The pharmacokinetics, safety, and tolerability of fosphenytoin in children from 1 day to 16 years old and the data available from 78 patients in two multicenter studies are reviewed from the Medical College of Virginia Commonwealth University, Richmond, VA. The conversion half-life of fosphenytoin to phenytoin following intravenous administration in 62 patients was 8.3 min (range, 2.5-18.5 min), with no relation to age. Plasma total phenytoin concentrations of 10-40 mcg/ml were obtained by 15 min. In 16 patients receiving intramuscular fosphenytoin, 5.5 mL, plasma total phenytoin concentrations of 10 mcg/mL were reached within 20 min. The equivalent plasma free phenytoin concentration was 1 mcg/mL. IV infusion rates were 0.5-3 mg PE/kg/min. IM loading doses ranged from 12-20 mg PE/kg, administered in one to three sites. Mild bruising, tenderness, swelling, and/or erythema occurred at infusion or injection sites in 3 (6%) of 52 patients with adequate records. Common systemic reactions included emesis, nystagmus, ataxia, and pruritus. [1]

COMMENT. The advantages of fosphenytoin over phenytoin for parenteral administration include a pH closer to neutral, solubility and compatibility with intravenous fluids, and less discomfort and adverse reaction. The higher cost of fosphenytoin cf phenytoin is offset by the lower rates of complications and outcome expenses. Serious reactions, such as purple glove syndrome, have not been reported with IV fosphenytoin.

Purple glove syndrome with IV phenytoin is reported in 5.9% of 152 adult patients treated in a 3-month period at the Mayo Clinic [2]. Purple glove syndrome (PGS) is a progressive development of edema, discoloration, and pain after IV phenytoin. Elderly patients and those receiving large, multiple doses are particularly at risk. Most patients respond to conservative therapy.