Interactions between ranexa(ranolazine) and Cardizem la (diltiazem)
diltiazem and ranolazine (Major Drug-Drug)
CONTRAINDICATED: Coadministration with potent and moderately potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of ranolazine, which is primarily metabolized by the isoenzyme. Because ranolazine prolongs QT interval in a dose-dependent manner, high plasma levels of ranolazine may increase the risk of ventricular arrhythmias such as ventricular tachycardia, ventricular fibrillation, and torsade de pointes. In pharmacokinetic studies, plasma levels of ranolazine (1000 mg twice a day) were increased 3.2-fold by the potent CYP450 3A4 inhibitor, ketoconazole (200 mg twice a day), and 1.8- to 2.3-fold by the moderately potent inhibitor diltiazem (180 to 360 mg/day). Plasma levels of ranolazine (750 mg twice a day) were increased about 2-fold by the CYP450 3A4 and P-glycoprotein inhibitor, verapamil (120 mg three times a day).
MANAGEMENT: Ranolazine should not be used in combination with potent or moderately potent CYP450 3A4 inhibitors, including but not limited to diltiazem, verapamil, nefazodone, delavirdine, azole antifungal agents, protease inhibitors, and ketolide and certain macrolide antibiotics.
