fosphenytoin

Fosphenytoin is a water-soluble prodrug of phenytoin used as an anticonvulsant. It is administered parenterally (intravenous or intramuscular) and is converted rapidly in the body to phenytoin by tissue alkaline phosphatases. The drug is supplied and dosed in phenytoin equivalents (PE), reflecting its conversion to active phenytoin. A brand form, Cerebyx, is commonly used in clinical practice.

Pharmacology and pharmacokinetics are characterized by the action of phenytoin on neuronal membranes through blockade of voltage-gated sodium channels, stabilizing hyperexcitable membranes and limiting seizure activity. Fosphenytoin provides more predictable absorption and fewer local reactions than intravenous phenytoin. After conversion, phenytoin exhibits nonlinear pharmacokinetics with high protein binding and wide interindividual variability, requiring monitoring of serum levels and clinical status.

Indications include treatment and prevention of tonic-clonic seizures and the management of convulsive status epilepticus when IV access is needed or during rapid seizure control. It is particularly favored for IV administration due to reduced local irritation compared with phenytoin; it is not given orally in routine practice, where phenytoin is used.

Dosing is expressed in phenytoin equivalents. A common loading dose is 15–20 mg PE/kg infused over about 30 minutes, with a maximum rate of 150 mg PE/min. Maintenance dosing typically ranges from 4–6 mg PE/kg/day in divided doses, adjusted by clinical response and serum levels. Therapeutic concentration targets are usually expressed as total phenytoin levels of roughly 10–20 μg/mL.

Adverse effects resemble those of phenytoin and include hypotension or arrhythmias if infused too rapidly, CNS events (dizziness, ataxia), rash, gingival hyperplasia, and potential hepatotoxicity. Fosphenytoin interacts with many drugs via hepatic enzyme induction and altered protein binding, and dosing should be individualized in liver disease or during pregnancy.