Drug interactions between Carbatrol and simvastatin

GENERALLY AVOID: Coadministration with carbamazepine may significantly decrease the plasma concentrations of simvastatin and its pharmacologically active acid metabolite. The proposed mechanism is carbamazepine induction of the intestinal and hepatic CYP450 3A4 metabolism of simvastatin and simvastatin acid. In 12 healthy volunteers, pretreatment with carbamazepine for 14 days (200 mg once daily for 2 days, then 300 mg twice daily) decreased the mean total area under the serum concentration-time curve (AUC) of simvastatin and simvastatin acid by 75% and 82%, respectively, compared to administration of simvastatin (80 mg single oral dose) alone. In the presence of carbamazepine, the mean peak concentrations (Cmax) of both simvastatin and simvastatin acid were reduced by 68%, and the half-life of simvastatin acid was shortened from 5.9 to 3.7 hours. The interaction was apparent in every subject of the study.

MANAGEMENT: Given the magnitude of the interaction, the pharmacologic effect of simvastatin may be significantly reduced during concomitant administration with carbamazepine. Therefore, concurrent use should preferably be avoided. If the combination is prescribed, the dosage of simvastatin may need to be increased. Alternatively, use of another HMG-CoA reductase inhibitor (i.e., statin) that is not significantly metabolized by CYP450 3A4 may be considered. As carbamazepine is known to induce other CYP450 isoenzymes besides 3A4, the statins least likely to interact may be pravastatin, which is metabolized by non-CYP routes, and rosuvastatin, which is only about 10% metabolized.