phenytoin and theophylline

Phenytoin induces hepatic cytochrome P450 enzymes, including CYP1A2 and CYP3A4, which are responsible for the metabolism of theophylline. This induction increases theophylline clearance, leading to reduced plasma concentrations.

Theophylline therapeutic efficacy may be significantly reduced, leading to suboptimal bronchodilation and worsening of respiratory symptoms in patients with asthma or COPD. Theophylline has a narrow therapeutic index, so even modest reductions in exposure can be clinically important.

If coadministration is necessary, monitor serum theophylline concentrations closely. It may be necessary to increase the theophylline dose by 20 to 50 percent and adjust based on levels. Reassess after any change in phenytoin therapy. Alternative bronchodilators should be considered.

The interaction is well established in the literature and widely cited in drug interaction compendia. Several studies demonstrate phenytoin-induced reduction in theophylline half-life and clearance.