Multiple drug interactions with phenytoin

A 49-year-old female with chronic alcoholism and epilepsy, treated with phenytoin, began to convulse when treatment with disulfiram (an inhibitor of phenytoin metabolism) was discontinued. The patient at this stage was resistant to the large doses of phenytoin, apparently owing to induction of the metabolism of this drug by chronic alcohol intake. Later, a small (30%) increase in dose resulted in about a tenfold increase in plasma concentration of phenytoin and severe toxicity. The final dose of phenytoin required to maintain the plasma level within the therapeutic range suggested that the enzyme induction had decreased. The value of monitoring plasma concentrations of phenytoin is emphasized.