In clinical trials of Zortress in kidney transplant recipients, concurrent use of simvastatin was strongly discouraged due to reported interactions between cyclosporine and simvastatin. Flibanserin: (Moderate) In a cross-over study in 12 healthy men and women, the effect of flibanserin 50 mg twice daily for 4 days on the pharmacokinetics of simvastatin 40 mg once daily was evaluated. All patients starting therapy with Simvastatin, or whose dose of Simvastatin is being increased, should be advised of the risk of myopathy, including rhabdomyolysis and told to report promptly any unexplained muscle pain, tenderness or weakness particularly if accompanied by malaise or fever or if muscle signs and symptoms persist after discontinuing Simvastatin. Coadministration of ivacaftor with simvastatin may increase simvastatin exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined. In two clinical studies, one in normal volunteers and the other in hypercholesterolemic patients, Simvastatin 20 to 40 mg/day modestly potentiated the effect of coumarin anticoagulants: the prothrombin time, reported as International Normalized Ratio (INR), increased from a baseline of 1.7 to 1.8 and from 2.6 to 3.4 in the volunteer and patient studies, respectively. Simvastatin is a medication included in the class of drugs called statins. Therefore, the 80 mg dose is restricted to patients who have taken 80 mg/day chronically (e.g. Being lipophilic, simvastatin is taken up by cells other than hepatocytes, and unlike pravastatin, simvastatin penetrates the CNS. Letermovir: (Major) Use of simvastatin with letermovir is not recommended due to increased simvastatin exposure. Coded "PD 156" on one side and "20" … Nefazodone may reduce the metabolism of simvastatin via inhibition of the hepatic CYP3A4 isoenzyme. There are no known adverse effects with short-term discontinuation of simvastatin; discontinuation of simvastatin may be advisable when concurrent short-term therapy with systemic fluconazole is needed. The AUC and Cmax of simvastatin acid were increased by 1.5-fold and 1.4-fold, respectively. Combination of these drugs with Simvastatin is contraindicated. Simvastatin is a sensitive CYP3A4 substrate and fedratinib is a moderate CYP3A inhibitor. Therefore, concomitant use of these drugs is contraindicated. Assess liver enzymes prior to initiation of simvastatin therapy and repeat as clinically indicated. The risk of myopathy is increased by elevated plasma levels of Simvastatin and Simvastatin acid. Simvastatin may need to be temporarily withheld in patients experiencing these conditions acutely. At these doses the only signs seen in dogs were emesis and mucoid stools. Riluzole: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and simvastatin. Conivaptan 30 mg/day IV results in a 3-fold increase in the AUC of simvastatin. Dabigatran: (Moderate) Consider a statin other than lovastatin or simvastatin if HMG-CoA reductase inhibition is necessary for a patient receiving dabigatran. In 89% of these cases, drug treatment was initiated prior to pregnancy and was discontinued during the first trimester when pregnancy was identified. With other statins, clinically evident bleeding and/or increased prothrombin time has been reported in a few patients taking coumarin anticoagulants concomitantly. La simvastatine réduit les taux de mauvais cholestérol et de triglycérides dans le sang, tout en augmentant la production de bon cholestérol. Common side effects include constipation, headaches, and nausea. A decision should be made whether to discontinue nursing or discontinue drug, taking into account the importance of the drug to the mother [see Contraindications (4)]. Rifapentine: (Minor) Rifapentine may induce the CYP3A4 metabolism of simvastatin. Cimetidine: (Major) Because HMG-CoA reductase inhibitors may theoretically blunt adrenal and/or gonadal steroid production by interfering with cholesterol synthesis, the manufacturer recommends caution with concomitant administration of drugs that may decrease the concentrations or activity of endogenous hormones, such as cimetidine. Use of these drugs together may result in elevated Statin serum concentrations, potentially resulting in adverse effects such as myopathy and rhabdomyolysis. In a clinical trial in which 12,064 patients with a history of myocardial infarction were treated with Simvastatin (mean follow-up 6.7 years), the incidence of myopathy (defined as unexplained muscle weakness or pain with a serum creatine kinase [CK] >10 times upper limit of normal [ULN]) in patients on 80 mg/day was approximately 0.9% compared with 0.02% for patients on 20 mg/day. Carefully weigh the benefits of combined use of bempedoic acid and simvastatin against the potential risks. Fenofibrate: (Major) Fenofibrate and simvastatin should administered concomitantly only with caution. Treatment with immunosuppressive agents may be required. There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including Simvastatin. Verapamil increases the simvastatin exposure by approximately 2-fold. Taking these drugs together may significantly increase the serum concentration of simvastatin; thereby increasing the risk of myopathy and rhabdomyolysis. Interference with the activity of this enzyme reduces the quantity of mevalonic acid, a precursor of cholesterol. Concomitant use may increase simvastatin exposure. Simvastatin occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase (CK) above ten times the upper limit of normal (ULN). Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
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