Fosphenytoin and phenytoin in patients with status epilepticus: improved tolerability versus increased costs

Drug Saf. 2000 Jun;22(6):459-66. doi: 10.2165/00002018-200022060-00004.


Tonic-clonic status epilepticus (TCSE) is the most common neurological emergency and affects approximately 60000 patients each year in the US. The risk of complications increases substantially as TCSE lasts longer than 60 minutes. Ideally, drugs used to treat this condition should be well tolerated when administered as rapid intravenous infusions and should not interfere with patients' state of consciousness or cardiovascular and respiratory functions. Because of its efficacy, absence of sedation or respiratory suppression, intravenous phenytoin has largely replaced phenobarbital (phenobarbitone) as the second agent of choice (following the administration of a benzodiazepine) in the treatment of TCSE. While the efficacy of phenytoin in the treatment of acute seizures and TCSE is well established, the parenteral formulation of phenytoin has several inherent shortcomings which compromise its tolerability and limit the rate of administration. Intravenous phenytoin has been associated with fatal haemodynamic complications and serious reactions at the injection site including skin necrosis and amputation of extremities. Fosphenytoin, a phenytoin prodrug, has the same pharmacological properties as phenytoin but none of the injection site and cardiac rhythm complications of intravenous infusions of phenytoin. While fosphenytoin costs more than intravenous phenytoin, treating the acute and chronic complications of TCSE itself, and the complications of intravenous phenytoin can also be costly. All other factors being equal, there is no doubt that fosphenytoin is better tolerated and can be delivered faster than intravenous phenytoin; 2 measures that clearly improve outcome in patients with TCSE. The tolerability of intramuscular fosphenytoin also extends its use to clinical situations where prompt administration of a nondepressing anticonvulsant is indicated but secure intravenous access and cardiac monitoring are not available, such as treatment of seizures by rescue squads in the field and serial seizures in the institutionalised, elderly and other patients with intractable epilepsy.

Publication types

  • Review

MeSH terms

  • Anticonvulsants / adverse effects*
  • Anticonvulsants / economics
  • Anticonvulsants / therapeutic use*
  • Humans
  • Phenytoin / adverse effects*
  • Phenytoin / analogs & derivatives*
  • Phenytoin / economics
  • Phenytoin / therapeutic use*
  • Status Epilepticus / drug therapy*
  • Status Epilepticus / economics


  • Anticonvulsants
  • Phenytoin
  • fosphenytoin