Drug reference

Phenytoin

Antiepileptic

Also known as Phenytoin Sodium, Diphenylhydantoin, Eptoin, Dilantin

START

Load 15-20 mg/kg IV at ≤50 mg/min (or fosphenytoin), then maintenance 3-5 mg/kg/day PO divided BID-TID

TYPICAL MAX

individualized — target free phenytoin 1-2 µg/mL (or total 10-20 if albumin normal)

STOP IF

Hypersensitivity · sinus bradycardia · 2°-3° AV block · porphyria

WATCH

Levels · CBC · LFTs · gum hyperplasia · ataxia/nystagmus · skin rash

CDSCO approvedSchedule HJan AushadhiNPPA price-controlledATC N03AB02

Dose laddermg/d

Renal dose adjustmenteGFR mL/min/1.73m²

KDIGO 2024 + manufacturer label

Pharmacokineticsplasma · t hours

ONSET: 1h · PO onset; IV peak within hour
PEAK: 4h · PO Cmax
t½: 22h · plasma t½ (Michaelis-Menten — dose-dependent)
DURATION: 1d · BID-TID dosing window

EXCRETION

Hepatic CYP2C9/2C19 · saturable (Michaelis-Menten)

route + CYP

INTERACTIONS

12 major

SEVERE in our sources

PREGNANCY

Category D — fetal hydantoin syndrome; folate supplementation 5 mg/d pre-conception

FDA category + note

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Available in India

106 branded formulations and 24 fixed-dose combinations. Look up specific brands in the Drugs workspace.

Jan Aushadhi — generic available at GoI pharmacies

Mechanism

Phenytoin stabilizes neuronal membranes and reduces seizure propagation by modulating voltage-gated sodium channels, thereby inhibiting repetitive firing of action potentials. It also enhances the efflux of sodium ions from neurons and influences calcium channels, contributing to its antiseizure effects.

Indications

Generalized tonic-clonic seizures (Grand Mal)Complex partial seizures (Psychomotor or Temporal Lobe)Prevention and treatment of seizures during or after neurosurgeryStatus epilepticus (IV administration)Trigeminal neuralgia (off-label)focal epilepsystatus epilepticusfocal seizures with and without tonic-clonic generalizationEpilepsygeneralized tonic-clonic seizuressimple partial seizurescomplex partial seizurestrigeminal neuralgia (second choice)status epilepticus (occasionally, but fosphenytoin has replaced it)

Dosing

Adult: Oral: Initial 100 mg 2-3 times daily, may increase to 300-400 mg daily in 2-3 divided doses. IV: Loading dose of 15-20 mg/kg infused at 50 mg/min, followed by maintenance 100 mg orally or IV every 6-8 hours (or 5 mg/kg/day in 2-3 divided doses).
Pediatric: Oral: Initial 5 mg/kg/day in 2-3 divided doses; maintenance 4-8 mg/kg/day. IV: Loading dose of 15-20 mg/kg infused at 1-3 mg/kg/min, followed by maintenance 5-7 mg/kg/day in 2-3 divided doses.
Renal adjustment: No specific dose adjustment for renal impairment, but careful monitoring of plasma phenytoin concentrations is recommended due to altered protein binding in uremia. Use lower end of dosing range and titrate based on response and levels. Unbound phenytoin levels may be more accurate in severe renal dysfunction.…
Max dose: 400 mg/day

Pharmacokinetics

Onset

IV: 30-60 minutes; Oral: 2-24 hours (variable due to absorption)

Peak effect

Oral: 3-12 hours (standard capsules), 4-24 hours (extended-release); IV: 20-30 minutes after completion of infusion

Duration

Variable, typically 12-24 hours depending on dose and metabolism

Half-life

Dose-dependent, 7-42 hours (average approximately 22 hours)

Bioavailability

Highly variable, ~70-90% (oral)

Protein binding

~90% (primarily to albumin)

Metabolism

Primarily hepatic metabolism via cytochrome P450 enzymes (CYP2C9 and CYP2C19), exhibits saturable (non-linear) kinetics

Excretion

Mainly renal excretion of inactive metabolites (approximately 95%)

Contraindications

Hypersensitivity to phenytoin or other hydantoins
Sinus bradycardia
Sinoatrial block
Second-degree and third-degree atrioventricular (AV) block
Adams-Stokes syndrome
History of acute hepatic porphyria
absence seizures

Side effects

Common

NystagmusAtaxiaSlurred speechConfusionGingival hyperplasiaHirsutismRash (morbilliform)NauseaVomitingConstipationDizzinessHeadacheTremorInsomniaOsteoporosis (with long-term use)gum hypertrophy (20% incidence, more in younger patients, due to overgrowth of gingival collagen fibres)coarsening of facial featuresacneepigastric painvomiting (minimized by taking drug with meals)

Serious

Stevens-Johnson syndrome (SJS)
Toxic epidermal necrolysis (TEN)
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome
Hepatotoxicity
Aplastic anemia
Leukopenia
Thrombocytopenia
Cardiac arrhythmias (with rapid IV infusion, especially bradycardia, hypotension, AV block)
Purple glove syndrome (with IV extravasation)
Lymphadenopathy
Folate deficiency
Pseudolymphoma
Peripheral neuropathy (with long-term use)
Hypersensitivity reactions
Fatal skin reactions
toxicity (due to accumulation and narrow therapeutic range)
Stevens-Johnson syndrome
toxic epidermal necrolysis
toxicity at usual doses (due to inability to hydroxylate)
hypoplastic phalanges (teratogenic)
cleft lip/palate (teratogenic)
microcephaly (teratogenic)
ataxia
vertigo
diplopia
nystagmus (cerebellar and vestibular manifestations, at high plasma levels)
drowsiness
behavioral alterations
mental confusion
hallucinations
disorientation
rigidity (at high plasma levels)
rashes
DLE
lymphadenopathy (hypersensitivity reactions)
neutropenia (rare, requires discontinuation)
megaloblastic anaemia (decreases folate absorption and increases excretion)
osteomalacia (interferes with metabolic activation of vit D and with calcium absorption/metabolism)
inhibition of insulin release and hyperglycaemia
foetal hydantoin syndrome (hypoplastic phalanges, cleft palate, hare lip, microcephaly) if used during pregnancy
local vascular injury (intimal damage, thrombosis of the vein, edema, discolouration) with IV injection if rate exceeds 50 mg/min or extravasation occurs
fall in BP and cardiac arrhythmias with IV injection (requires continuous ECG monitoring)

Pregnancy & lactation

Pregnancy

Category D — fetal hydantoin syndrome; folate supplementation 5 mg/d pre-conception

Lactation

Phenytoin is excreted into breast milk. Monitor breastfed infants for sedation, feeding difficulties, poor weight gain, and jaundice. The amount transferred is relatively small, but caution is advised, and the lowest effective dose should be used. Consider monitoring infant plasma levels in specific cases.