OBJECT DRUGS

Vinca Alkaloids:

• Vinblastine (Velban)
• Vincristine (Oncovin)
• Vinorelbine (Navelbine)

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:

Vinca alkaloids appear to be metabolized by CYP3A4, and reports have described severe toxicity in patients receiving concurrent therapy with CYP3A4 inhibitors. Assume that all CYP3A4 inhibitors interact until proved otherwise. P-glycoprotein inhibition may also be involved in these interactions.

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 vinca alkaloids.
• 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 toxicity from vincristine (primarily peripheral neuropathy symptoms: paresthesias, neuritic pain, muscle pain, constipation sometimes progressing to paralytic ileus) or vinblastine and vinorelbine (primarily bone marrow suppression).