Phenytoin prodrug (anticonvulsant) Pregnancy: US label §8.1: in humans, prenatal exposure to phenytoin (the active metabolite of fosphenytoin) may increase the risks for congenital malformations and other adverse developmental outcomes, including an increased incidence of major malformations such as orofacial clefts and cardiac defects, and the fetal hydantoin syndrome (dysmorphic skull and facial features, nail and digit hypoplasia, growth abnormalities including microcephaly, and cognitive deficits). Several cases of malignancies, including neuroblastoma, have been reported in children of exposed mothers. Physicians are advised to recommend that pregnant patients enrol in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. (US risk-summary format; no UK SPC §4.6 was retrieved, and this section is marked truncated at the source-fetch limit.)

Fosphenytoin sodium

Brand names: Pro-Epanutin

Fosphenytoin sodium is a water-soluble phenytoin prodrug given by injection for status epilepticus and as a short-term parenteral substitute for oral phenytoin.

Adult dose

Dose: Status epilepticus (adult): loading dose 15 mg PE/kg to 20 mg PE/kg, infused at 100 mg PE/min to 150 mg PE/min. Non-emergent loading and maintenance (adult): loading dose 10 to 20 mg PE/kg given IV or IM; initial maintenance dose 4 to 6 mg PE/kg/day in divided doses.

Route: Intravenous infusion (for IV use, dilute in 5% Dextrose Injection or 0.9% Sodium Chloride Injection to a concentration of 1.5 to 25 mg PE/mL). The intramuscular route is used only for non-emergent loading — 'Fosphenytoin sodium injection should ordinarily not be given intramuscularly', and IM should ordinarily not be used in status epilepticus because therapeutic phenytoin concentrations may not be reached as quickly as with IV administration.

Frequency: A single loading dose, followed by maintenance dosing in divided doses

Max: Rate of administration must not exceed 150 mg PE/min in adults. Maximum concentration of fosphenytoin in any infusion solution is 25 mg PE/mL. No maximum total dose is stated in the retrieved sections.

PROVENANCE: no UK SPC (eMC) record was retrieved in this bundle — the regimen above is taken from the US FDA prescribing information for Fosphenytoin Sodium Injection USP (Gland Pharma Limited, label date 2023-10-17). Verify against the UK SPC before use. UNITS — CRITICAL: 'The dose, concentration, and infusion rate of fosphenytoin sodium injection should always be expressed as phenytoin sodium equivalents (PE).' There is no need to perform molecular-weight-based adjustments when converting between fosphenytoin and phenytoin sodium doses. DOSING-ERROR WARNING (§5.1): do not confuse the concentration of the vial (50 mg PE/mL) with the total amount of drug in the vial — errors, including fatal overdoses, have occurred; a 2 mL vial contains 100 mg PE and a 10 mL vial contains 500 mg PE. MONITORING: continuous monitoring of the electrocardiogram, blood pressure and respiratory function is essential because of the risk of hypotension and cardiac arrhythmias, and the patient should be observed throughout the period where maximal serum phenytoin concentrations occur, approximately 10 to 20 minutes after the end of the infusion. The full antiepileptic effect is not immediate, so other measures — usually including concomitant administration of an IV benzodiazepine — will normally be necessary to control status epilepticus. The loading dose should be followed by maintenance doses of either fosphenytoin or phenytoin. ELDERLY (§8.5): phenytoin clearance tends to decrease with increasing age; lower or less frequent dosing may be required. TRUNCATION: §2.4 is marked truncated at the source-fetch limit and §2.5-2.8 (including any hepatic/renal dosing) were NOT retrieved — do not treat the above as the complete posology.

Paediatric dose

Route: Intravenous infusion (IM should ordinarily not be used in paediatric patients)

Frequency: Single loading dose for status epilepticus; for non-emergent use, a loading dose followed by maintenance every 12 hours

Max: Infusion rate must not exceed 2 mg PE/kg/min, or 150 mg PE/min, whichever is slower (loading); for maintenance doses the rate should not exceed 1 to 2 mg PE/kg/min, or 100 mg PE/min, whichever is slower

