Fosphenytoin

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Fosphenytoin
Fosphenytoin.svg
Fosphenytoin 3D ball.png
Clinical data
Trade names Cerebyx, others
AHFS/Drugs.com Monograph
MedlinePlus a604036
License data
Routes of
administration 		Intravenous, intramuscular
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 100% (IM)
Protein binding 95–99%
Metabolism Liver
Elimination half-life 15 minutes to convert to phenytoin
Excretion Kidney (as phenytoin)
Identifiers
  • (2,5-Dioxo-4,4-diphenyl-imidazolidin-1-yl)methoxyphosphonic acid
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C16H15N2O6P
Molar mass 362.278 g·mol−1
3D model (JSmol)
  • O=C3N(C(=O)C(c1ccccc1)(c2ccccc2)N3)COP(=O)(O)O
  • InChI=1S/C16H15N2O6P/c19-14-16(12-7-3-1-4-8-12,13-9-5-2-6-10-13)17-15(20)18(14)11-24-25(21,22)23/h1-10H,11H2,(H,17,20)(H2,21,22,23) Yes check.svgY
  • Key:XWLUWCNOOVRFPX-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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.

Contents

Fosphenytoin was developed in 1996. [3]

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, [4] 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. [5]

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. [6]

Metabolism

One milli mole 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. [4]

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. [7]

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. [8] 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. [9] 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. [10]

References

  1. ↑ "Cerebyx Product information". Health Canada . 7 October 2022. Retrieved 16 February 2025.
  2. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA . Retrieved 22 October 2023.
  3. ↑ Pitkänen A, Schwartzkroin PA, Moshé SL (2005). Models of Seizures and Epilepsy. Burlington: Elsevier. p. 539. ISBN   9780080457024.
  4. 1 2 Parke-Davis (2001). "Cerebyx: Fosphenytoin Sodium Injection - Labeling Revision" (PDF). Cerebyx Approval History. Warner-Lambert Company. Archived from the original (PDF) on 17 October 2003. Retrieved 20 October 2005.
  5. ↑ Johnson J, Wrenn K (2001). "Inappropriate fosphenytoin use in the ED". American Journal of Emergency Medicine. 19 (4): 293–4. doi:10.1053/ajem.2001.24471. PMID   11447516.
  6. ↑ Applebaum J, Levine J, Belmaker RH (2003). "Intravenous fosphenytoin in acute mania". Journal of Clinical Psychiatry. 64 (4): 408–9. doi:10.4088/JCP.v64n0408. PMID   12716241.
  7. ↑ McBryde KD, Wilcox J, Kher KK (2005). "Hyperphosphatemia due to fosphenytoin in a pediatric ESRD patient". Pediatric Nephrology (Berlin, Germany). 20 (8): 1182–5. doi:10.1007/s00467-005-1947-0. PMID   15965770. S2CID   6664220.
  8. ↑ Yamaoka Y, Roberts RD, Stella VJ (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. 72 (4): 400–5. doi:10.1002/jps.2600720420. PMID   6864479.
  9. ↑ Tuen C. "Anticonvulsants before 1993". Neuroland. Archived from the original on 4 August 2019.
  10. ↑ "Cerebyx Approval History" (PDF). Retrieved 20 October 2005.
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