OBJECT DRUGS

• Ivabradine (Corlanor)

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:

Ivabradine is a CYP3A4 substrate, and antimicrobials that are CYP3A4 inhibitors may increase the risk of ivabradine toxicity. The strong CYP3A4 inhibitor, ketoconazole, produced about a 7-fold increase in ivabradine AUC, and the product information for ivabradine lists strong CYP3A4 inhibitors as contraindicated with ivabradine. There is considerable variability in the magnitude of such interactions from patient to patient, however, so it would be prudent to avoid both moderate and strong CYP3A4 inhibitors in patients on ivabradine.

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 ivabradine.
• 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: If the combination is used, monitor for ivabradine toxicity, including bradycardia.