OBJECT DRUGS

Opioid Analgesics:

• Alfentanil (Alfenta)
• Fentanyl (Sublimaze, etc.)
• Methadone (Dolophine, etc.)
• Oxycodone (Percocet, etc.)
• Sufentanil (Sufenta)

PRECIPITANT DRUGS

Antimicrobials:

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

Comment:

These antimicrobials inhibit CYP3A4 and may inhibit the elimination of these opioids via CYP3A4 metabolism and possibly other pathways. Excessive opioid effects have been reported. For example, voriconazole produced almost a 4-fold increase in oxycodone plasma concentrations.

Class 3: Assess Risk & Take Action if Necessary

• Consider Alternative:
• Azole Antifungals: Itraconazole and ketoconazole are potent inhibitors of CYP3A4; fluconazole appears weaker, but in larger doses it also inhibits CYP3A4. Terbinafine (Lamisil) does not appear to affect CYP3A4, and would not be expected to interact with ergot alkaloids. In fact, terbinafine may slightly increase cyclosporine clearance according to the manufacturer.
• 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 should be considered.
• Monitor: Monitor for evidence of excessive and/or prolonged opioid effects, including sedation and respiratory depression.