Predisposing factors to apparent theophylline-induced seizures

Fifteen patients experienced theophylline-related seizures at our institution over the past 3 years. Thirteen of the patients were receiving oral maintenance theophylline therapy while two patients were on IV therapy at the time of their episode. The serum theophylline concentration (STC) obtained 1.8 +/- 1.5 hours after the seizure was 26 +/- 11 micrograms/mL, although this level was not obtained until 5.2 +/- 2 hours after the last oral dose. Factors potentially decreasing theophylline metabolism (URI, abnormal liver functions, cimetidine therapy) were noted in 11/15 (73%) of the patients. This varied significantly from a control group of asymptomatic patients (P less than .01). Ten of thirteen patients on oral therapy were receiving solid-dose theophylline prescriptions over 17 mg/kg/day and differed from the control group (19 +/- 8 v 14 +/- 4, P less than .01). An abnormal neurologic history, brain scan, or head CT was noted in 11/15 (73%); however, there was no acute mortality or neurologic morbidity noted in this series. The clinical features of our patients differed from previously reported cases with respect to a lower STC, higher incidence of underlying CNS problems, higher percentage of patients on oral therapy, and the absence of serious morbidity or mortality.