Effect of over-the-counter cimetidine on phenytoin concentrations in patients with seizures

OBJECTIVE: TO determine the effects of the maximum recommended over-the-cou nter (OTC) cimetidine dosage on phenytoin concentrations in ambulatory seiz ure patients on long-term phenytoin therapy. METHODS: Adults with seizure disorders requiring phenytoin therapy were rec ruited. Trough total phenytoin concentrations were measured initially and o nce weekly for six weeks. Ail assays were performed using Biotrack patient- side cartridges. After a two-week baseline period patients took cimetidine 200 mg twice daily for two weeks. Toxicity was monitored via weekly neurolo gic examinations and midweek telephone surveys. Patients were asked to retu rn to clinic weekly during a two-week cimetidine washout period. RESULTS: Nine patients entered and completed the study. All but two patient s took other anticonvulsants: known to interact with phenytoin (carbamazepi ne, n = 5; phenobarbital, n = 2). No adverse effects or changes in seizure frequency were reported. Paired Student's t-tests revealed no significant d ifference between serum phenytoin concentrations before (12.3 +/- 3.2 mg/L [mean +/- SD]) and after (12.8 +/- 4.0 mg/L) two weeks on the OTC cimetidin e regimen. No differences were noted in estimated pharmacokinetic parameter s (maximum metabolic rate, Michaelis-Menten constant) for the same time per iods (paired Student's t-test, p > 0.05). The Biotrack assay had an r(2) = 0.7311 (p < 0.001, two-sided) when compared with TDx. CONCLUSIONS: It is possible that the lack of change in phenytoin concentrat ions was a result of the low daily dosage of cimetidine used or other facto rs related to the "real world" setting of the study. However, the potential for a serious drug interaction occurring in patients taking long-term oral phenytoin and OTC cimetidine appears to be small.