Drug Interaction Report

CONTRAINDICATED: Rhabdomyolysis has been reported in patients receiving mibefradil and simvastatin. In vitro studies predict that mibefradil inhibits the metabolism of drugs that are substrates of the CYP450 microsomal pathway. HMG-CoA reductase inhibitors are metabolized to varying degrees by this pathway.

MANAGEMENT: The use of mibefradil with simvastatin and lovastatin is considered contraindicated, while the use of mibefradil with cerivastatin or atorvastatin is strongly discouraged by the manufacturers. Fluvastatin and pravastatin may be the preferred alternatives if an HMG-CoA reductase inhibitor must be used with mibefradil, since they are not significantly metabolized by the CYP450 pathway. Consideration should also be given to alternative antihypertensive therapy. However, if these agents must be used together, close observation for evidence of altered clinical effect is recommended. Additionally, the use of any HMG-CoA reductase inhibitor is not recommended in combination with mibefradil and either cyclosporine or tacrolimus, since additive inhibition of the metabolism of the HMG-CoA reductase inhibitor would be expected.

MONITOR: Concomitant use of statin medication with substantial quantities of alcohol may increase the risk of hepatic injury. Transient increases in serum transaminases have been reported with statin use and while these increases generally resolve or improve with continued therapy or a brief interruption in therapy, there have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins. Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury. Active liver disease or unexplained transaminase elevations are contraindications to statin use.

MANAGEMENT: Patients should be counseled to avoid substantial quantities of alcohol in combination with statin medications and clinicians should be aware of the increased risk for hepatotoxicity in these patients.