aution if simvastatin and rolapitant are used concurrently, and monitor for simvastatin-related adverse effects. Simvastatin is a CYP2D6 and P-glycoprotein (P-gp) substrate and rolapitant is a CYP2D6 and P-gp inhibitor; the inhibitory effect of rolapitant on CYP2D6 lasts for at least 7 days, and may last longer after single dose administration. The Cmax and AUC of another CYP2D6 substrate, dextromethorphan, were increased by 120% and 160%, respectively, on day 1 with rolapitant, and by 180% and 230%, respectively, on day 8 after rolapitant administration. When rolapitant was administered with another P-gp substrate, digoxin, the day 1 Cmax and AUC were increased by 70% and 30%, respectively; the Cmax and AUC on day 8 were not studied.
Sapropterin: Caution is advised with the concomitant use of sapropterin and simvastatin as coadministration may result in increased systemic exposure of simvastatin. Simvastatin is a substrate for the drug transporter P-glycoprotein (P-gp); in vitro data show that sapropterin may inhibit P-gp. If these drugs are used together, closely monitor for increased side effects of simvastatin.
Saquinavir: 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.
Simeprevir: Coadministration of simvastatin with simeprevir, an inhibitor of OATP1B1 and intestinal CYP3A4, results in increased simvastatin plasma concentrations. If these drugs are given together, titrate the simvastatin dose carefully and use the lowest effective dose.
Sodium Bicarbonate: Antacids may decrease the peak plasma concentration (Cmax) of total ezetimibe by 30%. The effect of the antacids in this regard is not expected to have a significant effect on the ability of ezetimibe to lower cholesterol. However, to limit any potential interaction, it would be prudent to administer ezetimibe at least 1 hour before or 2 hours after administering antacids.
Sofosbuvir; Velpatasvir: Use caution when administering velpatasvir with simvastatin. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp). Additionally, velpatasvir is an inhibitor of the organic anion transporting polypeptides OATP1B1 and OATP1B3. Simvastation is an OATP substrate.
St. John's Wort, Hypericum perforatum: St. John's Wort appears to induce several isoenzymes of the hepatic cytochrome P450 enzyme system, including CYP3A4, CYP1A2, and potentially CYP2C9. Co-administration of St. John's wort could decrease the efficacy of some medications metabolized by these enzymes including simvastatin.
Streptogramins: Dalfopristin; quinupristin has been shown to inhibit CYP3A4 and may decrease the elimination of simvastatin, a CYP3A4 substrate.
Tacrolimus: The risk of developing myopathy during therapy with HMG-CoA reductase inhibitors may be increased when used with tacrolimus.
Telaprevir: The concurrent use of simvastatin and |
