Elevation ofplasma phenytoin byviloxazine in epileptic patients: aclinically significant drug interaction

Theeffect ofviloxazine (150-300 mg daily for21days) on plasmaphenytoin levels at steady statewas examinedin10epileptic patients stabilised on a fixedphenytoin dosage. Afterstarting vioxazine treatment,plasmaphenytoin concentrations increased by37% on average (range794%)froma mean valueof18-8pglmlat baseline to a mean valueof257pg/ml duringthelastweekofcombinedtherapy. Infourpatients theriseinplasmaphenytoin was associated withthedevelopment ofsignsofphenytoin toxicity. Discontinuation ofviloxazine resulted inreturn ofplasmaphenytointowardsbaseline valuesanddisappearance oftheclinical symptoms.The mechanismofinteractionprobablyinvolvesinhibition of phenytoinmetabolismby viloxazine. Carefulmonitoring ofplasmaphenytoin levels isrecommendedinpatients treated withphenytoin whoneedtobestarted on vioxazine therapy.