Mibefradil dihydrochloride, a nondihydropyridine calcium channel blocker, has been approved by the U.S. Food and Drug Administration for the treatment of hypertension and chronic stable angina. This agent is the first T-type (transient) calcium channel blocker. Consultants for The Medical Letter on Drugs and Therapeutics reviewed the available data on this new drug.
All of the currently available calcium channel blockers prevent calcium influx in L-type (long-acting) channels throughout the vascular system and myocardium. Mibefradil also blocks T-type calcium channels, which are activated at lower voltages and are found in vascular smooth muscle and the myocardial conduction system but not in the ventricular myocardium. Mibefradil produces coronary and peripheral vasodilation without reflex tachycardia. It is not known whether mibefradil's T-type calcium channel activity offers any advantage over older calcium channel blockers.
Studies comparing the antihypertensive effects of mibefradil with those of other calcium channel blockers indicated that mibefradil was more effective in blood pressure reduction than diltiazem and about as effective as amlodipine and nifedipine. In one study, the addition of an angiotensin converting enzyme inhibitor to mibefradil therapy was found to increase the antihypertensive effect.
Two controlled studies of the use of mibefradil in chronic stable angina demonstrated that this agent was more effective than placebo in delaying the onset of ischemia during exercise and in increasing exercise tolerance. A large trial of the use of mebefradil in patients with congestive heart failure is currently under way.
Like other calcium channel blockers, mibefradil causes a slight decrease in heart rate. Sinus bradycardia, first-degree atrioventricular block and asymptomatic Wencke-bach-type block can occur with use of mibefradil. Third-degree block has not been reported when the drug is taken at recommended dosages; however, higher dosages have been associated with QT changes.
Patients with sick sinus syndrome or second- or third-degree atrioventricular block without a pacemaker should not take mibefradil. This drug should not be used in patients taking terfenadine, astemizole or cisapride because of the risk of fatal arrhythmias if plasma concentrations increase. Syncope has been noted with mibefradil, particularly in elderly patients who are also receiving a beta blocker. Plasma levels of tricyclic antidepressants and cyclosporine can increase with concomitant administration of mibefradil, and dosage adjustment may be necessary.
Side effects reported with mibefradil include dizziness, fatigue and lightheadedness. In studies comparing mibefradil with other calcium channel blockers, peripheral edema has occurred less frequently with use of mibefradil than with diltiazem, nifedipine and amlodipine.
The recommended starting dosage of mibefradil in the treatment of patients with either hypertension or chronic stable angina is 50 mg daily, which can be increased to 100 mg once daily. Mibefradil should be used cautiously in patients with liver dysfunction.