red with caution due to an increased risk of myopathy, including rhabdomyolysis. If ranolazine and simvastatin must be administered together, do not exceed 20 mg/day simvastatin in adults. For patients chronically receiving simvastatin 80 mg/day who need to be started on ranolazine, the manufacturer of simvastatin recommends switching to an alternative statin with less potential for interactions. The plasma concentrations of simvastatin, a CYP3A4 substrate, and its active metabolite are each increased about 2-fold in healthy subjects receiving simvastatin (80 mg once daily) and ranolazine (1000 mg twice daily). In contrast, simvastatin (20 mg once daily) does not increase the exposure to ranolazine in healthy adult volunteers.
Red Yeast Rice: Since compounds in red yeast rice claim to have HMG-CoA reductase inhibitor activity, red yeast rice should not be used in combination with HMG-CoA reductase inhibitors. The administration of more than one HMG-CoA reductase inhibitor at one time would be duplicative therapy and perhaps increase the risk of drug-related toxicity including myopathy and rhabdomyolysis.
Repaglinide: Coadministration of may lead to an increase in repaglinide. This interaction could result in an increased risk of adverse effects associated with repaglinide, specifically hypoglycemia.
Rifabutin: Rifabutin may induce the CYP3A4 metabolism of simvastatin. Monitor for potential reduced cholesterol-lowering and hypotensive efficacy when these drugs are coadministered.
Rifampin: Rifampin has been reported to significantly increase the plasma clearance and decrease the serum concentrations of simvastatin. Monitor for potential reduced cholesterol-lowering and hypotensive efficacy when these drugs are coadministered.
Rifapentine: Rifapentine may induce the CYP3A4 metabolism of simvastatin. Monitor for potential reduced cholesterol-lowering and hypotensive efficacy when these drugs are coadministered.
Rifaximin: Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and simvastatin, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Ritonavir: 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.
Rivaroxaban: Coadministration of rivaroxaban and simvastatin may result in increases in rivaroxaban exposure and may increase bleeding risk. Simvastatin is an inhibitor of P-gp, and rivaroxaban is a substrate of P-gp. If these drugs are administered concurrently, monitor the patient for signs and symptoms of bleeding.
Rolapitant: Use c |
