Pharmacology · Antiseizure medicines
Fosphenytoin !
A water-soluble prodrug of phenytoin for intravenous or intramuscular use in status epilepticus. Infusing it too fast can cause hypotension and arrhythmias.
Updated 2026-11-01
Mechanism of action
Fosphenytoin itself is inactive. Phosphatases convert it to phenytoin, which blocks voltage-gated sodium channels and stops sustained high-frequency neuronal firing. Because it dissolves in water, it can be given intravenously or intramuscularly with less local injury than phenytoin.
- Injected intravenously or intramuscularly
- Phosphatases convert it to phenytoin
- Phenytoin blocks voltage-gated sodium channels
- Sustained seizure firing stops
Pharmacokinetics
- Distribution
- Highly bound to albumin; it displaces phenytoin from binding sites
- Metabolism
- Completely converted to phenytoin after intravenous use
- Half-life
- Conversion half-life about 15 minutes; then the half-life of phenytoin
Indications
- Generalized tonic-clonic status epilepticus Epilepsy and seizures →
- Prevention and treatment of seizures during neurosurgery
- Short-term substitute for oral phenytoin when the oral route is not possible
Adverse effects
Common
- Itching, burning or tingling, often in the groin, during infusion
- Dizziness, nystagmus and unsteadiness
- Drowsiness
- Low blood pressure
Contraindications
- Hypersensitivity to fosphenytoin, phenytoin or other hydantoins
- Sinus bradycardia, sinoatrial block, second- or third-degree AV block or Adams-Stokes syndrome
- Previous liver injury caused by fosphenytoin or phenytoin
Key interactions
- The same drugs as phenytoin (CYP2C9/CYP2C19 inhibitors, enzyme-induced drugs, hormonal contraceptives)
- Same interactions as phenytoin once converted
- Highly protein-bound drugs
- Displacement and changes in free phenytoin
What is monitored
- Continuous ECG, blood pressure and breathing during and after intravenous infusion
- Phenytoin level after conversion is complete
- Infusion site
- Free phenytoin level in low albumin or kidney failure
Administration and safety
- Doses are written as phenytoin sodium equivalents (PE); mixing up PE and milligrams of fosphenytoin has caused serious dosing errors
- The intravenous infusion rate has a strict upper limit because of hypotension and arrhythmias
- Can also be given intramuscularly
- Check the vial concentration carefully before preparing
Nursing care
- Monitor ECG, blood pressure and breathing throughout the infusion and afterwards
- Slow or stop the infusion and call for help if hypotension or arrhythmia appears
- Warn the patient that itching or burning may occur during infusion
- Inspect the injection site for swelling, colour change or pain
Pregnancy and breastfeeding
As for phenytoin: linked to malformations and to the fetal hydantoin syndrome; used in status epilepticus when the benefit outweighs the risk.
Test yourself
Think of the answer, then tap the question to see it.
What is fosphenytoin and why was it developed?
A water-soluble phosphate prodrug of phenytoin, developed because phenytoin dissolves poorly in water and is hard to give by injection.
What is the main risk of infusing fosphenytoin too fast?
Severe hypotension and cardiac arrhythmias; continuous cardiac monitoring is needed during and after the infusion.
In what units are fosphenytoin doses expressed, and why does it matter?
In phenytoin sodium equivalents (PE). Confusing PE with milligrams of fosphenytoin has caused serious overdoses and underdoses.
Related drugs
Related conditions
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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - FOSPHENYTOIN SODIUM injection, solution (DailyMed (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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