mibe does not affect the pharmacokinetics of fenofibrate or the bioavailability of gemfibrozil.
Flibanserin: In a cross-over study in 12 healthy men and women, the effect of flibanserin 50 mg twice daily for 4 days on the pharmacokinetics of simvastatin 40 mg once daily was eva luated. Flibanserin increased the AUC of simvastatin, a substrate of CYP3A4, by 1.3-fold and the Cmax by 1.2-fold. The AUC and Cmax of simvastatin acid were increased by 1.5-fold and 1.4-fold, respectively.
Fluconazole: The risk of developing myopathy, rhabdomyolysis, and acute renal failure is increased if simvastatin is administered concomitantly with CYP3A4 inhibitors including systemic fluconazole. There are no known adverse effects with short-term discontinuation of simvastatin; discontinuation of simvastatin may be advisable when concurrent short-term therapy with systemic fluconazole is needed.
Fluvoxamine: Coadministration of fluvoxamine (CYP3A4 inhibitor) and simvastatin (CYP3A4 substrate) would be expected to result in an increase in simvastatin serum concentrations. Elevation of simvastatin serum concentrations can increase the risk of myopathy and rhabdomyolysis, particularly with higher doses of simvastatin. Monitor patients receiving concomitant simvastatin and fluvoxamine closely for muscle pain or weakness.
Fosamprenavir: The coadministration of anti-retroviral protease inhibitors with simvastatin is contraindicated. Taking these drugs together may significantly increase the serum concentration of simvastatin; thereby increasing the risk of myopathy and rhabdomyolysis. One report has demonstrated that ritonavir plus saquinavir therapy markedly increases the AUC for simvastatin by 3059%. Simvastatin is a substrate for CYP3A4 and the drug transporter organic anion transporting polypeptide (OATP1B1); protease inhibitors are CYP3A4 and OATP inhibitors.
Gemfibrozil: The use of simvastatin with gemfibrozil is contraindicated due to an increased risk for myopathy and rhabdomyolysis. Gemfibrozil can cause myopathy when used alone, and the risk of myopathy and rhabdomyolysis is increased by concomitant use with simvastatin. In addition, the AUC and Cmax of simvastatin are increased with concomitant gemfibrozil use. This may be due to inhibition of OATP1B1 by gemfibrozil; simvastatin is a substrate of OATP1B1. The safety and effectiveness of ezetimibe when coadministered with gemfibrozil have not been established. Fibrates may increase cholesterol excretion into the bile, leading to cholelithiasis. Coadministration of ezetimibe with gemfibrozil is not recommended. In a preclinical study in dogs, ezetimibe increased cholesterol in the gallbladder bile. The incidence rates for cholecystectomy have been reported as 0.6% for fenofibrate monotherapy and 1.7% for combination therapy (ezetimibe plus fenofibrate), respectively. According to the manufacturer, the number of patients exposed to combination therapy versus fenofibrate or ezetimibe monotherapy has been inadequate to assess gallbladder disease risk. If cholelithiasis is suspected in a patient receiving ezetimibe and fenofibrate, gallbladder studies are indicated and alternative lipid-lowering therapy should be considered. In a pharmacokinetic study, concomitant fenofibrate or gemfibrozil administration increased total ezetimibe concentrations by approximately 1.5- or 1.7-fold, respectively. However, ezetimibe does not affect the pharmacokinetics of fenofibrat |
