Toxic interaction between fluvoxamine and sustained release theophylline in an 11-year-old boy

An 11-year-old boy with asthma had been receiving a controlled release theophylline preparation. He was prescribed fluvoxamine for a depressive disorder and within a week complained of severe headaches, tiredness and vomiting. His serum theophylline concentration had increased from 14.2 mg/L (shortly before fluvoxamine was started) to 27.4 mg/L. Fluvoxamine was withdrawn and theophylline concentrations decreased. Clomipramine was substituted for fluvoxamine with no further problems, and a later theophylline concentration was 13.7 mg/L. Competitive inhibition of hepatic microsomal enzymes by fluvoxamine may have been responsible for the elevated theophylline concentrations and toxicity observed in this case.