ain pathway was thought to be competitive P-gp inhibition. Caution is therefore warranted when combining atorvastatin, lovastatin, red yeast rice (structurally similar to lovastatin), or simvastatin with esomeprazole, lansoprazole, omeprazole, or pantoprazole. Substituting with dexlansoprazole or rabeprazole may represent a safer alternative. Treatment with pravastatin, fluvastatin, and rosuvastatin may also decrease the risk of a P-gp interaction.
Pazopanib: Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and simvastatin, a CYP3A4 substrate, may cause an increase in systemic concentrations of simvastatin. Use caution when administering these drugs concomitantly.
Peginterferon Alfa-2b: Monitor for adverse effects associated with increased exposure to simvastatin if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while simvastatin is partially metabolized by the CYP2D6 isoenzyme.
Perindopril; Amlodipine: Simvastatin and amlodipine should be coadministered with caution due to an increased risk of myopathy, including rhabdomyolysis. If amlodipine and simvastatin must be administered together, do not exceed 20 mg/day simvastatin in adults. For adult patients chronically receiving simvastatin 80 mg/day who need to be started on amlodipine, the manufacturer of simvastatin recommends switching to an alternative statin with less potential for interactions.
Posaconazole: The concurrent use of posaconazole and simvastatin is contraindicated due to the risk of myopathy, rhabdomyolysis, and acute renal failure. If therapy with posaconazole is unavoidable, simvastatin therapy must be suspended during the course of posaconazole treatment. There are no known adverse effects with short-term discontinuation of simvastatin.
Propranolol: After administration of single doses of simvastatin and propranolol, there was a significant decrease in mean Cmax, with no change in AUC, of simvastatin. The clinical significance of this interaction is unknown. Monitor for potential reduced cholesterol-lowering efficacy when propranolol is coadministered with niacin; simvastatin.
Protease inhibitors: 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.
Quinine: Simvastatin is a CYP3A4 substrate; therefore, quinine has the potential to inhibit the metabolism of simvastatin leading to an increased potential of rhabdomyolysis. Patients receiving concomitant simvastatin and quinine should be monitored closely for muscle pain or weakness. Lower starting doses of simvastatin should be considered while patients are receiving quinine.
Raltegravir: Raltegravir use has been associated with elevated creatinine kinase concentrations; myopathy and rhabdomyolysis have been reported. Use raltegravir cautiously with drugs that increase the risk of myopathy or rhabdomyolysis such as HMG-CoA reductase inhibitors (Statins).
Ranolazine: Simvastatin and ranolazine should be coadministe |
