Antipyretic analgesics in patients on antiepileptic drug therapy

The effect of administration for three days of acetylsalicylic acid (1500 mg/day), phenylbutazone (300 mg/day), paracetamol (1500 mg/day) and tolfenamic acid (300 mg/day) on serum concentrations of phenytoin and carbamazepine were studied in a group of patients on continuous antiepileptic therapy. When measured 10 h after the last dose of the analgesics, the only significant effect was a decrease in total serum phenytoin after three days of phenylbutazone. When six patients on continuous phenytoin therapy took phenylbutazone for two weeks there was at two days an initial decrease, followed by a signficiant increase in total serum phenytoin and a concomitant increase in free phenytoin in serum. Even phenylbutazone was well tolerated by most of the patients. However, its use had to be discontinued on one patient due to obvious signs of phenytoin intoxication, with concomitant increases in the serum free and total phenytoin concentrations.