II. Classification: Hydantoin
- Phenytoin (Dilantin)
- Fosphenytoin (Cerebyx)
- Phenytoin congeners (limited use)
- Mephenytoin
- Ethotoin
- Phenacemide
III. History
- Phenytoin is the oldest non-Sedative antiepileptic drug (1938)
- Developed based on research into Phenobarbital antiseizure effect
IV. Indications
- Partial Seizures
- Generalized tonic-clonic Seizures
V. Contraindications
- Pregnancy (See Fetal Hydantoin Syndrome)
VI. Pharmacokinetics: Phenytoin
- Fosphenytoin (Cerebyx) has similar Pharmacokinetics to Phenytoin
- 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
VII. Dosing: Phenytoin or Dilantin (Adults)
-
Status Epilepticus
- Dose: 20 mg/kg IV (at 1 mg/kg/min up to 50 mg/min) up to to 1000 mg maximum
- May repeat once with Phenytoin 5-10 mg/kg IV
- Maintenance with Phenytoin 50 mg/min
- Loading dose
- Oral loading regimen
- Dose 1: 400 mg orally
- Dose 2: 300-400 mg orally at 2 hours after dose 1
- Dose 3: 300-400 mg orally at 4 hours after dose 1
- Parenteral loading regimen
- Dose: 10-20 mg/kg (average 1 gram) IV
- Do not administer faster than 50 mg/min
- Oral loading regimen
- Maintenance dose
- Initial: 5 mg/kg to 300 mg/day divided qd to tid
- Titrating dose
- Avoid increasing dose by >25-30 mg per trial
- Wait for steady state (7 days) before level recheck
VIII. Dosing: Fosphenytoin or Cerebyx
-
Status Epilepticus
- Dose: 20 mg/kg IV or IM (at 3 mg/kg/min up to 150 mg/min) up to 1000 mg maximum
- Preferred over Phenytoin for Status Epilepticus
- Fosphenytoin can be infused with dextrose
- Fosphenytoin has lower risk of Arrhythmia (due to no Ethylene Glycol in base)
- Fosphenytoin may be given IM or delivered a faster IV rate (not tissue toxic)
- However onset of activity is similar to that with Phenytoin (as Fosphenytoin is converted to active Phenytoin form)
IX. Drug Interactions
- Drugs that increase plasma Phenytoin levels
- Amiodarone
- Clobazam
- Fluconazole
- Ranitidine
- Phenylbutazone
- Sulfonamides
- Benzodiazepines
- Anticoagulants
- Isoniazid
- Drugs that decrease Phenytoin level or free fraction
- Influenza Vaccine
- Tolbutamide
- Carboplatin
- Rifampicin
- Theophylline
- Phenobarbital
- Carbamazepine
- Phenytoin decreases plasma level of other drug
- Doxorubicin
X. Adverse Effects
- See Dilantin Toxicity
- Fetal Hydantoin Syndrome
- Drug Hypersensitivity
- Common chronic changes associated with Phenytoin
- Gingival Hyperplasia
- Hirsutism
- Coarse facial features
- Peripheral Neuropathy (decreased Deep Tendon Reflex)
- Other effects
- Hepatotoxicity
- Stevens-Johnson Syndrome
- Pancreatitis
- Osteoporosis
- Folic Acid Deficiency
- Drug-Induced Rash
XI. Monitoring
- Routine Labs every 6 to 12 months
- Complete Blood Count with Platelet Count (myelosuppression risk)
- Liver Function Tests (hepatotoxicity risk)
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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 |