Reversal by phenytoin of carbamazepine-induced water intoxication: a pharmacokinetic interaction.

The hypothesis that phenytoin may antagonise the antidiuretic effect of carbamazepine has been examined by comparing the free water clearance response to a standard water load in 36 patients stabilised on different drug regimes. The diuretic response to the water load was significantly greater in patients receiving chronic treatment with carbamazepine and phenytoin in combination than in matched control subjects receiving carbamazepine as a single drug. Acute administration of phenytoin (1,100 mg), however, had no significant influence on carbamazepine-induced antidiuresis. Evidence is presented that reversal of the antidiuretic effect of carbamazepine by chronic phenytoin administration is secondary to a marked reduction of the serum carbamazepine concentration during combined therapy. These results suggest that the risk of developing water intoxication is greater in patients receiving carbamazepine alone than in those receiving phenytoin in combination. Since the antidiuretic effect is correlated with the serum carbamazepine concentration rather than with the prescribed daily dose, monitoring the serum level of the drug is likely to provide the best rational approach to the prevention of excessive water retention.