Fosphenytoin, also known as fosphenytoin sodium, and sold under the brand name Cerebyx among others, is a water-soluble phenytoin prodrug that is administered intravenously to deliver phenytoin, potentially more safely than intravenous phenytoin. It is used in the acute treatment of convulsive status epilepticus.
Fosphenytoin was developed in 1996.
Medical uses
Fosphenytoin is approved in the United States for the short-term (five days or fewer) treatment of epilepsy when more widely used means of phenytoin administration are not possible or are ill-advised,
such as endotracheal intubation, status epilepticus or some other type of repeated seizures; cluster seizure, vomiting, and/or the patient is unalert or not awake or both.
Other
In 2003, it was reported that even though
are often very effective in
mania, and acute mania requires rapid treatment, fosphenytoin had no antimanic effect.
Metabolism
One
of phenytoin is produced for every millimole of fosphenytoin administered; the
hydrolysis of fosphenytoin also yields
phosphate and
formaldehyde, the latter of which is subsequently metabolized to
formate, which is in turn metabolized by a folate dependent mechanism.
Side effects
Side effects are similar to intravenous phenytoin and include hypotension, cardiac
arrhythmias, CNS adverse events (
nystagmus, dizziness, sedation/somnolence,
ataxia and
stupor), and local dermatological reactions. Purple glove syndrome probably occurs with fosphenytoin but possibly at lower frequency than with intravenous phenytoin. Fosphenytoin can cause hyperphosphatemia in end-stage
renal failure patients.
History
Phenytoin, in both its acidic and sodium salt forms, is erratically bioavailable whether it is injected or taken orally due to its high
melting point, weak
acidity, and its being only sparingly
solubility in water.
Simply putting patients on other drugs is not always an option; this was especially true before 1993, when the number of
available was much more limited.
[ ] One solution was to develop a prodrug that did not have these drawbacks.
Fosphenytoin was approved by the US Food and Drug Administration (FDA) in August 1996, for use in epilepsy.
