Indicated for:

Hypertension:

• The treatment of hypertension. It may be used alone or in combination with other antihypertensive medications.

Angina: 

• The management of chronic stable angina and angina due to coronary artery spasm.

Diltiazem 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 a functioning ventricular pacemaker
• Patients with hypotension (less than 90 mm Hg systolic)
• Patients who have demonstrated hypersensitivity to the drug
• Patients with acute myocardial infarction and pulmonary congestion documented by x-ray on admission

Cardiac Conduction: Diltiazem prolongs AV node refractory periods without significantly prolonging sinus node recovery time, except in patients with sick sinus syndrome. This effect may rarely result in abnormally slow heart rates (particularly in patients with sick sinus syndrome) or second- or third-degree AV block. Concomitant use of diltiazem with beta-blockers or digitalis may result in additive effects on cardiac conduction. A patient with Prinzmetal’s angina developed periods of asystole (2 to 5 seconds) after a single dose of 60 mg of diltiazem.

Congestive Heart Failure: Although diltiazem has a negative inotropic effect in isolated animal tissue preparations, hemodynamic studies in humans with normal ventricular function have not shown a reduction in cardiac index nor consistent negative effects on contractility (dP/dt). Experience with the use of diltiazem alone or in combination with beta-blockers in patients with impaired ventricular function is very limited. Caution should be exercised when using the drug in such patients.

Hypotension: Decreases in blood pressure associated with diltiazem therapy may occasionally result in symptomatic hypotension.

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. These reactions have been reversible upon discontinuation of drug therapy. The relationship to diltiazem is uncertain in most cases, but probable in some.The drug should be used with caution in patients with impaired renal or hepatic function.

Dermatological events may be transient and may disappear despite continued use of diltiazem hydrochloride. However, skin eruptions progressing to erythema multiforme and/or exfoliative dermatitis have also been infrequently reported.

Due to the potential for additive effects, caution and careful titration are warranted in patients receiving diltiazem concomitantly with any agents known to affect cardiac contractility and/or conduction.

Pharmacologic studies indicate that there may be additive effects in prolonging AV conduction when using beta-blockers or digitalis concomitantly with 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.

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.

Studies showed that diltiazem increased the AUC of midazolam and triazolam by 3- to 4-fold and the C_max by 2-fold, compared to placebo. The elimination half-life of midazolam and triazolam also increased during co-administration with diltiazem. These pharmacokinetic effects seen during diltiazem co-administration can result in increased clinical effects (e.g.,prolonged sedation) of both midazolam and triazolam.

Enhanced effects and increased toxicity of buspirone may be possible during concomitant administration with diltiazem. Subsequent dose adjustments may be necessary during coadministration, and should be based on clinical assessment.

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.

Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concurrently with diltiazem. Monitor heart rate in patients receiving concomitant diltiazem and clonidine.

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 trough dose ranging from 15% to 48% was necessary to maintain 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.

Administration of diltiazem with digoxin in 24 healthy male subjects increased plasma digoxin concentrations approximately 20%. Another investigator found no increase in digoxin levels in 12 patients with coronary artery disease. Since there have been conflicting results regarding the effect of digoxin levels, it is recommended that digoxin levels be monitored when initiating, adjusting, and discontinuing diltiazem therapy to avoid possible over- or under-digitalization.

Concurrent use of diltiazem increases exposure to ivabradine and may exacerbate bradycardia and conduction disturbances. Avoid concomitant use of ivabradine and diltiazem.

Quinidine: Diltiazem significantly increases the AUC of quinidine by 51%, T_1/2 by 36%, and decreases its CL_oral by 33%. Monitoring for quinidine adverse effects may be warranted and the dose adjusted accordingly.

Co-administration of rifampin with diltiazem lowered the diltiazem plasma concentrations to undetectable levels. Co-administration of diltiazem with rifampin or any known CYP3A4 inducer should be avoided when possible, and alternative therapy considered.Diltiazem is an inhibitor of CYP3A4 and has been shown to increase significantly the AUC of some statins. The risk of myopathy and rhabdomyolysis with statins metabolized by CYP3A4 may be increased with concomitant use of diltiazem. When possible, use a non-CYP3A4-metabolized statin together with diltiazem; otherwise, dose adjustments for both diltiazem and the statin should be considered along with close monitoring for signs and symptoms of any statin related adverse events.

Computer-based simulations showed that at a daily dose of 480 mg of diltiazem, an 8- to 9-fold mean increase in simvastatin AUC can be expected. If coadministration of simvastatin with diltiazem is required, limit the daily doses of simvastatin to 10 mg and diltiazem to 240 mg.

There are no well-controlled studies in pregnant women. Animal studies: embryo and fetal lethality and skeletal abnormalities.

Diltiazem is excreted in human milk. One report 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.

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• Use in patients under the age of 18. GoToSource

• Hypertrophic cardiomyopathy. GoToSource

• Anal fissures (topical formulation), migraine prophylaxis, cramps in lower leg related to rest and pulmonary hypertension. GoToSource

• Adjunctive therapy for idiopathic dilated cardiomyopathy. GoToSource

• Adjunctive therapy for prostate cancer. GoToSource

• Capecitabine-induced chest pain. GoToSource

• Diabetic nephropathy. GoToSource

Peripheral edema (accumulation of fluid causing swelling in tissues). GoToSource

Increased risk of myocardial infarction. GoToSource

Cardiac conduction defects. GoToSource

Palpitations, hypotension (low blood pressure), hypersensitivity reactions and stevens johnson syndrome (severe drug reaction). GoToSource

Congestive heart failure, bradycardia (slow heart rate), hepatotoxicity (liver damage) and hyperglycemia (high blood sugar). GoToSource

Myoclonus (involuntary muscle jerk). GoToSource

Hyperpigmentation (excess pigmentation). GoToSource

Paralytic ileus (obstruction from paralysis of intestinal muscles). GoToSource.

Exacerbation of lambert-eaton myasthenic syndrome. GoToSource

Lawsuits filed for permanent male infertility.