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[Pharmacology](https://durgical.com/en/pharmacology/) · [Antiseizure medicines](https://durgical.com/en/pharmacology/classes/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

- Class: [Antiseizure medicines](https://durgical.com/en/pharmacology/classes/antiseizure-medicines/)
- Ion channel: Voltage-gated sodium channel (Nav), through phenytoin
- ATC code: N03AB05

## 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 →](https://durgical.com/en/conditions/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

### Serious (rare, important)

- Severe hypotension and arrhythmias with fast infusion
- Purple glove syndrome (swelling, discolouration and pain distal to the injection site)
- Serious skin reactions and DRESS
- Liver injury

## 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.

## Memory aid

Fosphenytoin: «PE, please» – always dose in phenytoin equivalents and never rush the drip.

## 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.

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## Related drugs

- [Phenytoin](https://durgical.com/en/pharmacology/phenytoin/)

## Related conditions

- [Epilepsy and seizures](https://durgical.com/en/conditions/epilepsy-and-seizures/)

[← Back to the class: Antiseizure medicines](https://durgical.com/en/pharmacology/classes/antiseizure-medicines/)

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](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb38bc6a-99c7-4cda-b3f0-37f629d060cf) (DailyMed (U.S. National Library of Medicine), 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=N03AB05) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/pharmacology/fosphenytoin/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/fosphenytoin/