Efficacy of statin therapy: possible effect of phenytoin

Statins are currently the most widely prescribed lipid-lowering drugs. Individual statins are known to be metabolised by the CYP3A4 isoform of the cytochrome P450 system. The effect of CYP3A4 inducers such as phenytoin on the metabolism and efficacy of these agents is unknown. We report a patient with familial hypercholesterolaemia and epilepsy in whom the introduction and subsequent discontinuation of phenytoin were associated with marked changes in the lipid response to treatment with simvastatin and atorvastatin. The serum activity of gamma-glutamyl transpeptidase may have acted as a marker of microsomal induction by phenytoin, since it rose markedly when phenytoin was introduced and returned to normal after it was discontinued.