Diltiazem Hydrochloride (13 brand names, 5 dosage forms, 3 routes)
Available dosage forms: TABLET, CAPSULE, EXTENDED RELEASE, TABLET, EXTENDED RELEASE, INJECTABLE, SOLUTION.
Routes of administration: ORAL, INJECTION, INTRAVENOUS.
Brand Names
- CARDIZEM
- CARDIZEM CD
- CARDIZEM LA
- CARDIZEM SR
- CARTIA XT
- DILACOR XR
- DILT-CD
- DILTIAZEM HYDROCHLORIDE
- DILTIAZEM HYDROCHLORIDE IN 0.72% SODIUM CHLORIDE
- DILTIAZEM HYDROCHLORIDE IN DEXTROSE 5%
- DILTZAC
- TAZTIA XT
- TIAZAC
Indications and Usage
Diltiazem hydrochloride extended-release capsules, USP (once-a-day dosage) are indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive medications. Diltiazem hydrochloride extended-release capsules, USP (once-a-day dosage) are indicated for the management of chronic stable angina and angina due to coronary artery spasm.
Dosage and Administration
Patients controlled on diltiazem alone or in combination with other medications may be switched to diltiazem hydrochloride extended-release capsules, USP (once-a-day dosage) at the nearest equivalent total daily dose. Higher doses of diltiazem hydrochloride extended-release capsules, USP (once-a-day dosage) may be needed in some patients. Monitor patients closely. Subsequent titration to higher or lower doses may be necessary. There is limited general clinical experience with doses above 360 mg, but doses to 540 mg have been studied in clinical trials. The incidence of side effects increases as the dose increases with first-degree AV block, dizziness, and sinus bradycardia bearing the strongest relationship to dose. Hypertension:Adjust dosage to individual patient needs. When used as monotherapy, reasonable starting doses are 180 mg to 240 mg once daily, although some patients may respond to lower doses. Maximum antihypertensive effect is usually observed by 14 days of chronic therapy; therefore, schedule dosage adjustments accordingly. The usual dosage range studied in clinical trials was 240 mg to 360 mg once daily. Individual patients may respond to higher doses of up to 480 mg once daily. Angina:Dosages for the treatment of angina should be adjusted to each patient’s needs, starting with a dose of 120 or 180 mg once daily. Individual patients may respond to higher doses of up to 480 mg once daily. When necessary, titration may be carried out over a 7- to 14-day period. Concomitant Use with Other Cardiovascular Agents: Sublingual NTG:May be taken as required to abort acute anginal attacks during diltiazem hydrochloride therapy. Prophylactic Nitrate Therapy:Diltiazem hydrochloride may be safely coadministered with short- and long-acting nitrates. Beta-blockers: [See Warnings and Precautions.] Antihypertensives:Diltiazem hydrochloride have an additive antihypertensive effect when used with other antihypertensive agents. Therefore, the dosage of diltiazem hydrochlor
Contraindications
Diltiazem hydrochloride extended-release capsules are contraindicated in (1) patients with sick sinus syndrome except in the presence of a functioning ventricular pacemaker, (2) patients with second- or third-degree AV block except in the presence of a functioning ventricular pacemaker, (3) patients with hypotension (less than 90 mm Hg systolic), (4) patients who have demonstrated hypersensitivity to the drug, and (5) patients with acute myocardial infarction and pulmonary congestion documented by x-ray on admission.
Adverse Reactions
Serious adverse reactions have been rare in studies carried out to date, but it should be recognized that patients with impaired ventricular function and cardiac conduction abnormalities have usually been excluded from these studies. The following table presents the most common adverse reactions reported in placebo-controlled angina and hypertension trials in patients receiving diltiazem hydrochloride extended-release capsules up to 360 mg with rates in placebo patients shown for comparison. Diltiazem Hydrochloride Extended-Release CapsulesPlacebo-Controlled Angina and Hypertension Trials Combined Adverse Reactions Diltiazem Hydrochloride Extended-Release Capsules (n=607) Placebo ( n=301) Headache 5.4 % 5.0 % Dizziness 3.0 % 3.0% Bradycardia 3.3 % 1.3% AV Block First Degree 3.3 % 0.0% Edema 2.6 % 1.3% Asthenia 1.8 % 1.7% In addition, the following events were reported infrequently (less than 1%) in angina or hypertension trials: Cardiovascular:Congestive heart failure, palpitations, syncope, ventricular extrasystoles. Nervous System:Abnormal dreams, amnesia, depression, gait abnormality, hallucinations, insomnia, nervousness, paresthesia, personality change, somnolence, tinnitus, tremor. Gastrointestinal:Anorexia, constipation, diarrhea, dry mouth, dysgeusia, dyspepsia, mild elevations of SGOT, SGPT, LDH, and alkaline phosphatase [ see Warnings, Acute Hepatic Injury], thirst, vomiting, weight increase. Dermatological:Petechiae, photosensitivity, pruritus, urticaria. Other:Amblyopia, CPK increase, dyspnea, epistaxis, eye irritation, hyperglycemia, hyperuricemia, impotence, muscle cramps, nasal congestion, nocturia, osteoarticular pain, polyuria, sexual difficulties. The following postmarketing events have been reported infrequently in patients receiving diltiazem hydrochloride: acute generalized exanthematous pustulosis, allergic reactions, alopecia, angioedema (including facial or periorbital edema), asystole, erythema multiforme (including Stevens-Johnson syndrome,
Overdosage
The oral LD 50sin mice and rats range from 415 to 740 mg/kg and from 560 to 810 mg/kg, respectively. The intravenous LD 50sin these species were 60 and 38 mg/kg, respectively. The oral LD 50in dogs is considered to be in excess of 50 mg/kg, while lethality was seen in monkeys at 360 mg/kg. The toxic dose in man is not known. Because of its extensive metabolism, blood levels after a standard dose of diltiazem can vary over tenfold, limiting the usefulness of blood levels in overdose cases. There have been reports of diltiazem overdose in amounts ranging from <1 g to 18 g. Of cases with known outcome, most patients recovered and in cases with a fatal outcome, the majority involved multiple drug ingestion. Events observed following diltiazem overdose included bradycardia, hypotension, heart block, and cardiac failure. Most reports of overdose described some supportive medical measure and/or drug treatment. Bradycardia frequently responded favorably to atropine, as did heart block, although cardiac pacing was also frequently utilized to treat heart block. Fluids and vasopressors were used to maintain blood pressure and in cases of cardiac failure, inotropic agents were administered. In addition, some patients received treatment with ventilatory support, gastric lavage, activated charcoal, and/or intravenous calcium. In the event of overdose or exaggerated response, appropriate supportive measures should be employed in addition to gastrointestinal decontamination. 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. Based on the known pharmacological effects of diltiazem and/or reported clinical experiences, the following measures may be considered: Bradycardia:Administer atropine (0.60 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