Absorption: Absorbed slowly from the GI tract. Bioavailability differs among products; the Dilantin and Phenytek preparations are considered to be "extended" products. Other products are considered to be prompt release.
Distribution: Distributes into CSF and other body tissues and fluids. Enters breast milk; crosses the placenta, achieving similar maternal/fetal levels. Preferentially distributes into fatty tissue.
Protein Binding: Adults 90–95%; ↓ protein binding in neonates (up to 20% free fraction available), infants (up to 15% free), and patients with hyperbilirubinemia, hypoalbuminemia, severe renal dysfunction or uremia.
Metabolism/Excretion: Mostly metabolized by the liver via the CYP2C9 isoenzyme, and to a lesser extent by the CYP2C19 isoenzyme; the CYP2C9 isoenzyme exhibits genetic polymorphism (intermediate or poor metabolizers may have significantly ↑ phenytoin concentrations and an ↑ risk of adverse reactions).; minimal amounts excreted in the urine.
Half-life: 22 hr (range 7–42 hr).
Contraindicated in:
- Hypersensitivity
- Hypersensitivity to propylene glycol (phenytoin injection only)
- History of hepatotoxicity related to phenytoin
- Alcohol intolerance (phenytoin injection and liquid only)
- Sinus bradycardia, sinoatrial block, 2nd- or 3rd-degree heart block, or Stokes-Adams syndrome (phenytoin injection only)
- OB: Pregnancy (may cause fetal harm) (↑ risk of congenital anomalies; ↑ risk of hemorrhage in newborn if used at term).
Use Cautiously in:
- All patients (may ↑ risk of suicidal thoughts/behaviors)
- Hepatic or renal disease (↑ risk of adverse reactions; dose reduction recommended for hepatic impairment)
- Severe cardiac or respiratory disease (use of IV phenytoin may result in an ↑ risk of serious adverse reactions)
- Cardiac disease (↑ risk of cardiac arrest or bradycardia)
- CYP2C9 intermediate or poor metabolizers (↑ risk of phenytoin toxicity)
- Lactation: Use while breastfeeding only if potential maternal benefit justifies potential harm to infant
- Pedi: Suspension contains sodium benzoate, a metabolite of benzyl alcohol that can cause potentially fatal gasping syndrome in neonates
- Geri: Use of IV phenytoin may result in an ↑ risk of serious adverse reactions in older adults.
Exercise Extreme Caution in:
- Patients positive for HLA-B*1502 allele or carriers of CYP2C9*3 variant (unless benefits clearly outweigh the risks) (↑ risk of serious skin reactions).
Most listed are for chronic use of phenytoin
CV: CARDIAC ARREST, hypotension (↑ with IV phenytoin), bradycardia, tachycardia.
Derm: ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, hypertrichosis, rash, exfoliative dermatitis, pruritus, purple glove syndrome.
EENT: diplopia, nystagmus.
GI: ACUTE HEPATIC FAILURE, gingival hyperplasia, nausea, constipation, drug-induced hepatitis, vomiting.
Hemat: AGRANULOCYTOSIS, APLASTIC ANEMIA, leukopenia, megaloblastic anemia, thrombocytopenia.
MS: osteomalacia, osteoporosis.
Neuro: SUICIDAL THOUGHTS, ataxia, agitation, confusion, dizziness, drowsiness, dysarthria, dyskinesia, extrapyramidal syndrome, headache, insomnia, vertigo, weakness.
Misc: ANGIOEDEMA, fever, lymphadenopathy.
IM administration is not recommended due to erratic absorption and pain on injection. Oral route should be used whenever possible.
Anticonvulsant
- PO (Adults): Loading dose of 15–20 mg/kg as extended capsules in 3 divided doses given every 2–4 hr; maintenance dose 5–6 mg/kg/day given in 1–3 divided doses; usual dosing range = 200–1200 mg/day.
- PO (Children 10–16 yr): 6–7 mg/kg/day in 2–3 divided doses.
- PO (Children 7–9 yr): 7–8 mg/kg/day in 2–3 divided doses.
- PO (Children 4–6 yr): 7.5–9 mg/kg/day in 2–3 divided doses.
- PO (Children 0.5–3 yr): 8–10 mg/kg/day in 2–3 divided doses.
- PO (Neonates up to 6 mo): 5–8 mg/kg/day in 2 divided doses, may require every 8 hr dosing.
- IV (Adults): Status epilepticus loading dose — 15–20 mg/kg. Rate not to exceed 25–50 mg/min. Maintenance dose — same as PO dosing above.
- IV (Children): Status epilepticus loading dose — 15–20 mg/kg at 1–3 mg/kg/min. Maintenance dose — same as PO dosing above.
Antiarrhythmic
- IV (Adults): 50–100 mg every 10–15 min until arrhythmia is abolished, or a total of 15 mg/kg has been given, or toxicity occurs.
- PO (Adults): Loading dose: 250 mg 4 times daily for 1 day, then 250 mg twice daily for 2 days, then maintenance at 300–400 mg/day in divided doses 1–4 times/day.
- IV (Children): 1.25 mg/kg every 5 min, may repeat up to total loading dose of 15 mg/kg. Maintenance dose — 5–10 mg/kg/day in 2–3 divided doses IV or PO.
Therapeutic Classification: antiarrhythmics (group IB), anticonvulsants
Pharmacologic Classification: hydantoins
(anticonvulsant effect)
* = time required for onset of action without a loading dose.
