BACKGROUND:Safety, tolerability, and pharmacokinetics of fosphenytoin sodium, a water-soluble phenytoin prodrug, were investigated after a temporary substitution of intramuscular fosphenytoin for oral phenytoin sodium in 240 epileptic or neurosurgical patients taking oralphenytoin sodium (100-500 mg/d). METHODS: Patients were randomly assigned to 1 of 2 parallel groups. During screening and follow-up, patients were maintained on a regimen of oral phenytoin at an individualized dose. During treatment, the phenytoin-treated patients received intramuscular placebo and their prescribed dose of oral phenytoin; the fosphenytoin-treated patients received oral placebo and intramuscular fosphenytoin equimolar to their phenytoin dose. RESULTS: Both groups had similar types and frequencies of mild to moderate adverse events. Fosphenytoin was as well tolerated as intramuscular placebo at the injection site. Intramuscular fosphenytoin equimolar to a patient's oral phenytoin dose produced equal or greater plasma phenytoin concentrations. CONCLUSIONS: Dosing adjustments are not required when intramuscular fosphenytoin is temporarily substituted or oral phenytoin therapy is resumed. Intramuscular fosphenytoin is a safe and well-tolerated alternative to oral phenytoin when oral administration is not feasible.
RCT Entities:
BACKGROUND: Safety, tolerability, and pharmacokinetics of fosphenytoin sodium, a water-soluble phenytoin prodrug, were investigated after a temporary substitution of intramuscular fosphenytoin for oral phenytoin sodium in 240 epileptic or neurosurgical patients taking oral phenytoin sodium (100-500 mg/d). METHODS:Patients were randomly assigned to 1 of 2 parallel groups. During screening and follow-up, patients were maintained on a regimen of oral phenytoin at an individualized dose. During treatment, the phenytoin-treated patients received intramuscular placebo and their prescribed dose of oral phenytoin; the fosphenytoin-treated patients received oral placebo and intramuscular fosphenytoin equimolar to their phenytoin dose. RESULTS: Both groups had similar types and frequencies of mild to moderate adverse events. Fosphenytoin was as well tolerated as intramuscular placebo at the injection site. Intramuscular fosphenytoin equimolar to a patient's oral phenytoin dose produced equal or greater plasma phenytoin concentrations. CONCLUSIONS: Dosing adjustments are not required when intramuscular fosphenytoin is temporarily substituted or oral phenytoin therapy is resumed. Intramuscular fosphenytoin is a safe and well-tolerated alternative to oral phenytoin when oral administration is not feasible.