Phenytoin

DILANTIN

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What it isSodium-channel blocker; focal and tonic-clonic seizures, and status epilepticus.

Why it mattersSaturable metabolism makes serum levels rise disproportionately, while strong enzyme induction reshapes the rest of the regimen.

What it changesCheck free levels when albumin is low; nystagmus, ataxia and confusion mark toxicity. Gingival overgrowth and severe rash limit long use.

FDA-approved for

seizures (~1953)

Off-label

status epilepticus
trigeminal neuralgia

FDA label

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FDA dosing	Population	Start	Target	Max
Seizures (previously untreated)	Adult	100 mg TID	100 mg TID-QID	200 mg TID
Seizures, once-daily maintenance	Adult (controlled on 300 mg/day divided)	300 mg QD
Seizures	Pediatric	5 mg/kg/day divided BID-TID	4-8 mg/kg/day	300 mg/day

Renal Monitor unbound (free) phenytoin concentrations

Hepatic Monitor unbound (free) phenytoin concentrations

Once-daily 300 mg only for patients controlled on 300 mg/day; extended and prompt forms are not interchangeable.

Instructions

Do not discontinue abruptly (risk of status epilepticus); taper gradually
Discontinue at first sign of rash (SJS/TEN risk)
Monitor serum levels; therapeutic total 10-20 mcg/mL (unbound 1-2 mcg/mL)
Loading dose reserved for clinic/hospital settings

Contraindications

Prior acute hepatotoxicity attributable to phenytoin
Coadministration with delavirdine

Cautions

Withdrawal-precipitated seizures/status epilepticus — taper gradually
Serious dermatologic reactions (SJS/TEN); DRESS/multiorgan hypersensitivity
Suicidal behavior/ideation
Cardiac: bradycardia and cardiac arrest reported
Angioedema; hepatic injury; hematopoietic complications
Effects on vitamin D/bone; exacerbation of porphyria

Adverse reactions

Most common (dose-related CNS): nystagmus, ataxia, slurred speech, decreased coordination, somnolence, mental confusion
Dizziness, vertigo, insomnia, transient nervousness, motor twitchings, paresthesias, headache
Gingival hyperplasia, nausea, vomiting, constipation, enlargement of the lips
Rash (morbilliform most common); serious/fatal forms: SJS/TEN, acute generalized exanthematous pustulosis, bullous/exfoliative/purpuric dermatitis; DRESS; anaphylaxis; angioedema; hypertrichosis; urticaria
Hematologic: thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, pancytopenia (some fatal); macrocytosis/megaloblastic anemia (folate-responsive); lymphadenopathy/pseudolymphoma; pure red cell aplasia
Hepatic: acute hepatic failure, toxic hepatitis, liver damage
Coarsening of facial features, systemic lupus erythematosus, periarteritis nodosa, immunoglobulin abnormalities
Long-term: sensory peripheral polyneuropathy, dyskinesias (chorea, dystonia, tremor, asterixis), cerebellar atrophy
Labs: decreased T4/T3 (± increased TSH), increased glucose, alkaline phosphatase, GGT
Altered/metallic taste; Peyronie's disease

Pregnancy Increases risk of congenital malformations (orofacial clefts, cardiac defects) and fetal hydantoin syndrome; enroll in NAAED registry.

Lactation Phenytoin is secreted in human milk; weigh benefits against risk to breastfed infant.

NO BOXED WARNINGS

Principal riskNonlinear kinetics: a small dose rise can cause toxicity

Cost, est. cash$10–$500/month

Generic entry1984