Fosphenytoin
{{Short description|Anti-epileptic drug}}
{{Use dmy dates|date=February 2025}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 461113778
| image = Fosphenytoin.svg
| width = 175
| alt =
| image2 = Fosphenytoin 3D ball.png
| alt2 =
| tradename = Cerebyx, others
| Drugs.com = {{drugs.com|monograph|fosphenytoin-sodium}}
| MedlinePlus = a604036
| DailyMedID = Fosphenytoin
| routes_of_administration = Intravenous, intramuscular
| ATC_prefix = N03
| ATC_suffix = AB05
| legal_CA = Rx-only
| legal_CA_comment = {{cite web | title=Cerebyx Product information | website=Health Canada | date=7 October 2022 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=50269 | access-date=16 February 2025}}
| legal_US = Rx-only
| legal_status = Rx-only
| bioavailability = 100% (IM)
| protein_bound = 95–99%
| metabolism = Liver
| elimination_half-life = 15 minutes to convert to phenytoin
| excretion = Kidney (as phenytoin)
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 93390-81-9
| PubChem = 56339
| IUPHAR_ligand = 7190
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01320
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 50839
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = B4SF212641
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D07993
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 919
| IUPAC_name = (2,5-Dioxo-4,4-diphenyl-imidazolidin-1-yl)methoxyphosphonic acid
| C=16 | H=15 | N=2 | O=6 | P=1
| smiles = O=C3N(C(=O)C(c1ccccc1)(c2ccccc2)N3)COP(=O)(O)O
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = XWLUWCNOOVRFPX-UHFFFAOYSA-N
}}
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.
Fosphenytoin was developed in 1996.{{cite book| vauthors = Pitkänen A, Schwartzkroin PA, Moshé SL |title=Models of Seizures and Epilepsy.|date=2005|publisher=Elsevier|location=Burlington|isbn=9780080457024|page=539|url=https://books.google.com/books?id=Qw6KqLjwtZQC&pg=PA539}}
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,{{cite web|author=Parke-Davis |year=2001 |title=Cerebyx: Fosphenytoin Sodium Injection - Labeling Revision |work=Cerebyx Approval History |publisher=Warner-Lambert Company |url=https://www.fda.gov/cder/foi/label/2001/20450s4s5lbl.pdf |access-date=20 October 2005 |url-status=dead |archive-url=https://web.archive.org/web/20031017163732/https://www.fda.gov/CDER/foi/label/2001/20450s4s5lbl.pdf |archive-date=October 17, 2003 }} 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.{{cite journal |vauthors=Johnson J, Wrenn K | title=Inappropriate fosphenytoin use in the ED | journal=American Journal of Emergency Medicine | volume=19 | issue=4 | year=2001 | pages=293–4 | pmid=11447516 | doi=10.1053/ajem.2001.24471}}
= 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.{{cite journal | doi=10.4088/JCP.v64n0408 |vauthors=Applebaum J, Levine J, Belmaker RH | title=Intravenous fosphenytoin in acute mania | journal=Journal of Clinical Psychiatry | volume=64 | issue=4 | year=2003 | pages=408–9 | pmid=12716241 }}
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.{{cite journal |vauthors=McBryde KD, Wilcox J, Kher KK | title=Hyperphosphatemia due to fosphenytoin in a pediatric ESRD patient | journal=Pediatric Nephrology (Berlin, Germany) | volume=20 | issue=8 | year=2005 | pages=1182–5 | pmid=15965770 | doi=10.1007/s00467-005-1947-0| s2cid=6664220 }}
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.{{cite journal |vauthors=Yamaoka Y, Roberts RD, Stella VJ |title=Low-melting phenytoin prodrugs as alternative oral delivery modes for phenytoin: a model for other high-melting sparingly water-soluble drugs |journal=J Pharm Sci |volume=72 |issue=4 |pages=400–5 |date=April 1983 |pmid=6864479 |doi=10.1002/jps.2600720420 }} 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.{{cite web | vauthors = Tuen C | url = http://neuroland.com/sz/anticon/before_93.htm | title = Anticonvulsants before 1993 | work = Neuroland | archive-url = https://web.archive.org/web/20190804174151/https://neuroland.com/sz/anticon/before_93.htm | archive-date = 4 August 2019 }} 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.{{cite web | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020450Orig1s000rev.pdf | title=Cerebyx Approval History | access-date=20 October 2005 }}
References
{{Reflist}}
{{Anticonvulsants}}
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