OBJECT DRUGS

• Ranolazine (Ranexa)

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)
• Diltiazem (Cardizem, etc.)
• Dronedarone (Multaq)
• Grapefruit
• Imatinib (Gleevec)
• Indinavir (Crixivan)
• Lapatinib (Tykerb)
• Lomitapide (Juxtapid)
• Mifepristone (Korlym)
• Nelfinavir (Viracept)
• Ritonavir (Norvir)
• Saquinavir (Invirase)
• Telaprevir (Incivek)
• Verapamil (Isoptin, etc.)

Comment:

Ranolazine is metabolized primarily by CYP3A4, and inhibitors of this isozyme increase the serum concentrations of ranolazine. Theoretically, such drugs could increase the risk of ranolazine-induced QTc prolongation and ventricular arrhythmias. The product information states that ranolazine is contraindicated with potent CYP3A4 inhibitors. Because amiodarone inhibits CYP3A4 and also intrinsically prolongs the QTc interval, it would be wise to avoid combining it with ranolazine (Class 1) .

Class 2: Use Only if Benefit Felt to Outweigh Risk

• Use Alternative: Use an alternative to the enzyme inhibitor if possible.
• Calcium Channel Blockers: Calcium channel blockers other than diltiazem and verapamil are unlikely to inhibit CYP3A4.
• Grapefruit: Orange juice does not appear to inhibit CYP3A4.
• Circumvent/Minimize: Consider reducing the dose of the ranolazine if enzyme inhibitors are coadministered.
• Monitor: If the combination is used, the primary concern is QTc prolongation. Monitor the ECG and advise the patient to report any episodes of dizziness or syncope.