OBJECT DRUGS

Carbamazepine (Tegretol, etc.)

PRECIPITANT DRUGS

Antimicrobials:

• Ciprofloxacin (Cipro, etc.)
• Clarithromycin (Biaxin, etc.)
• Erythromycin (E-Mycin, etc.)
• Fluconazole (Diflucan)
• Itraconazole (Sporanox, etc.)
• Ketoconazole (Nizoral, etc.)
• Posaconazole (Noxafil)
• Quinupristin (Synercid)
• Telithromycin (Ketek)
• Troleandomycin (TAO)
• Voriconazole (Vfend)

Comment:

Inhibition of CYP3A4 (and possibly other enzymes) by these antimicrobials 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. Metronidazole (Flagyl) has also been reported to cause carbamazepine toxicity in isolated cases, but more study is needed.

Class 3: Assess Risk & Take Action if Necessary

• Consider Alternative:
• Azole Antifungals: Fluconazole appears to be a less potent inhibitor of CYP3A4; but in larger doses it also inhibits CYP3A4. Terbinafine (Lamisil) does not appear to affect CYP3A4.
• Macrolide Antibiotics: Unlike erythromycin, clarithromycin and troleandomycin, Azithromycin (Zithromax) and dirithromycin* do not appear to inhibit CYP3A4 (*not available in US)
• Telithromycin: The use of azithromycin (Zithromax) or a quinolone antibiotic other than ciprofloxacin should be considered.
• Monitor: If alternatives are not appropriate, consider reducing carbamazepine dose. Monitor for altered carbamazepine effect if enzyme inhibitors are started, stopped or changed in dosage. Symptoms of carbamazepine toxicity include nausea, vomiting, dizziness, drowsiness, headache, diplopia, and confusion.