II. Classification: Hydantoin

  1. Phenytoin (Dilantin)
  2. Fosphenytoin (Cerebyx)
  3. Phenytoin congeners (limited use)
    1. Mephenytoin
    2. Ethotoin
    3. Phenacemide

III. History

  1. Phenytoin is the oldest non-Sedative antiepileptic drug (1938)
  2. Developed based on research into Phenobarbital antiseizure effect

IV. Indications

  1. Partial Seizures
  2. Generalized tonic-clonic Seizures

V. Contraindications

  1. Pregnancy (See Fetal Hydantoin Syndrome)

VI. Pharmacokinetics: Phenytoin

  1. Fosphenytoin (Cerebyx) has similar Pharmacokinetics to Phenytoin
  2. Hepatic metabolism
  3. Highly Protein bound
    1. Phenytoin levels must be interpreted with Serum Albumin level in mind
  4. Onset: 10-30 minutes
  5. Half-Life: 12 to 24-36 hours
    1. Average half life for moderate dosages: 24 hours
    2. Very long Half-Life at toxic concentrations
  6. Therapeutic level: 10-20 mcg/ml

VII. Dosing: Phenytoin or Dilantin (Adults)

  1. Status Epilepticus
    1. Dose: 20 mg/kg IV (at 1 mg/kg/min up to 50 mg/min) up to to 1000 mg maximum
    2. May repeat once with Phenytoin 5-10 mg/kg IV
    3. Maintenance with Phenytoin 50 mg/min
  2. Loading dose
    1. Oral loading regimen
      1. Dose 1: 400 mg orally
      2. Dose 2: 300-400 mg orally at 2 hours after dose 1
      3. Dose 3: 300-400 mg orally at 4 hours after dose 1
    2. Parenteral loading regimen
      1. Dose: 10-20 mg/kg (average 1 gram) IV
      2. Do not administer faster than 50 mg/min
  3. Maintenance dose
    1. Initial: 5 mg/kg to 300 mg/day divided qd to tid
  4. Titrating dose
    1. Avoid increasing dose by >25-30 mg per trial
    2. Wait for steady state (7 days) before level recheck

VIII. Dosing: Fosphenytoin or Cerebyx

  1. Status Epilepticus
    1. Dose: 20 mg/kg IV or IM (at 3 mg/kg/min up to 150 mg/min) up to 1000 mg maximum
  2. Preferred over Phenytoin for Status Epilepticus
    1. Fosphenytoin can be infused with dextrose
    2. Fosphenytoin has lower risk of Arrhythmia (due to no Ethylene Glycol in base)
    3. Fosphenytoin may be given IM or delivered a faster IV rate (not tissue toxic)
      1. However onset of activity is similar to that with Phenytoin (as Fosphenytoin is converted to active Phenytoin form)

IX. Drug Interactions

  1. Drugs that increase plasma Phenytoin levels
    1. Amiodarone
    2. Clobazam
    3. Fluconazole
    4. Ranitidine
    5. Phenylbutazone
    6. Sulfonamides
    7. Benzodiazepines
    8. Anticoagulants
    9. Isoniazid
  2. Drugs that decrease Phenytoin level or free fraction
    1. Influenza Vaccine
    2. Tolbutamide
    3. Carboplatin
    4. Rifampicin
    5. Theophylline
    6. Phenobarbital
    7. Carbamazepine
  3. Phenytoin decreases plasma level of other drug
    1. Doxorubicin

XI. Monitoring

  1. Routine Labs every 6 to 12 months
    1. Complete Blood Count with Platelet Count (myelosuppression risk)
    2. Liver Function Tests (hepatotoxicity risk)

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Related Studies

Cost: Medications

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