Unmasking the significant enzyme-inducing effects of phenytoin on serum carbamazepine concentrations during phenytoin withdrawal

OBJECTIVE: We report on two patients who appeared to exhibit profound induction of carbamazepine metabolism during cotherapy with phenytoin. Gradual withdrawal of phenytoin confirmed this impression. DESIGN: Two case studies. RESULTS: Two patients receiving carbamazepine and phenytoin as combination anticonvulsant therapy were admitted for comprehensive rehabilitation. A 23-year-old man had therapeutic serum phenytoin concentrations, but his serum carbamazepine concentrations were so low that they were nonquantifiable. Doubling the daily carbamazepine dosage did not yield quantifiable serum concentrations. When the daily phenytoin dosage was tapered from 500 to 200 mg, the carbamazepine concentration rose to 10.0 micrograms/mL. No further changes in serum carbamazepine concentrations were observed when the phenytoin was discontinued. A 49-year-old man was receiving large daily dosage of phenytoin (600 mg) and carbamazepine (2300 mg). In the process of tapering and discontinuing phenytoin, the patient became lethargic and confused. These signs and symptoms suggested carbamazepine toxicity. The patient was eventually stabilized on a carbamazepine dosage of 1200 mg/d, which produced a serum concentration of 8.4 micrograms/mL. When this patient had been receiving concurrent phenytoin therapy, approximately twice as much carbamazepine (2300 mg) was required to maintain a similar serum concentration. CONCLUSIONS: Phenytoin is a potent inducer of carbamazepine metabolism. Whenever phenytoin dosages are tapered and discontinued in patients receiving these medications concomitantly, frequent serum carbamazepine monitoring is recommended during the ensuing deinduction phase.