II. Classification: Hydantoin
- Phenytoin (Dilantin)
- Fosphenytoin (Cerebyx)
- Phenytoin congeners (limited use)
- Mephenytoin
- Ethotoin
- Phenacemide
III. Mechanism
IV. History
- Phenytoin is the oldest non-Sedative antiepileptic drug (1938)
- Developed based on research into Phenobarbital antiseizure effect
V. Indications
- Partial Seizures
- Generalized tonic-clonic Seizures
VI. Contraindications
- Pregnancy (See Fetal Hydantoin Syndrome)
VII. Pharmacokinetics: Phenytoin
- Fosphenytoin (Cerebyx) has similar Pharmacokinetics to Phenytoin and is preferred for IV use
- Hepatic metabolism
- Highly Protein bound
- Phenytoin levels must be interpreted with Serum Albumin level in mind
- Onset: 10-30 minutes
-
Half-Life: 12 to 24-36 hours
- Average half life for moderate dosages: 24 hours
- Very long Half-Life at toxic concentrations
- Therapeutic level: 10-20 mcg/ml
VIII. Dosing: Phenytoin or Dilantin (Adults)
-
Status Epilepticus
- Fosphenytoin is preferred for IV use
- Initial: 20 mg/kg IV (at 1 mg/kg/min up to 50 mg/min) up to to 1000 mg maximum
- May repeat once at 5-10 mg/kg IV
- Maintenance: 50 mg/min or 100 mg IV or orally every 6 to hours
-
Epilepsy
- Start Option 1: Oral dose start
- Start 100 mg orally three times daily
- Advance dosing based on serum concentrations
- Start Option 2: Oral loading regimen
- Dose 1: 400 mg orally
- Dose 2: 300 mg orally at 2 hours after dose 1
- Dose 3: 300 mg mg orally at 4 hours after dose 1
- Start subsequent maintenance dosing on next day
- Start Option 3: Parenteral loading regimen
- Dose: 10-20 mg/kg (average 1 gram) IV
- Do not administer faster than 50 mg/min
- Maintenance dose
- Initial: 5 mg/kg to 300 mg/day divided daily to three times daily
- Titrating dose
- Avoid increasing dose by >25-30 mg per trial
- Wait for steady state (7 days) before level recheck
- Start Option 1: Oral dose start
IX. Dosing: Phenytoin or Dilantin (Children)
-
Status Epilepticus
- Fosphenytoin is preferred for IV use
- Initial: 15 to 20 mg/kg IV (at 1 mg/kg/min up to 50 mg/min)
- May repeat once at 5-10 mg/kg IV
-
Epilepsy
- Start 5 mg/kg/day orally divided 2 to 3 times daily
- Titrate to therapeutic serum level
- Typical range: 4 to 8 mg/kg/day up to 300 mg/day
X. Drug Interactions
- Decreases Oral Contraceptive efficacy
- Drugs that increase plasma Phenytoin levels
- Drugs that decrease Phenytoin level or free fraction
- Influenza Vaccine
- Tolbutamide
- Carboplatin
- Rifampicin
- Theophylline
- Phenobarbital
- Carbamazepine
- Phenytoin decreases plasma level of other drug
- Doxorubicin
XI. Adverse Effects
- See Dilantin Toxicity
- Fetal Hydantoin Syndrome
- Neurologic effects
- Intravenous Effects
- CNS Depression
- Severe Hypotension
- Arrhythmias
-
Drug Hypersensitivity
- Fever
- Lymphadenopathy
- Drug-Induced Agranulocytosis or Bone Marrow suppression
- Common chronic changes associated with Phenytoin
- Gingival Hyperplasia
- Hirsutism
- Coarse facial features
- Peripheral Neuropathy (decreased Deep Tendon Reflex)
- Other effects
- Hepatotoxicity
- Drug-Induced Rash
- Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis
- More common in Asian heritage with HLA-B 1502 Mutation
- Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS Syndrome)
- Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis
- Pancreatitis
- Osteoporosis
- Folic Acid Deficiency
XII. Monitoring
- Monitor Phenytoin levels to ensure in therapeuti range
- Hypoalbuminemia may increase free fraction of Phenytoin
- Routine Labs every 6 to 12 months
- Complete Blood Count with Platelet Count (myelosuppression risk)
- Liver Function Tests (hepatotoxicity risk)
- May decrease circulating Thyroid Hormone
- May increase Thyroid Stimulating Hornone (TSH)
XIII. Safety
- Pregnancy: Category D
- Lactation: Contraindicated
XIV. Resources
- Phenytoin Injection (DailyMed)
- Phenytoin Extended Release Capsule (DailyMed)
- Phenytoin Capsule (DailyMed)
XV. References
- (2022) Presc Lett, Resource #361206, Antiseizure Medications
- Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 56-7
- Hamilton (2020) Tarascon Pocket Pharmacopoeia
Images: Related links to external sites (from Bing)
Related Studies
| phenytoin (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| PHENYTOIN 125 MG/5 ML SUSP | Generic | $0.08 per ml |
| PHENYTOIN 50 MG INFATAB CHEW | Generic | $0.23 each |
| PHENYTOIN 50 MG TABLET CHEW | Generic | $0.23 each |
| PHENYTOIN SOD EXT 100 MG CAP | Generic | $0.13 each |
| PHENYTOIN SOD EXT 200 MG CAP | Generic | $1.00 each |
| PHENYTOIN SOD EXT 300 MG CAP | Generic | $1.72 each |
| dilantin (on 3/23/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| DILANTIN 100 MG CAPSULE | Generic | $0.13 each |
| DILANTIN 30 MG CAPSULE | $1.23 each | |
| DILANTIN 50 MG INFATAB | Generic | $0.23 each |