s known to increase the risk of developing rhabdomyolysis or acute renal failure. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage.
Niacin; Simvastatin: The risk of myopathy increases when HMG-Co-A reductase inhibitors are administered concurrently with antilipemic doses of niacin (i.e., 1 g per day or more). Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy. When possible, avoid concurrent use of HMG-reductase inhibitors with drugs known to increase the risk of developing rhabdomyolysis or acute renal failure. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage.
Nicardipine: Nicardipine is an inhibitor of CYP3A4 isoenzymes. Co-administration with nicardipine may lead to an increase in serum levels of drugs that are CYP3A4 substrates including simvastatin.
Nintedanib: Simvastatin is a moderate inhibitor of P-glycoprotein (P-gp) and nintedanib is a P-gp substrate. Coadministration may increase the concentration and clinical effect of nintedanib. If concomitant use of simvastatin and nintedanib is necessary, closely monitor for increased nintedanib side effects including gastrointestinal toxicity, elevated liver enzymes, and hypertension. A dose reduction, interruption of therapy, or discontinuation of therapy may be necessary.
Obeticholic Acid: Obeticholic acid may increase the exposure to simvastatin. Simvastatin is a substrate of OATP1B1 and OATP1B3 and obeticholic acid inhibits OAT1B1 and OATP1B3 in vitro. Caution and close monitoring is advised if these drugs are used together.
Olaparib: Use caution if coadministration of olaparib with simvastatin is necessary, due to an increased risk of simvastatin- and olaparib-related adverse reactions. Simvastatin is metabolized by CYP3A4 and 2D6, but is also an OATP1B1 and P-glycoprotein (P-gp) substrate, as well as a P-gp inhibitor. Olaparib is an in vitro OATP1B1 and P-gp inhibitor, as well as an in vitro P-gp substrate; the clinical relevance of these findings is unknown.
Ombitasvir; Paritaprevir; Ritonavir: Concomitant use of dasabuvir; ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir with simvastatin is contraindicated due to the potential for severe adverse reactions, including myopathy and rhabdomyolysis. Coadministration may result in elevated simvastatin systemic concentrations. Simvastatin is a substrate of the hepatic isoenzyme CYP3A4 and OATP1B1; ritonavir is a potent inhibitor of CYP3A4 and paritaprevir inhibits OATP1B1. In addition, simvastatin may inhibit P-glycoprotein (P-gp), a drug efflux transporter for which dasabuvir, ombitasvir, paritaprevir and ritonavir are substrates. The coadministration of anti-retroviral protease inhibitors with simvastatin is contraindicated. Taking these dr |
