 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 (eg, dopamine or levarterenol bitartrate).
Actual treatment and dosage should depend on the severity of the clinical situation and the judgment and experience of the treating physician. Diltiazem Taj Pharma does not appear to be removed by peritoneal or hemodialysis. Limited data suggest that plasmapheresis or charcoal hemoperfusion may hasten Diltiazem Taj Pharma elimination following overdose.
The intravenous LD’s in mice and rats were 60 to 38 mg/kg, respectively. The toxic dose in man is not known.
5. Dosage and Administration
Direct Intravenous Single Injections (Bolus)
The initial dose of Diltiazem Taj Pharma 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 Taj Pharma 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 Taj Pharma hydrochloride injection may be administered. Immediately following bolus administration of 20 mg (0.25 mg/kg) or 25 mg (0.35 mg/kg) Diltiazem Taj Pharma hydrochloride injection and reduction of heart rate, begin an intravenous infusion of Diltiazem Taj Pharma hydrochloride injection.
The recommended initial infusion rate of Diltiazem Taj Pharma hydrochloride 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 Taj Pharma 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 Taj Pharma hydrochloride injection for continuous intravenous infusion aseptically transfer the appropriate quantity (see chart) of Diltiazem Taj Pharma 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.
Diltiazem Taj Pharma Hydrochloride
Injection to Add
|100 mL||125 mg (25 mL)||1 mg/mL||10 mg/h 15 mg/h||10 mL/h 15 mL/h|
|250 mL||250 mg (50 mL)||0.83 mg/mL||10 mg/h 15 mg/h||12 mL/h 18 mL/h|
|500 mL||250 mg (50 mL)||0.45 mg/mL||10 mg/h 15 mg/h||22 mL/h 33 mL/h|
Diltiazem Taj Pharma hydrochloride injection was tested for compatibility with three commonly used intravenous fluids at a maximal concentration of 1 mg Diltiazem Taj Pharma hydrochloride per milliliter. Diltiazem Taj Pharma 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 15° to 30°C (59° to 86°F) 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
Because of potential physical incompatibilities, it is recommended that Diltiazem Taj Pharma hydrochloride injection not be mixed with any other drugs in the same container.
If possible, it is recommended that Diltiazem Taj Pharma hydrochloride injection not be co-infused in the same intravenous line. Physical incompatibilities (precipitate formation or cloudiness) were observed when Diltiazem Taj Pharma hydrochloride injection 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.
Parental drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Transition to Further Antiarrhythmic Therapy
Transition to other antiarrhythmic agents following administration of Diltiazem Taj Pharma 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 Taj Pharma hydrochloride injection. These antiarrhythmic agents were intravenous or oral digoxin, Class I antiarrhythmics (eg, quinidine, procainamide), calcium channel blockers, and oral beta-blockers.
Experience in the use of antiarrhythmic agents following maintenance infusion of Diltiazem Taj Pharma hydrochloride injection is limited. Patients should be dosed on an individual basis and reference should be made to respective manufacturer’s package insert for information relative to dosage and administration.
Diltiazem Taj Pharma Hydrochloride Injection 25mg/5ml, 50mg/10ml,125mg/25ml are supplied:
SINGLE-DOSE CONTAINERS. DISCARD UNUSED PORTION.
Storage: Store 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.
Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Unit No. 214.Old Bake House,
Maharashtra chambers of Commerce Lane,
Fort, Mumbai – 400001
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)Monday through Saturday 9:00 a.m. to 7:00 p.m. EST E-mail: firstname.lastname@example.org