OBJECT DRUGS
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:
Colchicine is a substrate for P-glycoprotein (PGP) and concurrent use of PGP inhibitors has resulted in severe colchicine toxicity, including gastrointestinal toxicity, rhabdomyolysis, pancytopenia, and multi-organ failure. Colchicine toxicity is difficult to treat, and fatalities have been reported. Colchicine is also a substrate for CYP3A4 and inhibitors of this enzyme may also increase its plasma concentrations.
Class 2: Use Only if Benefit Felt to Outweigh Risk
- Use Alternative: Given the possibility of fatal colchicine toxicity, few situations would warrant the use of a PGP or CYP3A4 inhibitor with colchicine. Select an alternative that is not known to inhibit PGP or CYP3A4, especially if the patient has renal impairment.
- Azole Antifungals: Terbinafine (Lamisil) does not appear to affect CYP3A4, and is not known to inhibit P-glycoprotein, but monitor for colchicine toxicity if it is used.
- Macrolide Antibiotics: Unlike erythromycin, clarithromycin and troleandomycin, azithromycin (Zithromax) does not appear to inhibit CYP3A4. But it may weakly inhibit P-glycoprotein, so monitor for colchicine toxicity if it is used.
- Monitor: If the combination must be used, monitor carefully for toxicity from colchicine including diarrhea, fever, abdominal pain, muscle pain or weakness, and paresthesias. Discontinue both drugs immediately if toxicity is suspected.