Tacrolimus—Phenytoin Interaction

TO THE EDITOR: We describe a possible interaction between tacrolimus and phenytoin, and suggest a possible mechanism and other factors to explain this interaction. Case Report. A 46-year-oldwhite man with a historyof renal insufficiency, statuspostkidneytransplant, hypertension, generalized seizuredisorder, anddiabetespresented to thehospital afteran episodeof syncope in his physician's office on thedayof admission. The patientwas admitted to the telemetry unit for monitoring. His heightand weightwere 193cm and 127kg, respectively. Hisphenytoin concentrationwas 36.2 pg/ml, (phenytoindosing data are in Table 1). An electrocardiogram showedno changesfroma previous study. His telemetry monitoring was normal and showed no arrhythmiasor ectopy. A prehospitalization medication regimenof azathioprine, bumetanide, digoxin,diltiazem, heparin, insulin,prednisone. and tacrolimus wascontinued. Phenytoin waswithheld. He had no seizure activity and his creatinine remained stable at around 4.9 mgldL throughout hospitalization. He required no dialysisand his urineoutputremained normal. On hospitalday 9 the phenytoinconcentration was 22.2 f1g1mL and the patientwas still free of syncopeor arrhythmias. Phenytoin was restartedand the patientwasdischarged home. The patienthada history of generalized seizures beginning at approximately 18 yearsof age.The seizures had beencontrolled withphenytoin. Priorto admission the patienthad been stabilized on a regimen of oral phenytoin 600 mgld alternating with500 mgld witha historyof concentrations in the therapeutic range.Unbound phenytoinconcentrations were not analyzedprior to hospitaladmission. This patient was also stabilizedon a therapeuticregimenof cyclosporine. Two monthsprior to admission a renalbiopsyshowedchronictubularinterstitial and chronic vascular rejection.Cyclosporinewas discontinuedand tacrolimuswas