Fosphenytoin

Fosphenytoin
Names
Trade namesCerebyx, others
Other namesFosphenytoin sodium[1]
IUPAC name
  • (2,5-Dioxo-4,4-diphenyl-imidazolidin-1-yl)methoxyphosphonic acid
Clinical data
Drug classAnticonvulsant
Main usesStatus epilepticus, prevent seizures[1]
Side effectsDizziness, nystagmus, itchiness, numbness, sleepiness, poor coordination[2]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • US: D (Evidence of risk)
    Routes of
    use    		Intravenous, intramuscular
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa604036
    Legal
    License data
    Legal status
    • US: ℞-only
    • In general: ℞ (Prescription only)
    Pharmacokinetics
    Bioavailability100% (IM)
    Protein binding95–99%
    MetabolismLiver
    Elimination half-life15 minutes to convert to phenytoin
    ExcretionKidney (as phenytoin)
    Chemical and physical data
    FormulaC16H15N2O6P
    Molar mass362.278 g·mol−1
    3D model (JSmol)
    SMILES
    • O=C3N(C(=O)C(c1ccccc1)(c2ccccc2)N3)COP(=O)(O)O
    InChI
    • 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) checkY
    • Key:XWLUWCNOOVRFPX-UHFFFAOYSA-N checkY

    Fosphenytoin, sold under the brand name Cerebyx among others, is a medication used to treat status epilepticus and prevent seizures.[1] It may be used instead of phenytoin in those who cannot take medication by mouth.[1] It is given by injection into a vein or muscle.[1]

    Common side effects include dizziness, nystagmus, itchiness, numbness, sleepiness, and poor coordination.[2] Other side effects may include low blood pressure, QT prolongation, Stevens-Johnson syndrome, angioedema, and liver problems.[2] Use in pregnancy may harm the baby.[3] It is a prodrug of phenytoin and works by blocking sodium channels.[1][2]

    Fosphenytoin was approved for medical use in the United States in 1996.[2] It is available as a generic medication.[2] In the United Kingdom a 750 mg vial costs the NHS about £40.[1] In the United States this amount costs about 24 USD.[4]

    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,[5] such as endotracheal intubation, status epilepticus or some other type of repeated seizures; cluster seizure ,vomiting, and the person is unalert or not awake or both.[6]

    Dosage

    For status epilepticus it may be given at an initial dose of 20 mg "phenytoin equivalent" (PE) per kilogram.[1] This is given at a rate of 100 to 150 mg PE per minute.[1]

    To determine PE 150 mg of fosphenytoin is equivalent to 100 mg of phenytoin.[1]

    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]

    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.[5]

    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 Food and Drug Administration (FDA) on August 5, 1996, for use in epilepsy.[10]

    Research

    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.[11]

    References

    1. 1 2 3 4 5 6 7 8 9 10 BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 332. ISBN 978-0857114105.
    2. 1 2 3 4 5 6 "Fosphenytoin Monograph for Professionals". Drugs.com. Archived from the original on 23 January 2021. Retrieved 13 December 2021.
    3. ↑ "Fosphenytoin Use During Pregnancy". Drugs.com. Archived from the original on 24 November 2020. Retrieved 13 December 2021.
    4. ↑ "Fosphenytoin Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 11 April 2021. Retrieved 13 December 2021.
    5. 1 2 Parke-Davis (2001). "Cerebyx: Fosphenytoin Sodium Injection - Labeling Revision" (PDF). Cerebyx Approval History. Warner-Lambert Company. Archived from the original (PDF) on October 17, 2003. Retrieved 20 October 2005.
    6. ↑ 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. Fulltext options Archived 2021-10-31 at the Wayback Machine List of Library Holdings Worldwide Archived 2021-10-31 at the Wayback Machine
    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. ↑ Anticonvulsants before 1993 Archived 2019-08-04 at the Wayback Machine Neuroland
    10. ↑ "Cerebyx Approval History". Archived from the original on 6 May 2016. Retrieved 20 October 2005.
    11. ↑ 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.
    External sites:
    Identifiers:
    • "Fosphenytoin sodium". Drug Information Portal. U.S. National Library of Medicine. Archived from the original on 2021-06-26. Retrieved 2021-08-26.
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