Toxic effects may occur with only small increments in dose
Sulfonamides can displace phenytoin from its binding sites, increasing the plasma-free fraction of the drug. Induction of liver drug-metabolizing enzymes by phenobarbital results in a decreased half-life of phenytoin, and isoniazid increases plasma levels of phenytoin by inhibiting its metabolism. Because of the dose-dependent elimination kinetics of phenytoin, some toxicity may occur with only small increments in dose.
