OBJECT DRUGS

• Ivabradine (Corlanor)

PRECIPITANT DRUGS

Enzyme Inhibitors:

• Amiodarone (Cordarone, etc.)
• Amprenavir (Agenerase)
• Aprepitant (Emend)
• Atazanavir (Reyataz)
• Boceprevir (Victrelis)
• Ceritinib (Zykadia)
• Cobicistat (Stribild)
• Conivaptan (Vaprisol)
• Cyclosporine (Neoral, etc.)
• Darunavir (Prezista)
• Delavirdine (Rescriptor)
• Dronedarone (Multaq)
• Grapefruit
• Imatinib (Gleevec)
• Indinavir (Crixivan)
• Lapatinib (Tykerb)
• Lomitapide (Juxtapid)
• Mifepristone (Korlym)
• Nelfinavir (Viracept)
• Ritonavir (Norvir)
• Saquinavir (Invirase)
• Telaprevir (Incivek)

Comment:

Ivabradine is a CYP3A4 substrate, and 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: If possible, avoid using ivabradine and CYP3A4 inhibitors concurrently.
• Grapefruit: Orange juice does not appear to inhibit CYP3A4.
• Monitor: If the combination is used, monitor for ivabradine toxicity, including bradycardia.