OBJECT DRUGS

• Ranolazine (Ranexa)

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:

Ranolazine is metabolized primarily by CYP3A4, and inhibitors of this isozyme increase the serum concentrations of ranolazine. The product information states that ranolazine is contraindicated with potent or moderately potent CYP3A4 inhibitors. Theoretically, such drugs could increase the risk of ranolazine-induced QTc prolongation and ventricular arrhythmias.

Class 2: Use Only if Benefit Felt to Outweight Risk

• Use Alternative:
• Azole Antifungals: Itraconazole and ketoconazole are potent inhibitors of CYP3A4; fluconazole appears weaker, but in larger doses it also inhibits CYP3A4.
• 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 may be considered.
• Circumvent/Minimize: Consider reducing the dose of 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.