e or the bioavailability of gemfibrozil.
Grapefruit juice: Large quantities of grapefruit juice are contraindicated during simvastatin therapy due to the increased risk of myopathy. Grapefruit juice contains compounds that inhibits the CYP3A4 isozyme in the gut wall. Coadministration with grapefruit juice increases the peak serum concentrations and the AUC of lovastatin and may have a similar effect on the serum concentrations of simvastatin. Grapefruit juice should be avoided or minimized in patients taking simvastatin to avoid the potential for myopathy and rhabdomyolysis.
Hydantoins: Hydantoin anticonvulsants induce hepatic microsomal enzymes and may increase the metabolism of other drugs, such as simvastatin, leading to reduced efficacy of simvastatin.
Hydrochlorothiazide, HCTZ; 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.
Idelalisib: Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with simvastatin, a CYP3A substrate, as simvastatin toxicities, such as the risk for myopathy, may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Consider an alternative to simvastatin. A single dose of 10 mg of rosuvastatin was administered alone and after idelalisib 150 mg for 12 doses in healthy subjects and no changes in exposure to rosuvastatin were observed.
Imatinib, STI-571: Imatinib, STI-571 inhibits the metabolism of simvastatin via CYP3A4. Concurrent use of simvastatin and imatinib resulted in 2- and 3.5-fold increases in simvastatin Cmax and AUC values, respectively. Increases in serum concentrations of simvastatin may lead to myopathy and rhabdomyolysis.
Indinavir: 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.
Isavuconazonium: Concomitant use of isavuconazonium with simvastatin may result in increased serum concentrations of simvastatin. Simvastatin is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together.
Isoniazid, INH; Pyrazinamide, PZA; 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.
Isoniazid, INH; 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 dr |
