OBJECT DRUGS

• Irinotecan (Camptosar)

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:

CYP3A4 inhibitors may increase serum concentrations of irinotecan and its active metabolite (SN-38). Ketoconazole, for example, increased SN-38 AUC by 109%. Part of the effect of ketoconazole may be due to inhibition of the glucuronidation of SN-38 to SN-38G by UGT1A1, so it is not clear that all CYP3A4 inhibitors would necessarily interact with irinotecan. Nonetheless, the product information for irinotecan states that strong CYP3A4 inhibitors should not be used concurrently. It appears that SN-38G can be transformed back into SN-38 in the intestine by bacterial beta-glucuronidases, and be reabsorbed into the circulation. Thus, it is theoretically possible that some antibiotics could interfere with the enterohepatic circulation of irinotecan by killing these bacteria, thus tending to reduce irinotecan plasma concentrations.

Class 3: Assess Risk & Take Action if Necessary

• Consider Alternative:
• Azole Antifungals: Fluconazole is usually a weaker inhibitor of CYP3A4 unless large doses are used. Terbinafine (Lamisil) does not appear to inhibit CYP3A4.
• Macrolides: Unlike other macrolides, azithromycin (Zithromax) and dirithromycin* do not appear to inhibit CYP3A4 and would not be expected to interact with irinotecan. (*not available in US)
• Telithromycin: The use of azithromycin (Zithromax) or a quinolone antibiotic other than ciprofloxacin should be considered.