OBJECT DRUGS

• Rifabutin (Mycobutin)

PRECIPITANT DRUGS

Antimicrobials:

• 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:

Rifabutin serum concentrations can be markedly increased by CYP3A4 inhibitors; toxicity is often manifested by uveitis but rash, bone marrow suppression, and increased hepatic enzymes can also occur. Also, rifabutin may substantially reduce plasma concentrations of clarithromycin, and probably also most of the other antimicrobials listed.

Class 2: Use Only if Benefit Felt to Outweigh Risk

• Use 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 rifabutin.
• 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.
• Circumvent/Minimize: Rifabutin dose may require reduction if used with CYP3A4 inhibitors.
• Monitor: If CYP3A4 inhibitors are used with rifabutin, monitor for rifabutin toxicity, especially uveitis.