Verapamil: Verapamil has been shown to significantly increase the risk of myopathy due to simvastatin; the risk for myopathy is related to the dose of simvastatin. If verapamil and simvastatin must be administered together, do not exceed 10 mg/day simvastatin in adults. For patients chronically receiving simvastatin 80 mg/day who need to be started on verapamil, the manufacturer of simvastatin recommends switching to an alternative statin with less potential for interactions. In an analysis of clinical trials treated with simvastatin 20-80 mg/day, the incidence of myopathy was higher in patients receiving verapamil and simvastatin (0.63%; 4 of 635 patients) than in patients taking simvastatin without a calcium channel blocker (0.061%; 13 patients of 21,224 patients). Verapamil increases simvastatin serum concentrations (increased Cmax and AUC). The interaction is presumed due to increased simvastatin bioavailability via inhibition of CYP3A4 metabolism and reduction of first-pass metabolism.
Vincristine Liposomal: Simvastatin inhibits P-glycoprotein (P-gp), and vincristine is a P-gp substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Vincristine: Simvastatin inhibits P-glycoprotein (P-gp), and vincristine is a P-gp substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Vinorelbine: Caution is warranted when simvastatin is administered with vinorelbine as there is a potential for elevated vinorelbine concentrations; this may also apply to combination drugs that contain simvastatin, such as ezetimibe; simvastatin, niacin; simvastatin, and simvastatin; sitagliptin. Monitor patients for an earlier onset and/or an increased severity of adverse effects including neurotoxicity and myelosuppression. Vinorelbine is a substrate of P-glycoprotein (P-gp) and simvastatin is an inhibitor of P-gp.
Voriconazole: Concurrent use of simvastatin and voriconazole is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is increased if simvastatin is administered concomitantly with potent CYP3A4 inhibitors such as voriconazole. If therapy with voriconazole is unavoidable, simvastatin therapy must be suspended during voriconazole treatment. There are no known adverse effects with short-term discontinuation of simvastatin.
Warfarin: Coadministration with ezetimibe has not demonstrated significant effects on the bioavailability or the anticoagulant effects of warfarin when studied in 12 healthy adult males. However, according to the manufacturer, increases in PT/INR have been reported and accordingly recommends that if ezetimibe is added to warfarin, the INR should be monitored. Per prescribing information for warfarin sodium (Coumadin), all HMG-CoA reductase inhibitors (statins) have been associated with potentiation of warfarin's clinical effect. However, it appears that pravastatin and atorvastatin may be less likely to significantly interact with warfarin based on drug interaction studies. In addition, atorvastatin has been reported to slightly and transiently decrease the anticoagulant activity of warfarin; these effects were not considered clinically significant. In general, it is prudent to monitor INR at baseline, at initiation of these HMG Co-A reductase inhibitors, and after subsequent |
