BLACK BOX WARNING
- IV administration: hypotension and cardiac arrhythmias require cardiac monitoring
phenytoin
Brand: Dilantin, Phenytek
⚠ BBW Beers Criteria TDM Required Prototype Drug
Drug Class: antiepileptic
Drug Family: antiepileptic
Subclass: hydantoin
Organ Systems: cns
Mechanism of Action
Blocks voltage-gated sodium channels in their inactivated state, stabilizing neuronal membranes and reducing repetitive firing.
voltage-gated sodium channels
Indications
- tonic-clonic seizures
- focal seizures
- status epilepticus (IV)
- cardiac arrhythmias (IV)
Contraindications
- sinus bradycardia
- SA block
- second/third-degree AV block
- Adams-Stokes syndrome
- concurrent delavirdine use
Adverse Effects
Common
- nystagmus
- ataxia
- diplopia
- gingival hyperplasia
- hirsutism
- coarsening of facial features
Serious
- Stevens-Johnson syndrome
- toxic epidermal necrolysis
- hepatotoxicity
- blood dyscrasias
- purple glove syndrome (IV)
Pharmacokinetics (ADME)
| Absorption | Oral bioavailability ~90%; highly variable due to saturable (zero-order) kinetics |
| Distribution | Highly protein-bound (~90% albumin); Vd 0.6–0.8 L/kg; crosses BBB |
| Metabolism | Hepatic via CYP2C9 and CYP2C19; saturable kinetics — small dose increases cause large level increases |
| Excretion | Renal as hydroxylated metabolites; <5% unchanged |
| Half-life | 7–42 hours (dose-dependent) |
| Onset | IV: minutes; oral: 2–4 hours |
| Peak | 4–12 hours (oral extended release) |
| Duration | 24 hours |
| Protein Binding | ~90% |
| Vd | 0.6–0.8 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| warfarin | CYP2C9 induction reduces warfarin levels | major |
| valproate | displaces phenytoin from protein binding; complex interaction | major |
| oral contraceptives | CYP induction reduces contraceptive efficacy | major |
Nursing Considerations
- Monitor free and total phenytoin levels; therapeutic range 10–20 mcg/mL (total) or 1–2 mcg/mL (free); check free levels in hypoalbuminemia
- IV phenytoin: administer no faster than 50 mg/min in adults; monitor ECG and BP continuously; use normal saline only (precipitates in dextrose)
- Monitor for signs of toxicity: nystagmus at 20 mcg/mL, ataxia at 30 mcg/mL, lethargy at >40 mcg/mL
- Educate patient about gingival hygiene, avoid abrupt discontinuation, and the extensive drug interaction profile
Clinical Pearls
- Phenytoin exhibits zero-order (saturable) kinetics at therapeutic levels — small dose increases can cause disproportionately large rises in serum concentration
- Fosphenytoin is a prodrug preferred IV/IM because it avoids the propylene glycol toxicity and injection site reactions of phenytoin
Safety Profile
Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.