DOSE IS EXPRESSED IN PHENYTOIN SODIUM EQUIVALENTS (mg PE), NOT PLAIN MILLIGRAMS. Ranges rather than single figures are stated (15-20 mg PE/kg for status epilepticus; 10-15 mg PE/kg for non-emergent loading), so no single dosePerKg value has been recorded. Exact US label wording — STATUS EPILEPTICUS, paediatric (birth to less than 17 years of age): 15 mg PE/kg to 20 mg PE/kg at 2 mg PE/kg/min, or 150 mg PE/min, whichever is slower. NON-EMERGENT LOADING AND MAINTENANCE, paediatric: loading dose 10 to 15 mg PE/kg at a rate of 1 to 2 mg PE/kg/min (or 150 mg PE/min, whichever is slower); initial maintenance dose 2 to 4 mg PE/kg every 12 hours at a rate of 1 to 2 mg PE/kg/min (or 100 mg PE/min, whichever is slower). Rapid intravenous administration increases the risk of adverse cardiovascular reactions. Intramuscular administration should ordinarily not be used in paediatric patients. Source is US labelling — verify against the UK SPC and a children's formulary.

Dose independently re-sourced from US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

A history of hypersensitivity to fosphenytoin sodium injection or its inactive ingredients, or to phenytoin or other hydantoins (reactions have included angioedema)
Sinus bradycardia, sino-atrial block, second and third degree A-V block, or Adams-Stokes syndrome, because of the effect of parenteral phenytoin or fosphenytoin on ventricular automaticity
A history of prior acute hepatotoxicity attributable to fosphenytoin sodium or phenytoin
Coadministration with delavirdine, because of the potential for loss of virologic response and possible resistance to delavirdine or to the class of non-nucleoside reverse transcriptase inhibitors

Side effects

Adults, incidence 10% or more: pruritus, nystagmus, dizziness, somnolence and ataxia
Paediatric patients, incidence 10% or more: vomiting, nystagmus and ataxia
Cardiovascular risk associated with rapid infusion — hypotension and cardiac arrhythmias
Serious dermatologic reactions (including SJS/TEN), DRESS/multiorgan hypersensitivity, and angioedema — discontinue at the first sign of a rash unless clearly not drug-related
Hepatic injury; haematopoietic complications; sensory disturbances; local toxicity including purple glove syndrome; exacerbation of porphyria; hyperglycaemia; withdrawal-precipitated seizure/status epilepticus on abrupt dose reduction or discontinuation

Interactions

Multiple interactions arise because phenytoin is extensively bound to serum plasma proteins and prone to competitive displacement — caution is advised when administering fosphenytoin with other drugs that significantly bind to serum albumin
Phenytoin is primarily metabolised by CYP2C9 and to a lesser extent CYP2C19 and is particularly susceptible to inhibitory drug interactions because it is subject to saturable metabolism — inhibition of metabolism may produce significant increases in circulating phenytoin concentrations and enhance the risk of toxicity
Phenytoin/fosphenytoin is a potent inducer of hepatic drug-metabolising enzymes, reducing concentrations of many co-administered drugs
Delavirdine — coadministration is contraindicated
Monitoring of phenytoin serum levels is recommended when a drug interaction is suspected. (The itemised interaction tables in §7.1-7.2 are marked truncated at the source-fetch limit and were NOT retrieved.)

Clinical monograph

How it works

It is rapidly converted to phenytoin, which blocks voltage-gated sodium channels to stabilise neuronal membranes and limit the spread of seizure activity.

Prescribing in practice

Doses are prescribed in phenytoin sodium equivalents to avoid dosing errors, and rapid administration can cause severe hypotension and cardiac arrhythmias requiring cardiac and blood-pressure monitoring.
It carries the risk of serious skin reactions and hepatotoxicity, and exhibits non-linear (saturable) pharmacokinetics shared with phenytoin.
Severe cardiovascular reactions are more likely in elderly or seriously ill patients, so the infusion rate must be controlled.

Monitoring

Continuous ECG, blood pressure and respiratory monitoring are required during and after infusion, with phenytoin plasma concentrations checked once conversion is complete.

Counselling the patient

This medicine will be given and monitored in hospital with heart-rhythm and blood-pressure observation.
The care team should report any rash, fever or yellowing of the skin promptly.
Tell staff about all other medicines, as interactions are common.

Evidence & guidelines

Fosphenytoin is an established parenteral option in status epilepticus and offers better infusion-site tolerability than intravenous phenytoin.

Reference: NICE NG217; UK status epilepticus algorithms; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways