Safety of fosphenytoin sodium

Abstract

Fosphenytoin sodium is reviewed, and its safety is compared with that of phenytoin. After i.v. or i.m. injection, fosphenytoin, a phenytoin prodrug, is rapidly hydrolyzed to phenytoin. Free-phenytoin concentrations equivalent to those obtained with i.v. phenytoin can be achieved with fosphenytoin given at equimolar loading doses by selecting the appropriate rate of fosphenytoin administration. Fosphenytoin can be expected to interact with the same drugs that interact with phenytoin. The dosage is expressed as phenytoin sodium equivalents (PE). The standard loading dose for adults with status epilepticus is 15-20 mg PE/kg i.v. infused at 100-150 mg/min; i.m. administration is not recommended for this condition. For nonemergency situations, a 10- to 20-mg PE/kg loading dose can be given i.v. or i.m. Fosphenytoin has advantages over phenytoin injection that are related to its greater aqueous solubility, which obviates the extreme alkalinity, propylene glycol, and ethanol needed in the injectable phenytoin formulation. Intravenous fosphenytoin has been associated with less soft-tissue injury and fewer adverse effects in general than phenytoin. Fosphenytoin, when administered i.m., is completely absorbed, is relatively well tolerated, and provides more predictable serum drug concentrations than i.m. phenytoin. Fosphenytoin offers practical and clinical advantages over i.v. phenytoin.