Section 01 · Monograph

Fosphenytoin

Reviewed Nov 2026FDA label

CerebyxNa+ channel blocker (prodrug)

Black Box Warning

Cardiovascular risk with rapid infusion — severe hypotension and cardiac arrhythmias have been reported; do not exceed the maximum recommended infusion rate, and provide continuous ECG, blood pressure, and respiratory monitoring during and after infusion

Treatment of generalized convulsive status epilepticusFDA-labeled
Prevention and treatment of seizures occurring during neurosurgeryFDA-labeled
Short-term substitution for oral phenytoin when oral administration is not possibleFDA-labeled

Water-soluble phosphate ester prodrug rapidly converted to phenytoin by phosphatases in blood and tissue (conversion half-life ~8–15 minutes)
Once converted, shares phenytoin's mechanism: use-dependent blockade of voltage-gated sodium channels stabilizing neuronal membranes

Always prescribed and dosed in phenytoin sodium equivalents (PE) to avoid confusion with phenytoin dosing errors
Status epilepticus: 15–20mg PE/kg IV at 100–150mg PE/min in adults
Non-emergent loading: 10–20mg PE/kg IV or IM
Maintenance: approximately 4–6mg PE/kg/day
Unlike phenytoin, can be given intramuscularly for non-emergent situations
Requires continuous ECG, blood pressure, and respiratory monitoring during infusion and for roughly 10–20 minutes afterward, until peak phenytoin concentration is reached

Maximum adult IV infusion rate is 150mg PE/min; pediatric rates are weight-based and slower

Hypersensitivity to fosphenytoin, phenytoin, or other hydantoins
Sinus bradycardia, sinoatrial block, second- or third-degree AV block, or Adams-Stokes syndrome
Prior history of acute hepatotoxicity attributed to phenytoin/fosphenytoin
Concurrent use with delavirdine

Once converted to phenytoin, shares its interaction profile: CYP2C9/CYP2C19 substrate and strong hepatic enzyme inducer
Reduces efficacy of warfarin, hormonal contraceptives, corticosteroids, and many antiretrovirals
Contraindicated with delavirdine

Paresthesia and pruritus (notably in the groin) — common during or immediately after infusion, typically self-limited
Nystagmus, dizziness, somnolence, ataxia
Hypotension and cardiac arrhythmia with rapid infusion
Lower risk of purple glove syndrome and local injection-site reactions than IV phenytoin, owing to its water solubility
Rare but serious: Stevens-Johnson syndrome/TEN, DRESS, hepatotoxicity, blood dyscrasias (as with phenytoin)

Continuous ECG, blood pressure, and respiratory monitoring during and after infusion
Serum phenytoin concentration (fosphenytoin is fully converted before assay is meaningful — allow appropriate time post-infusion before drawing a level)
CBC, liver function, and albumin with chronic conversion to oral phenytoin

Shares phenytoin's pregnancy risk profile, including fetal hydantoin syndrome
Maternal and neonatal vitamin K supplementation used to reduce neonatal hemorrhagic risk