Abstracts

Rationale: Drug interactions are common particularly related to polytherapy with the enzyme inducing AED (EIAEDs). Two of the most commonly prescribed AEDs, phenytion (PHT) and carbamazepine (CBZ), are strong enzyme inducers. Increasingly, patient taking the older AI-AEDs are being converted to newer AEDs such as topiramate. Enzyme induction has been studied extensively but little is known about loss of the induction affect (de-induction) of the EI-AED. Defining the time course of and effect of dose on de-induction will assist the clinician in managing the patient being converted to topiramate monotherapy.Methods: Patients were recruited taking PHT or CBZ that for clinical reasons were to be treated with topiramate and have the PHT or CBZ tapered and discontinued. Exclusions included clinically unstable medical or psychiatric disease and concurrent medications that may inhibit or induce metabolism of TPM. Serial blood samples were obtained on during the taper of PHT or CBZ and over the first 3 months of TPM monotherapy. Dosage reduction of PHT and CBZ were done every 2 weeks to ensure a new steady state plasma level was acheived and allowing time for the de-induction process to occur. Dosage of TPM was increased if seizure occurred during study thus TPM clearance values were calculated and used to describe outcome. Results: Twenty patient were studied who were taking either PHT (n=9) or CBZ (n=11). Patient demographics were: Ages - 27 to 62 yrs; race White-9, Black-5, Hispanic-4 and Asian-1; BMIs - 23 to 36. Before dosage reduction of the EI-AED, the average TPM clearance was 75 l/kg. This dropped to 61 l/kg the day the EI-AED was discontinued and declined further to 46 l/kg at the lowest. At 9 days after the EI-AED was discontinued most of the induction effect was lost.Conclusions: Half of the de-induction effect occurs after the EI-AED is discontinued and the majority of the change is evident within the first two weeks. Approximately half of de-induction occurs during the reduction of the EI-AED. De-induction is complete by six weeks after EI-AED is stopped. The clearance is reduced on an average by 60% which would result in more than doubling of TPM levels after PHT or CBZ is discontinued.