Mild theophylline-related adverse reactions and serum theophylline concentration

The relationship between theophylline-associated adverse drug reactions (ADRs) and serum theophylline concentration (STC) was studied. Patients with obstructive airway disease who received theophylline on the pulmonary ward of a large urban hospital over a 10-month period were included in the study. Each patient was interviewed within two hours after collection of a sample for determining STC and, without knowing the STC, the interviewer classified each patient into one of the following categories: ADR, no ADR, or indeterminant (symptoms similar to a theophylline-associated ADR but possibly caused by concomitant drugs or comorbidities). ADRs were also classified as to their severity. The interviewer identified 340 ADRs during 201 interviews of 126 patients. All but four of the ADRs were mild. In half of the interviews, patients reported at least two concurrent ADRs. Not including the indeterminant group, ADRs occurred in 69% of the patients, a much higher frequency than previously reported. The mean +/- S.D. STCs for the ADR and no-ADR groups were 6.5 +/- 1.7 and 7.7 +/- 2.0 micrograms/mL, respectively. When the indeterminant ADRs were added to the theophylline-associated ADRs, the resulting group had a mean +/- S.D. STC of 11.5 +/- 3.3 micrograms/mL. No significant association was found between STC and occurrence of ADRs. Theophylline-associated ADRs occurred more frequently than expected at STCs within and below the usually accepted therapeutic range.