OBJECT DRUGS

Immunosuppressants:

• Cyclosporine (Neoral, etc.)
• Everolimus (Afinitor)
• Sirolimus (Rapamune)
• Tacrolimus (Prograf, etc.)

PRECIPITANT DRUGS

Antimicrobials:

• Azithromycin (Zithromax, etc.)
• 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 antimicrobial agents may inhibit the CYP3A4 metabolism of cyclosporine, sirolimus, and tacrolimus, thus increasing their effect and potential toxicity. Inhibition of P-glycoprotein (PGP) may also contribute to the interactions. Azithromycin does not inhibit CYP3A4, but appears to inhibit PGP; it may increase plasma concentrations of these immunosuppressants by this mechanism. Clotrimazole troches have been shown to elevate tacrolimus blood levels, and would also be expected to interact with cyclosporine and sirolimus.

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 ergot alkaloids. In fact, terbinafine may slightly increase cyclosporine clearance according to the manufacturer.
• Macrolide Antibiotics: Consider using an alternative antibiotic.
• Telithromycin: Consider using an alternative antibiotic.
• Monitor: Monitor for altered immunosuppressant effect if a CYP3A4-inhibiting or PGP-inhibiting antimicrobial agent is initiated, discontinued, or changed in dosage. Substantial dosage reductions for the immunosuppressant may be needed in some cases.