carbamazepine and theophylline

Carbamazepine is a potent inducer of hepatic cytochrome P450 enzymes, including CYP1A2, CYP3A4 and CYP2E1. Theophylline is predominantly metabolised by CYP1A2, with minor contributions from CYP3A4 and CYP2E1. Induction of these enzymes by carbamazepine increases the rate of theophylline metabolism, leading to lower plasma concentrations of theophylline.

Concurrent use can significantly reduce theophylline plasma concentrations, potentially resulting in loss of therapeutic effect, such as worsening of asthma or chronic obstructive pulmonary disease symptoms. Conversely, if carbamazepine is discontinued, enzyme induction subsides and theophylline concentrations can rise, leading to toxicity including nausea, vomiting, cardiac arrhythmias and seizures.

Monitor serum theophylline concentrations before and after starting or stopping carbamazepine. Adjust the theophylline dose as necessary to maintain therapeutic concentrations and clinical response. Continue monitoring until concentrations are stable. Advise patients to report signs of worsening respiratory symptoms or theophylline toxicity.

Well established in clinical practice and supported by pharmacokinetic studies. The interaction is predictable and clinically significant.