Lipid lowering inefficacy of high-dose statin therapy due to concurrent use of phenytoin

HMG-CoA reductase inhibitors ("statins") are the most commonly prescribed lipid lowering agents. Most of the statins are metabolized by the CYP450 cytochrome system. A number of medications either induce or inhibit this system which leads to changes in the bioavailability of the statins and the potential for either an increase in adverse effects or reduction in efficacy. Phenytoin induces the CYP3A4 isoform of the CYP450 system and can reduce the bioavailability, and thus the efficacy of the statins metabolized by this enzyme, including atorvastatin and lovastatin. A case of a patient on multiple lipid-lowering medications, including high-dose atorvastatin whose LDL cholesterol improved significantly after discontinuation of phenytoin is presented, and a review of the literature for similar cases is discussed.