The Impact of Standard Versus Weight-Based Maintenance Dosing of Fosphenytoin on Achieving Therapeutic Drug Levels.

Background: Fosphenytoin is an antiepileptic drug (AED) used for the treatment of many seizure subtypes as well as seizure prophylaxis. Dosing of fosphenytoin has traditionally been weight-based, however, there is data to support standard dosing, making the optimal dosing strategy unclear. The purpose of this study was to evaluate the impact of standard versus weight-based maintenance dosing of fosphenytoin on achieving therapeutic serum phenytoin levels.

Methods: This was a retrospective review of patients admitted at two medical centers between January 1, 2021, and October 31, 2023 who received fosphenytoin maintenance therapy. Patients were divided into two groups based on initial maintenance dose: standard dosing (100 mg every 8 h) and weight-based dosing. The primary outcome was the incidence of the first serum phenytoin level being therapeutic.

Results: A total of 92 patients with an average age of 56.9 years were included, 47 patients in the weight-based dosing group and 45 patients in the standard dosing group. The mean corrected total and free phenytoin levels were 12.8 and 1.6 mcg/mL respectively in the weight-based dosing group compared to 12.1 and 1.45 mcg/mL in the standard dosing group. A total of 32 patients in the weight-based dosing group had a therapeutic level compared to 25 patients in the standard dosing group, which was not significantly different (68% versus 55.6%, P =  0.283).

Conclusion: This study found no difference in the incidence of first serum phenytoin level being therapeutic based on fosphenytoin dosing strategy utilized. Further prospective studies should be conducted to evaluate fosphenytoin maintenance dosing strategies.