Double-blind randomized study comparing brand-name and generic phenytoin monotherapy.

Ten patients with well-controlled seizures receiving chronic phenytoin (PHT) monotherapy for seizure prophylaxis completed a randomized double-blind crossover study comparing brand-name and generic PHT. Each patient received the same dose of each preparation for 3 months during which trough PHT concentrations and adverse effects were monitored. The average predose steady-state total PHT concentration was 11.9 +/- 4.9 micrograms/ml during brand-name therapy and 14.2 +/- 8.2 micrograms/ml during generic therapy. The average predose steady-state free PHT concentrations were 0.93 +/- 0.47 micrograms/ml (brand name) and 1.14 +/- 0.64 micrograms/ml (generic), respectively (p less than 0.005). The potency (capsule content) values for the lots used in the study were 99.2% for the brand-name and 104.6% for generic. Because of the nonlinear Michaelis-Menten kinetics of PHT, a 5.4% difference in potency could account for the observed differences in plasma concentrations. When compared with brand-name PHT therapy, the generic drug was associated with an increase in serum concentration. This increase was consistent with the reported difference in capsule content between the generic and brand-name lots used in this study.

RCT Entities:   Population Interventions Outcomes