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 other pathways. Excessive opioid effects have been reported. For example, voriconazole produced almost a 4-fold increase in oxycodone plasma concentrations. Methadone is primarily metabolized by CYP2B6 and will be affected by inhibitors of this enzyme [clopidogrel (Plavix), cyclophosphamide (Cytoxan), ticlopidine (Ticlid) ].

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.
• 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: Monitor for evidence of excessive and/or prolonged opioid effects, including sedation and respiratory depression.