OBJECT DRUGS

• Ranolazine (Ranexa)

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:

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.

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.
• 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.
• Circumvent/Minimize: Consider reducing the dose of ranolazine if enzyme inhibitors are coadministered. The ranolazine label states that when ranolazine is combined with moderate CYP3A4 inhibitors, the ranolazine dose should not exceed 500 mg twice daily.
• 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.