Drug interactions between clarithromycin and Isoptin

MONITOR: Coadministration with certain macrolide antibiotics may increase the plasma concentrations and pharmacologic effects of verapamil. The proposed mechanism is macrolide inhibition of CYP450 3A4, the isoenzyme responsible for hepatic first-pass and systemic metabolic clearance of verapamil. Macrolides that may significantly inhibit CYP450 3A4 include clarithromycin, erythromycin, and troleandomycin. Azithromycin and dirithromycin are generally believed to have little, if any, effect on CYP450 3A4. Clinically, the interaction is supported by isolated case reports of elderly patients stabilized on verapamil and other medications who developed symptoms of verapamil toxicity (e.g., hypotension, bradycardia, atrioventricular block) within 2 to 7 days after initiation of erythromycin or clarithromycin therapy. One of the patients also had QT interval prolongation, which may be induced by elevated levels of erythromycin secondary to inhibition of intestinal P-glycoprotein and CYP450 3A4 by verapamil. The interaction was also suspected in a 53-year-old woman who was started on verapamil and clarithromycin concurrently and developed bradycardia, dizziness, hypotension and fainting after 24 hours. In all cases, discontinuation or dosage reduction of verapamil in addition to supportive care led to resolution of symptoms.

MANAGEMENT: Caution is advised if verapamil must be used with clarithromycin, erythromycin or troleandomycin, particularly in susceptible patients such as the elderly or debilitated. Cardiac function and pharmacologic response to verapamil should be monitored more closely whenever the macrolide antibiotic is added to or withdrawn from therapy in patients stabilized on their verapamil regimen, and the dosage adjusted as necessary. Azithromycin and dirithromycin may be safer alternatives during therapy with verapamil.