, Pfizer Holding France
) is a water-soluble phenytoin prodrug
used only in hospitals for the treatment of epileptic seizures
On 18 November 2004, Sicor (a subsidiary of Teva) received a tentative approval letter from the United States Food and Drug Administration for a generic version of fosphenytoin.
Fosphenytoin is approved in the United States for the short term (five days or less) 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; vomiting, and/or the patient is unalert or not awake or both.
In April 2003, Applebaum and colleagues at the Ben-Gurion University of the Negev
reported that even though anticonvulsants
are often very effective in mania
, and acute mania requires rapid treatment, fosphenytoin had no antimanic effect even 60 minutes after administration of doses used in status epilepticus.
Fosphenytoin was more successfully used to relieve pain refractory to opiates in a 37-year-old woman with neuroma, according to Dr. Gary J. McCleane of the Rampark Pain Center in Lurgan, Northern Ireland. She was given 1,500 phenytoin equivalent units of fosphenytoin over a 24 hour period, producing pain relief that last three to fourteen weeks after each infusion, allowing her to use less opiates.
One mmol (millimole
) of phenytoin is produced for every mmol of fosphenytoin administered; the hydrolysis
of fosphenytoin also yields phosphate
, the latter of which is subsequently metabolized to formate
, which is in turn metabolized by a folate dependent mechanism.
Side effects are similar to phenytoin, except that fosphenytoin causes less hypotension
and more paresthesia
. Fosphenytoin can cause hyperphosphatemia
in end-stage renal failure
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 soluble
in water. Simply putting patients on other drugs is not always an option; this was especially true before 1993, when the number of anticonvulsants
available was much more limited. One solution was to develop a prodrug that did not have these drawbacks.
Fosphenytoin was approved by the Food and Drug Administration (FDA) on August 5, 1996 for use in epilepsy.
Notes and references