Antiepileptic (sodium channel blocker) Pregnancy: Phenytoin crosses the placenta and may cause foetal harm; associated with ~6% frequency of major malformations (vs 2-3% background) and Foetal Hydantoin Syndrome. Should not be used during pregnancy unless the benefit outweighs the risks after considering alternatives; women of childbearing potential must use effective contraception.

Phenytoin

Brand names: Epanutin

Used in: Head Injury Seizures & Epilepsy

Phenytoin is an older antiepileptic still important for status epilepticus and some seizures; it needs careful handling because of its pharmacokinetics.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: Initially 3-4 mg/kg/day; maintenance 200-500 mg daily

Route: Oral

Frequency: Single or divided doses

Max: For most adults a satisfactory maintenance dose is 200-500 mg daily; exceptionally a dose outside this range may be indicated

For seizures: introduce in small dosages with gradual increments until control is achieved; dosage individualised as serum levels vary widely with equivalent doses. Clinically effective serum level is usually 10-20 mg/l (40-80 micromoles/l). Do not change dosage at intervals shorter than 7-10 days (time to steady state). Trigeminal neuralgia: 300-500 mg in divided daily doses (total phenytoin levels should not exceed 20 mcg/ml). Elderly (over 65): clearance decreased - lower or less frequent dosing may be required. Oral administration only. 100 mg phenytoin sodium is equivalent to 92 mg phenytoin; care needed when changing dosage form.

Paediatric dose

Dose: 5 mg/kg

Route: Oral

Frequency: Daily in two divided doses (initial dose)

Max: 300 mg daily

Infants and children: initially 5 mg/kg/day in two divided doses, subsequently individualised to a maximum of 300 mg daily; usual recommended maintenance 4-8 mg/kg/day. Neonates: oral absorption is unpredictable and metabolism may be depressed - it is especially important to monitor serum levels.

Dose adjustments

Renal

In renal or hepatic disease, or with hypoalbuminaemia, the unbound fraction of phenytoin is increased - interpret total plasma concentrations with caution; unbound (free) phenytoin concentrations may be more useful.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Paediatric weight-based calculator

Patient weight (kg)

Verify in a children's formulary

US labelling (FDA)

Reference — US labelling, may differ from UK

For Status Epilepticus and Non-emergent Loading Dose: Adult loading dose is 10 to 15 mg/kg at a rate not exceeding 50 mg/min. ( 2.2 ) Pediatric loading dose is 15 to 20 mg/kg at a rate not exceeding 1 to 3 mg/kg/min or 50 mg/min, whichever is slower. ( 2.8 ) Continuous monitoring of the electrocardiogram, blood pressure, and respiratory function is essential. ( 2.2 ) Maintenance Dosing: Initial loading dose should be followed by maintenance doses of oral or intravenous Phenytoin Sodium Injection every 6 to 8 hours. ( 2.2 , 2.3 ) Intramuscular Administration: Because of erratic absorption and local toxicity, Phenytoin Sodium Injection should ordinarily not be given intramuscularly. ( 2.2 , …

Source: US FDA prescribing information (openFDA / DailyMed), label dated 2024-04-09. Accessed 2026-06-12. US dosing and indications can differ from UK practice — use UK sources for prescribing decisions.

Contraindications

Hypersensitivity to phenytoin, to any of the excipients, or to other hydantoins

Side effects

CNS (usually dose-related): nystagmus, ataxia, slurred speech, decreased co-ordination, mental confusion, dizziness, headache, somnolence
Gastrointestinal: nausea, vomiting, constipation
Skin: morbilliform rash; serious/fatal reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, AGEP
Connective tissue: gingival hyperplasia, coarsening of facial features, hirsutism (rare)
Haematological (some fatal): thrombocytopenia, leucopenia, agranulocytosis, pancytopenia, megaloblastic anaemia; hepatotoxicity; HSS/DRESS; anaphylaxis

Interactions

St John's wort (Hypericum perforatum): decreased plasma phenytoin concentrations and reduced clinical effect - should not be used with phenytoin
Hormonal contraceptives: enzyme induction may cause failure of contraceptive effect - use additional/alternative effective contraception
Phenytoin is a potent inducer of hepatic enzymes and is subject to saturable metabolism; monitor serum levels when a drug interaction is suspected

Clinical monograph

How it works

It blocks voltage-gated sodium channels, stabilising hyperexcitable neuronal membranes.

Prescribing in practice

It has a narrow therapeutic index with saturable (zero-order) kinetics — small dose changes can cause large swings in level, so titrate against plasma levels (interpreted with albumin).
It is a potent enzyme inducer with many interactions, including reducing the effectiveness of hormonal contraception.
Intravenous use requires cardiac monitoring and a slow rate (risk of hypotension/arrhythmia) and causes severe tissue injury if it extravasates; long-term effects include gum overgrowth, hirsutism and neuropathy, and it is teratogenic.

Monitoring

Monitor plasma phenytoin levels (adjusted for albumin), ECG/blood pressure during IV use, and FBC/LFTs long-term.

Counselling the patient

Stay on the same brand/formulation, and attend for blood-level checks.
Report any rash promptly (stop and seek advice — serious skin reactions can occur), or gum swelling or unsteadiness.
It makes the contraceptive pill less effective.

Evidence & guidelines

Established for status epilepticus and epilepsy, used with plasma-level monitoring (NICE NG217).

Reference: NICE CG137 Epilepsies; 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

Drugs

Eslicarbazepine acetate · Antiepileptic (sodium channel blocker)

Pathways