OBJECT DRUGS

• Colchicine (Colcrys)

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 CYP3A4 and P-glycoprotein (P-gp) and concurrent use of CYP3A4 and P-gp 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. Most of the antimicrobials above inhibit both CYP3A4 and P-gp, and it has not been established that drugs inhibiting only one or the other would increase colchicine plasma levels. For example, voriconazole inhibits CYP3A4 but may not have much effect on P-gp, so it is possible that it is less likely to interact with colchicine than drugs that inhibit both.

Class 2: Use Only if Benefit Felt to Outweigh Risk

• Use Alternative: Colchicine toxicity can be fatal, and few situations warrant the use of a CYP3A4/PGP 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.
• Telithromycin: The use of azithromycin (Zithromax) or a quinolone antibiotic other than ciprofloxacin should be considered.
• 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.