Phenytoin

Aka: Phenytoin, Dilantin, Fosphenytoin, Cerebyx, Diphenylhydantoin, DPH, Hydantoin, Mephenytoin, Ethotoin, Phenacemide

1. Classification: Hydantoin
   1. Phenytoin (Dilantin)
   2. Fosphenytoin (Cerebyx)
   3. Phenytoin congeners (limited use)
      1. Mephenytoin
      2. Ethotoin
      3. Phenacemide
2. History
   1. Phenytoin Oldest non-sedative antiepileptic drug (1938)
   2. Based on research into phenobarbital antiseizure effect
3. Indications
   1. Partial Seizures
   2. Generalized tonic-clonic Seizures
4. Contraindications
   1. Pregnancy (See Fetal Hydantoin Syndrome)
5. Pharmacokinetics: Phenytoin
   1. Fosphenytoin (Cerebyx) has similar pharmacokinetics to Phenytoin
   2. Hepatic metabolism
   3. Highly protein bound
   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
6. 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
7. 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)
8. 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
9. Adverse Effects
   1. See Dilantin Toxicity
   2. Fetal Hydantoin Syndrome
   3. Drug hypersensitivity
      1. Fever
      2. Lymphadenopathy
      3. Drug-Induced Agranulocytosis
   4. Common chronic changes associated with Phenytoin
      1. Gingival Hyperplasia
      2. Hirsutism
      3. Coarse facial features
      4. Peripheral Neuropathy (decreased Deep Tendon Reflex)
   5. Other effects
      1. Hepatotoxicity
      2. Stevens-Johnson Syndrome
      3. Pancreatitis
      4. Osteoporosis
      5. Folic Acid Deficiency