OBJECT DRUGS

Antiarrhythmics (CYP3A4 Substrates):

• Amiodarone (Cordarone, etc.)
• Disopyramide (Norpace, etc.)
• Dronedarone (Multaq)
• Quinidine (Quinidex)

PRECIPITANT DRUGS

Antimicrobials:

• 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:

Although data are limited, any CYP3A4 inhibitor could increase the plasma concentrations of amiodarone, disopyramide, or quinidine. Toxicity including cardiac arrhythmias could result. Assume that all CYP3A4 inhibitors interact until proven otherwise.

Class 3: Assess Risk & Take Action if Necessary

• Consider Alternative:
• Azole Antifungals: Fluconazole appears to be a less potent inhibitor of CYP3A4 than itraconazole or ketoconazole, but in larger doses it also inhibits CYP3A4. Terbinafine (Lamisil) does not appear to affect CYP3A4.
• Macrolide Antibiotics: Unlike erythromycin, clarithromycin and troleandomycin, other macrolides such as azithromycin (Zithromax) and dirithromycin^* do not appear to inhibit CYP3A4. (^* not available in US)
• Monitor: Monitor for altered antiarrhythmic response if the CYP3A4 inhibitor is initiated, discontinued, or changed in dosage. Monitor for ECG changes indicating antiarrhythmic toxicity, and measure antiarrhythmic plasma concentrations as needed.