POTENTIAL PHARMACOKINETIC INTERACTION BETWEEN FELBAMATE AND PHENOBARBITAL

OBJECTIVE: To report a case of a potential pharmacokinetic interaction between felbamate and phenobarbital in a patient with epilepsy. CASE SUMMARY: A patient with a history of a mixed seizure disorder and stat ic encephalopathy who was receiving sodium valproate 750 mg/d and phen obarbital 230 mg/d was initiated on felbamate (as part of a compassion ate use program). Upon instituting felbamate, valproate dosage was red uced to 500 mg/d and phenobarbital to 200 mg/d. Felbamate dosage was t itrated to approximately 50 mg/kg/d over three weeks, In this patient, plasma phenobarbital concentrations increased from 48 mug/mL to 68 mu g/mL, at which point the patient was hospitalized because of clinicall y significant neurotoxicity. Phenobarbital dosage was subsequently red uced to 150 mg/d; this resulted in phenobarbital trough concentrations of 60 mug/mL. CONCLUSIONS: Felbamate has been shown previously to int eract with multiple other anticonvulsant medications, including valpro ate, phenytoin, and carbamazepine. Felbamate appears to decrease the c learance of valproate, phenytoin, and carbamazepine epoxide to a signi ficant extent, an effect that may be the result of inhibition of the m etabolism of these compounds. Carbamazepine plasma concentrations have been demonstrated to decrease following administration of felbamate, suggesting metabolic induction. It is reasonable to suggest that based on these findings and the observations in our patient, felbamate come dication may result in clinically significant increases in plasma phen obarbital concentrations. It would seem prudent, therefore, when initi ating or adjusting felbamate therapy in patients receiving this drug c ombination, to monitor phenobarbital plasma concentrations.