Safety and tolerance of multiple doses of intramuscular fosphenytoin substituted for oral phenytoin in epilepsy or neurosurgery
B. J. Wilder, K. Campbell, R. E. Ramsay, W. R. Garnett, J. M. Pellock, S. A. Henkin and A. R. Kugler
Department of Neurology, Veterans Affairs Medical Center, Gainesville, Fla, USA.
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.
