telaprevir is contraindicated due to the potential for serious/life-threatening reactions. Telaprevir is an inhibitor of CYP3A4, which is responsible simvastatin metabolism. Coadministration may result in large increases in simvastatin serum concentrations, which could cause adverse events such as myopathy and rhabdomyolysis.
Telbivudine: The risk of myopathy may be increased if an HMG-CoA reductase inhibitor is coadministered with telbivudine. Monitor patients for any signs or symptoms of unexplained muscle pain, tenderness, or weakness, particularly during periods of upward dosage titration.
Telithromycin: Telithromycin is contraindicated during simvastatin therapy. Telithromycin potently inhibits the metabolism of simvastatin via the CYP3A4 isoenzyme and increases the risk of myopathy and rhabdomyolysis. According to the manufacturer, therapy with simvastatin must be suspended during the course of telithromycin treatment. There are no known adverse effects with short-term discontinuation of simvastatin. Pharmacokinetic studies have reported increased simvastatin concentrations due to CYP3A4 inhibition by telithromycin. When the two drugs were co-administered, there was a 5.3-fold increase in simvastatin Cmax, an 8.9-fold increase in the AUC, a 15-fold increase in the active metabolite Cmax, and a 12-fold increase in the active metabolite AUC. In another study, when simvastatin and telithromycin were administered 12 hours apart, there was a 3.4-fold increase in simvastatin Cmax, a 4-fold increase in AUC, a 3.2-fold increase in the active metabolite Cmax, and a 4.3-fold increase in the active metabolite AUC. Increased serum concentrations of HMG-CoA reductase inhibitors are associated with myopathy. Additionally, simvastatin is a substrate for organic anion transport protein (OATP) and telithromycin may act as an inhibitor for the hepatic organic anion transport protein (OATP) uptake transporters OATP1B1 and OATP1B3.
Temsirolimus: Use caution if coadministration of temsirolimus with simvastatin is necessary, and monitor for an increase in temsirolimus- and simvastatin-related adverse reactions. Temsirolimus is a P-glycoprotein (P-gp) substrate / inhibitor in vitro, while simvastatin is also a P-gp substrate / inhibitor. Pharmacokinetic data are not available for concomitant use of temsirolimus with P-gp inhibitors or substrates, but exposure to both simvastatin and temsirolimus (and active metabolite, sirolimus) is likely to increase.
Tenofovir Alafenamide: Caution is advised when administering tenofovir alafenamide concurrently with simvastatin as coadministration may result in elevated tenofovir alafenamide plasma concentrations. Inhibitors of the drug transporter P-glycoprotein (P-gp), such as simvastatin, may increase absorption of tenofovir alafenamide, a P-gp substrate. If these medications are administered together, monitor for tenofovir-associated adverse reactions. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Tenofovir, PMPA: Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as simvastatin. Coadministration may result in increased absorption of tenofovir. Monitor for t |
