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.
Dasatinib: Dasatinib is a time-dependent, weak inhibitor of CYP3A4. Therefore, caution is warranted when drugs that are metabolized by this enzyme like simvastatin are administered concurrently with dasatinib as increased adverse reactions may occur.
Deferasirox: The concomitant administratin of midazolam, a CYP3A4 substrate, and deferasirox resulted in a decrease in the peak serum concentration of midazolam by 23% and midazolam exposure by 17% in healthy volunteers. This effect may be even more pronounced in patients. Although not specifically studied, reduced serum concentrations may also occur in patients taking other CYP3A4 substrates such as simvastatin. If these drugs are used together, monitor patients for a decrease in the effects of simvastatin.
Delavirdine: The risk of myopathy, including rhabdomyolysis, may be increased when delavirdine is given in combination with HMG-CoA reductase inhibitors. Concomitant use of delavirdine and the CYP3A4 substrate simvastatin is not recommended. If treatment with an HMG-CoA reductase inhibitor is necessary, pravastatin should also be considered, since it is not significantly metabolized by CYP3A4 or CYP2C9 isoenzymes.
Digoxin: Simvastatin causes a slight elevation of serum digoxin levels. Simvastatin should be used cautiously in patients receiving digoxin.
Diltiazem: Simvastatin and diltiazem, a CYP3A4 inhibitor, should be coadministered with caution due to an increased risk of myopathy, including rhabdomyolysis. Consider use of a non-CYP3A4-metabolized statin (e.g., pitavastatin, pravastatin, rosuvastatin) in combination with diltiazem. If simvastatin and diltiazem must be administered together, do not exceed 10 mg/day simvastatin or 240 mg/day of diltiazem in adults. For patients chronically receiving simvastatin 80 mg/day who need to be started on diltiazem, the manufacturer of simvastatin recommends switching to an alternative statin with less potential for interactions. In a study of 10 healthy subjects, a single 20 mg oral dose of simvastatin administered after 2 weeks of diltiazem 240 mg/day PO significantly increased the mean Cmax of simvastatin and simvastatin acid by about 3.6-fold and 3.7-fold, respectively and the AUC of simvastatin by 5-fold. The interaction occurred to a greater extent in individuals who had the greatest serum concentrations of diltiazem.
Doxorubicin: Simvastatin is a P-glycoprotein (P-gp) inhibitor and doxorubicin is a major substrate of P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of P-gp, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of simvastatin and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
Dronedarone: Do not exceed 10 mg/day PO simvastatin if concurrent administration with dronedarone is necessary. |
