Fosphenytoin

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General

Adult Dosing

  • Generalized Convulsive Status Epilepticus
    • 15-20mg/kg IV, infuse at 100-150mg/min
  • Nonemergent Seizure
    • Load: 10-20mg/kg IV/IM
    • Initial Maintenance: 4-6mg/kg/day IV/IM
  • Short-Term Substitution for PO Phenytoin
    • Can be substituted for PO phenytoin therapy at the same total daily dose
  • Administration
    • Maximum IV rate of 150mg PE/min
  • Monitor: phenytoin level 2 hr after IV, 4 hr after IM
  • All dosing in mg "phenytoin equivalents" (PE); 75mg fosphenytoin equivalent to 50mg phenytoin

Pediatric Dosing

  • Safety and efficacy not established

Special Populations

  • Pregnancy Rating: D
  • Lactation: excretion in milk unknown, not recommended
  • Renal Dosing: not defined, caution advised
  • Hepatic Dosing: not defined, caution advised

Contraindications

  • Allergy to class/drug
  • Sinus bradycardia, sinoatrial block, 2nd or 3rd degree AV block, Adams-Stokes syndrome
  • Not indicated for absence seizures or seizures secondary to hypoglycemia or other metabolic disorder
  • Coadministration with delavirdine; potential for loss of virologic response and possible resistance to delavirdine or to the pharmacologic class of NNRTIs

Adverse Reactions

Serious

  • Black Box Warnings
    • Cardiovascular risk associated with rapid infusion rates
    • Risk of hypotension and arrhythmias with infusion rates that exceed 150mg/minute of phenytoin sodium equivalents (PE)
    • Careful cardiac monitoring is needed during and after administering IV administration
    • These events have also been reported at or below 150mg/minute
    • Reduce infusion rate or discontinuation may be needed
  • Cardiovascular collapse
  • Toxic delirium
  • Bradycardia
  • Arrhythmias
  • Exfoliative dermatitis
  • Stevens-Johnson
  • Toxic epidermal necrolysis
  • Drug rash with eosinophilia and systemic sx
  • Hepatotoxicity
  • Thrombocytopenia
  • Leukopenia
  • Agranulocytosis
  • Pancytopenia
  • Anemia
  • Purple glove syndrome (IV use)

Common

  • Nystagmus
  • Dizziness
  • Pruritis
  • Paresthesia
  • Headache
  • Somnolence
  • Ataxia
  • Nausea
  • Tinnitus
  • Rash
  • Tremor
  • Hypotension
  • Xerostomia
  • Confusion
  • Blurred vision
  • Taste changes
  • Fever
  • Injection site reaction
  • Constipation
  • Hypokalemia

Pharmacology

  • Half-life: 15 min (phenytoin)
  • Metabolism: CYP450; prodrug metabolized to phenytoin
  • Excretion: urine
  • Mechanism of Action: modulates neuronal voltage-dependent Na and Ca channels

See Also

References

epocrates, medscape