lycemia.
Mifepristone, RU-486: Mifepristone, RU-486 inhibits CYP3A4 in vitro. Coadministration of mifepristone may lead to an increase in serum concentrations of drugs that are CYP3A4 substrates and that have a narrow therapeutic index. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration. When used in the treatment of Cushing's syndrome, coadministration of mifepristone with simvastatin is contraindicated based on studies demonstrating significant drug exposure increases which may lead to an increased risk of myopathy and rhabdomyolysis.
Mirabegron: Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized partially by CYP2D6, such as simvastatin, may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Mitotane: Use caution if mitotane and simvastatin are used concomitantly, and monitor for decreased efficacy of simvastatin and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and simvastatin is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of simvastatin.
Nefazodone: Nefazodone is contraindicated during simvastatin therapy due to the increased risk of myopathy. Nefazodone may reduce the metabolism of simvastatin via inhibition of the hepatic CYP3A4 isoenzyme. Both rhabdomyolysis and myositis have been reported in the literature secondary to concurrent administration of nefazodone with simvastatin.
Nelfinavir: 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.
Netupitant; Palonosetron: Netupitant is a moderate inhibitor of CYP3A4 and should be used with caution in patients receiving concomitant medications that are primarily metabolized through CYP3A4, such as simvastatin. The plasma concentrations of simvastatin can increase when co-administered with netupitant; the inhibitory effect on CYP3A4 can last for multiple days.
Nevirapine: Nevirapine, which is a CYP3A4 inducer, may decrease the efficacy of HMG-Co-A reductase inhibitors which are CYP3A4 substrates including simvastatin. Monitor for potential reduced cholesterol-lowering efficacy when these drugs are co-administered with HMG-CoA reductase inhibitors which are metabolized by CYP3A4.
Niacin, Niacinamide: 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 drug |
