Zocor Drug Interactions

Multiple mechanisms may contribute to potential interactions with HMG Co-A reductase inhibitors. Drugs or herbal products that inhibit certain enzymes (e.g. CYP3A4) and/or transporter (e.g. OATP1B) pathways may increase simvastatin and simvastatin acid plasma concentrations and may lead to an increased risk of myopathy/rhabdomyolysis.
Consult the prescribing information of all concomitantly used drugs to obtain further information about their potential interactions with simvastatin and/or the potential for enzyme or transporter alterations and possible adjustments to dose and regimens.
Contraindicated drugs: Concomitant use of the following drugs is contraindicated: Potent Inhibitors of CYP3A4: Simvastatin is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity; therefore it is not expected to affect the plasma concentrations of other drugs metabolized by CYP3A4. Potent inhibitors of CYP3A4 increase the risk of myopathy by reducing the elimination of simvastatin. Concomitant use of drugs labeled as having a potent inhibitory effect on CYP3A4 (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, drugs containing cobicistat) is contraindicated. See Contraindications; Myopathy/Rhabdomyolysis under Precautions.
Gemfibrozil, Cyclosporine or Danazol: See Myopathy/Rhabdomyolysis under Precautions.
Other drug interactions: Other Fibrates: The risk of myopathy is increased by gemfibrozil (see Contraindications) and other fibrates (except fenofibrate); these lipid-lowering drugs can cause myopathy when given alone. When simvastatin and fenofibrate are given concomitantly, there is no evidence that the risk of myopathy exceeds the sum of the individual risks of each agent. See Contraindications; Myopathy/Rhabdomyolysis under Precautions.
Fusidic Acid: The risk of myopathy/rhabdomyolysis may be increased by concomitant administration of fusidic acid (see Myopathy/Rhabdomyolysis under Precautions; Actions).
Amiodarone: The risk of myopathy/rhabdomyolysis is increased by concomitant administration of amiodarone with simvastatin (see Dosage & Administration; Myopathy/Rhabdomyolysis under Precautions).
Calcium channel blockers: The risk of myopathy/rhabdomyolysis is increased by concomitant administration of verapamil, diltiazem, or amlodipine (see Dosage & Administration; Myopathy/Rhabdomyolysis under Precautions).
Moderate Inhibitors of CYP3A4: Patients taking other medicines labeled as having a moderate inhibitory effect on CYP3A4 concomitantly with simvastatin, particularly higher simvastatin doses, may have an increased risk of myopathy (see Myopathy/Rhabdomyolysis under Precautions).
Inhibitors of Breast Cancer Resistant Protein (BCRP): Concomitant administration of medicinal products that are inhibitors of BCRP, including products containing elbasvir or grazoprevir, may lead to increased plasma concentrations of simvastatin and an increased risk of myopathy (see Dosage & Administration; Myopathy/Rhabdomyolysis under Precautions).
Niacin (nicotinic acid) (≥1 g/day): Cases of myopathy/rhabdomyolysis have been observed with simvastatin coadministered with lipid-modifying doses (≥1 g/day) of niacin (see Myopathy/Rhabdomyolysis under Precautions).
Colchicine: Cases of myopathy, including rhabdomyolysis, have been reported with simvastatin coadministered with colchicine. Caution should be exercised when prescribing simvastatin with colchicine.
Daptomycin: The risk of myopathy and/or rhabdomyolysis may be increased by coadministration of HMG-CoA reductase inhibitors and daptomycin (see Myopathy/Rhabdomyolysis under Precautions).
Other interactions: Grapefruit juice contains one or more components that inhibit CYP3A4 and can increase the plasma levels of drugs metabolized by CYP3A4.
Coumarin Derivatives: In two clinical studies, one in normal volunteers and the other in hypercholesterolemic patients, simvastatin 20-40 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. In patients taking coumarin anticoagulants, prothrombin time should be determined before starting simvastatin and frequently enough during early therapy to ensure that no significant alteration of prothrombin time occurs. Once a stable prothrombin time has been documented, prothrombin times can be monitored at the intervals usually recommended for patients on coumarin anticoagulants. If the dose of simvastatin is changed or discontinued, the same procedure should be repeated. Simvastatin therapy has not been associated with bleeding or with changes in prothrombin time in patients not taking anticoagulants.