Fosphenytoin

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 anticonvulsants are often very effective in mania, and acute mania requires rapid treatment, fosphenytoin had no antimanic effect.

Metabolism

One millimole 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 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 US Food and Drug Administration (FDA) in August 1996, for use in epilepsy.

References

References

1. (7 October 2022). "Cerebyx Product information".
2. (2005). "Models of Seizures and Epilepsy.". Elsevier.
3. Parke-Davis. (2001). "Cerebyx: Fosphenytoin Sodium Injection - Labeling Revision". Warner-Lambert Company.
4. (2001). "Inappropriate fosphenytoin use in the ED". American Journal of Emergency Medicine.
5. (2003). "Intravenous fosphenytoin in acute mania". Journal of Clinical Psychiatry.
6. (2005). "Hyperphosphatemia due to fosphenytoin in a pediatric ESRD patient". Pediatric Nephrology (Berlin, Germany).
7. (April 1983). "Low-melting phenytoin prodrugs as alternative oral delivery modes for phenytoin: a model for other high-melting sparingly water-soluble drugs". J Pharm Sci.
8. "Anticonvulsants before 1993". Neuroland.
9. "Cerebyx Approval History".