Section 01 · Monograph

Phenytoin

Reviewed Nov 2026FDA label

DilantinNa+ channel blocker

Black Box Warning

IV administration: rate should not exceed 50 mg/minute in adults (slower, weight-based rate in pediatric patients) — rapid infusion is associated with severe hypotension and cardiac arrhythmias, particularly in elderly or hemodynamically unstable patients; continuous ECG and blood pressure monitoring required

Control of generalized tonic-clonic (grand mal) and complex partial (psychomotor) seizuresFDA-labeled
Prevention and treatment of seizures occurring during or after neurosurgeryFDA-labeled
IV: treatment of generalized convulsive status epilepticusFDA-labeled
IV: short-term substitution for oral phenytoin when oral administration is not feasibleFDA-labeled

Class IB antiarrhythmic for certain ventricular arrhythmias (including digoxin toxicity–related arrhythmias)Off-label
Trigeminal neuralgia (second-line)Off-label

Blocks voltage-gated sodium channels in a use- and voltage-dependent manner, stabilizing neuronal membranes and limiting the spread of seizure activity
Also modulates calcium conductance and reduces post-tetanic potentiation at synapses

Oral loading: 15–20mg/kg in divided doses when rapid effect is needed; usual adult maintenance ~300–400mg/day, dosing frequency depends on formulation (extended vs. prompt-release)
Typical maintenance ~100mg PO/IV every 6–8 hours, individualized to serum levels
Exhibits nonlinear (zero-order/saturable) kinetics near therapeutic concentrations — small dose increases can cause disproportionately large rises in serum level; increase doses cautiously in small increments once near the therapeutic range
Total therapeutic serum range is conventionally cited as ~10–20mcg/mL; free (unbound) phenytoin ~1–2mcg/mL
IV infusion should be given into a large vein through a patent catheter, diluted only in normal saline with an in-line filter, to reduce precipitation and purple glove syndrome risk
Intramuscular administration should generally be avoided due to erratic absorption and local tissue injury

Dose interpretation and adjustment required in hepatic impairment or hypoalbuminemia — use corrected or free phenytoin levels

IV loading for status epilepticus: 10–20mg/kg at a rate not exceeding 50mg/min in adults (1–3mg/kg/min in pediatric patients), with continuous ECG/BP monitoring

Hypersensitivity to phenytoin or other hydantoins
Sinus bradycardia, sinoatrial block, second- or third-degree AV block, or Adams-Stokes syndrome
Prior history of acute hepatotoxicity attributed to phenytoin
Concurrent use with delavirdine (risk of loss of virologic response and resistance)

Substrate of CYP2C9/CYP2C19 with a narrow therapeutic index — inhibitors (fluconazole, isoniazid, cimetidine, amiodarone) can substantially raise levels
Strong inducer of CYP3A4 and other hepatic enzymes — reduces efficacy of warfarin, hormonal contraceptives, corticosteroids, and many antiretrovirals
Highly protein-bound (~90%) — displacement interactions with valproate and other highly protein-bound drugs can alter the free fraction
Contraindicated with delavirdine
Enteral tube feeds can reduce phenytoin absorption; separate dosing from feeds when possible

Dose-related CNS toxicity: nystagmus, ataxia, slurred speech, diplopia, cognitive slowing, sedation
Gingival hyperplasia with long-term use — reinforce dental hygiene and regular dental care
Hirsutism, coarsening of facial features, and acne with chronic therapy
Purple glove syndrome — edema, discoloration, and pain distal to the IV site, potentially progressing to skin necrosis or limb ischemia
Cardiac arrhythmias and severe hypotension with rapid IV administration
Rare but serious: Stevens-Johnson syndrome/TEN, DRESS, hepatotoxicity, blood dyscrasias
Osteopenia/osteomalacia and peripheral neuropathy with long-term therapy

Serum phenytoin concentration (total goal ~10–20mcg/mL; free level in hypoalbuminemia or renal disease)
Serum albumin to help interpret total vs. free phenytoin levels
CBC and liver function periodically with chronic use
Continuous ECG and blood pressure monitoring during IV administration
Periodic dental/gingival examination
Bone density with long-term therapy

Associated with fetal hydantoin syndrome (craniofacial anomalies, nail/digit hypoplasia, growth and cognitive impairment)
Maternal vitamin K supplementation late in pregnancy and neonatal vitamin K administration are used to reduce neonatal hemorrhagic risk
Present in breast milk in small amounts; generally considered compatible with breastfeeding with monitoring of the infant