OBJECT DRUGS

• Carbamazepine (Tegretol, etc.)

PRECIPITANT DRUGS

Calcium Channel Blockers:

• Diltiazem (Cardizem, etc.)
• Verapamil (Isoptin, etc.)

Comment:

Inhibition of CYP3A4 by these calcium channel blockers may result in carbamazepine toxicity, usually within 2-3 days of starting the inhibitor. Adverse outcomes from these interactions are fairly predictable, and most patients who start a CYP3A4 inhibitor while on carbamazepine will develop clinical evidence of carbamazepine toxicity. Keep in mind also that enzyme inducers such as carbamazepine can markedly reduce plasma concentrations of most calcium channel blockers.

Class 3: Assess Risk & Take Action if Necessary

• Consider Alternative: Diltiazem, verapamil, and possibly nicardipine are the only calcium channel blockers (CCBs) known to inhibit CYP3A4; other CCBs are probably less likely to cause carbamazepine toxicity.
• Monitor: If alternatives are not appropriate, consider reducing the dose of carbamazepine. Monitor for altered carbamazepine effect if enzyme inhibitors are initiated, discontinued, or changed in dosage. Symptoms of carbamazepine toxicity include nausea, vomiting, dizziness, drowsiness, headache, diplopia, and confusion.