SAFETY OF MIBEFRADIL, A NEW ONCE-A-DAY, SELECTIVE T-TYPE CALCIUM-CHANNEL ANTAGONIST

The safety and tolerability of mibefradil, a selective T-type calcium channel antagonist, were evaluated in 3,430 patients with essential hy pertension and chronic stable angina pectoris treated in 15 double-bli nd placebo and active-controlled clinical trials and 2 open-label, lon g-term safety studies. Of these patients, 2,636 were treated with the recommended doses of mibefradil (50 and 100 mg) and form the basis of this report. With the 50-mg dose of mibefradil, the incidence of each adverse event was similar to, or lower than, that observed in the plac ebo-treated patients. Treatment with the 100-mg dose was associated wi th a slightly higher incidence compared to placebo of dizziness (2.1% vs 1.8%), leg edema (3.5% vs 1.4%), fatigue (2.1% vs 1.4%), and lighth eadedness (2.1% vs 0.4%). The incidence of headache (4.6%) and angina pectoris (1.1%) was more frequent in patients treated with placebo. In active-controlled trials, a lower incidence of pedal edema (5.1%) was observed with mibefradil compared to amlodipine (25.7%), diltiazem SR /CD (9.4%), or nifedipine SR/GITS (17.4%). Overall, mibefradil was bet ter tolerated than amlodipine and nifedipine SR/GITS and was as well t olerated as diltiazem SR/CD. Rates of premature discontinuation due to clinically adverse experiences with the 50- and 100-mg doses were 2.5 % and 3.5%, respectively, compared with placebo (3.5%). No consistent pattern of laboratory adverse experiences were observed for mibefradil . Sinus bradycardia (heart rate <45 beats/minute) and first-degree atr ioventricular block were the only relevant treatment-emergent electroc ardiographic changes that occurred more frequently with mibefradil tha n with placebo. No evidence of first-dose effects was observed in mibe fradil-treated patients, and withdrawal effects were not observed in c linical trials. There were no clinically important differences in safe ty profiles in the demographic subgroups for age, gender, or race. The results of this comprehensive safety analysis indicate that treatment with the recommended doses of mibefradil is well tolerated and safe. (C) 1997 by Excerpta Medica, Inc.