Theophylline-isoniazid interaction

Drugs influencing hepatic microsomal enzyme systems, such as isoniazid, may affect the elimination pattern of theophylline. The case reported here refers to an adult female patient with a history of chronic asthma and intestinal tuberculosis who, during isoniazid therapy, presented with theophylline plasma concentrations above the therapeutic range and developed toxic symptoms. The initial episode of theophylline toxicity occurred after one month of coadministering isoniazed 300 mg/d and theophylline 350 mg bid. The theophylline plasma concentration during this episode was 24.1 micrograms/mL and was associated with the typical symptoms of theophylline toxicity. Rechallenge with isoniazide 300 mg/d and theophylline 400 mg bid showed a progressive increase in trough morning theophylline plasma levels, reaching a toxic concentration of 25.1 micrograms/mL on day 55. After withdrawal of isoniazid, theophylline concentrations gradually declined, reaching 12.9 micrograms/mL in 35 days. Theophylline toxicity in this patient might have been induced by chronic administration of isoniazid.