Fosphenytoin

Fosphenytoin

File:Fosphenytoin.svg
File:Fosphenytoin3d.png
Clinical data
Pregnancy category	US: D (Evidence of risk)
Routes of administration	Intravenous, intramuscular
ATC code	N03AB05 (WHO)
Legal status
Legal status	In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	100% (IM)
Protein binding	95 to 99%
Metabolism	Hepatic
Elimination half-life	15 minutes to convert to phenytoin
Excretion	Renal (as phenytoin)
Identifiers
IUPAC name (2,5-dioxo-4,4-diphenyl-imidazolidin-1-yl)methoxyphosphonic acid
CAS Number	93390-81-9
PubChem CID	56339
DrugBank	APRD00241
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C16H15N2O6P
Molar mass	362.274 g/mol

Fosphenytoin (Cerebyx®, Parke-Davis; Prodilantin®, 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.

Uses

Approved

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.

Unapproved/off-label/investigational

In April of 2003, Applebaum and colleagues at the Ben-Gurion University of the Negev in Beersheba 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.

Metabolism

One mmol (millimole) of phenytoin is produced for every mmol 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 phenytoin, except that fosphenytoin causes less hypotension and more paresthesia. 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 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.

See also

• hydantoin
• ethotoin
• mephenytoin
• phenytoin