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PhenytoinAka: Dilantin, Diphenylhydantoin, DPH, Hydantoin, Mephenytoin, Ethotoin, Phenacemide

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  1. Classification: Hydantoin
    1. Phenytoin (Dilantin)
    2. Phenytoin congeners (limited use)
      1. Mephenytoin
      2. Ethotoin
      3. Phenacemide
  2. History
    1. 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
    1. Hepatic metabolism
    2. Highly protein bound
    3. Half-life: 12 to 36 hours
      1. Average half life for moderate dosages: 24 hours
      2. Very long half-life at toxic concentrations
    4. Therapeutic level: 10-20 ug/ml
  6. Dosing: Adults
    1. Loading dose
      1. Oral loading regimen
        1. Dose 1: 400 mg PO
        2. Dose 2: 300 mg PO at 2 hours after dose 1
        3. Dose 3: 300 mg PO 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
    2. Maintenance dose
      1. Initial: 5 mg/kg to 300 mg/day divided qd to tid
    3. Titrating dose
      1. Avoid increasing dose by >25-30 mg per trial
      2. Wait for steady state (7 days) before level recheck
  7. 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
  8. 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

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