The safety and tolerability of
mibefradil, a selective
T-type calcium channel antagonist, were evaluated in 3,430 patients with
essential hypertension and
chronic stable angina pectoris treated in 15 double-blind placebo and active-controlled clinical trials and 2 open-label, long-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 placebo-treated patients. Treatment with the 100-mg dose was associated with 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
lightheadedness (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 better tolerated than
amlodipine and
nifedipine SR/GITS and was as well tolerated 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
atrioventricular block were the only relevant treatment-emergent electrocardiographic changes that occurred more frequently with
mibefradil than with placebo. No evidence of first-dose effects was observed in
mibefradil-treated patients, and withdrawal effects were not observed in clinical trials. There were no clinically important differences in safety 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.