VENOUS IRRITATION RELATED TO INTRAVENOUS ADMINISTRATION OF PHENYTOIN VERSUS FOSPHENYTOIN

Study Objective. To compare the frequency severity, and time course of venous irritation after administration of a single intravenous dose o f phenytoin with an equimolar dose of fosphenytoin, a water-soluble ph enytoin prodrug. Design. Randomized, double-blind, two-period, crossov er study. Setting. University hospital clinical research unit. Patient s. Twelve healthy volunteers within 15% of ideal body weight and with no clinically significant abnormalities on physical examination, medic al history, or laboratory assessment. Interventions. Volunteers random ly received a 30-minute infusion of phenytoin sodium 250 mg (250 mg/5 mi) or an equimolar dose of fosphenytoin 375 mg (375 mg/5 mi). Subject s returned for the crossover treatment 14-21 days later. Measurements and Main Results. Subjects assessed venous irritation (pain, burning, itching), and investigators evaluated phlebitis (erythema, swelling, t enderness), induration, exudation, and cording. Phenytoin was associat ed with a significantly higher degree of pain at the infusion site in all subjects and a significant degree of phlebitis in eight subjects ( p<0.05); cording occurred in six subjects. The time course of phenytoi n-induced phlebitis was bimodal. Erythema and tenderness were prominen t at the end of the infusion and again at 24 hours. Cording was first noted between 24 hours and 1 week after infusion. In contrast, fosphen ytoin was associated with mild pain in two subjects, one incident of p hlebitis, and no erythema or cording. Conclusions. Fosphenytoin admini stration resulted in significantly less venous irritation and phlebiti s compared with an equimolar dose of phenytoin. The clinical use of th is water-soluble phenytoin prodrug should minimize the frequency and s everity of infusion-site reactions and should allow convenient, rapid, intravenous administration of drug, undiluted or admired with intrave nous solutions.