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.