{{Short description|Chemical compound}} {{Drugbox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 461113374 | IUPAC_name = phosphonoformic acid | image = Foscarnet.svg | image_class = skin-invert-image | width = 160 | image2 = Foscarnet ball-and-stick model.png | image_class2 = bg-transparent
<!--Clinical data--> | tradename = Foscavir, Vocarvi, others | Drugs.com = {{drugs.com|monograph|foscarnet-sodium}} | MedlinePlus = a601144 | DailyMedID = Foscarnet | pregnancy_AU = B3 | pregnancy_category = | routes_of_administration = Intravenous | ATC_prefix = J05 | ATC_suffix = AD01
| legal_AU = S4 | legal_CA = Rx only | legal_CA_comment = <ref>{{cite web | title=Regulatory Decision Summary - Vocarvi | website=Health Canada | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/regulatory-decision-summary-detail.php?lang=en&linkID=RDS00819 | access-date=4 June 2022}}</ref> | legal_UK = POM | legal_US = Rx only | legal_US_comment = <ref name="Foscavir FDA label">{{cite web | title=Foscavir- foscarnet sodium injection, solution | website=DailyMed | date=23 April 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=90e3da4e-3b1f-428b-99ca-e4bed1c80028 | access-date=6 November 2020}}</ref> | legal_status =
<!--Pharmacokinetic data--> | bioavailability = NA | protein_bound = 14–17% | metabolism = | elimination_half-life = 3.3–6.8 hours
<!--Identifiers--> | IUPHAR_ligand = 5497 | CAS_number_Ref = {{cascite|changed|CAS}} | CAS_number = 4428-95-9 | CAS_supplemental = (trisodium salt) | PubChem = 3415 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB00529 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 3297 | UNII_Ref = {{fdacite|changed|FDA}} | UNII = 364P9RVW4X | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D00579 | KEGG2_Ref = {{keggcite|correct|kegg}} | KEGG2 = D02267 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 127780 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 666 | synonyms = phosphonomethanoic acid, dihydroxyphosphinecarboxylic acid oxide
<!--Chemical data--> | C=1 | H=3 | O=5 | P=1 | SMILES = O=C(O)P(=O)(O)O | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/CH3O5P/c2-1(3)7(4,5)6/h(H,2,3)(H2,4,5,6) | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = ZJAOAACCNHFJAH-UHFFFAOYSA-N }}
'''Foscarnet''' (phosphonomethanoic acid), known by its brand name '''Foscavir''', is an antiviral medication which is primarily used to treat viral infections involving the Herpesviridae family. It is classified as a pyrophosphate analog DNA polymerase inhibitor.<ref>{{cite journal | vauthors = Wagstaff AJ, Bryson HM | title = Foscarnet. A reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic use in immunocompromised patients with viral infections | journal = Drugs | volume = 48 | issue = 2 | pages = 199–226 | date = August 1994 | pmid = 7527325 | doi = 10.2165/00003495-199448020-00007 | s2cid = 260483894 }}</ref><ref>{{cite journal | vauthors = Chrisp P, Clissold SP | title = Foscarnet. A review of its antiviral activity, pharmacokinetic properties and therapeutic use in immunocompromised patients with cytomegalovirus retinitis | journal = Drugs | volume = 41 | issue = 1 | pages = 104–129 | date = January 1991 | pmid = 1706982 | doi = 10.2165/00003495-199141010-00009 | doi-access = free }}</ref> Foscarnet is the conjugate base of a chemical compound with the formula HO<sub>2</sub>CPO<sub>3</sub>H<sub>2</sub> (Trisodium phosphonoformate).<ref name=":0">{{cite book | vauthors = Garikapati S, Nguyen M | chapter = Foscarnet |date=2022 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK556108/ | title = StatPearls |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=32310568 |access-date=2022-04-04 }}</ref><ref>{{Cite web |title=phosphonoformic acid (CHEBI:127780) |url=https://www.ebi.ac.uk/chebi/searchId.do;jsessionid=70C5A36CC67C31A173436B68C83C5852?chebiId=CHEBI:127780 |access-date=2022-04-04 |website=www.ebi.ac.uk}}</ref>
Foscarnet was approved for medical use in 1991.<ref>{{cite book| vauthors= Long SS, Pickering LK, Prober CG |title=Principles and Practice of Pediatric Infectious Disease|date=2012|publisher=Elsevier Health Sciences|isbn=978-1-4377-2702-9|page=1502|url=https://books.google.com/books?id=nQ7-o8JAH7kC&pg=PA1502|language=en}}</ref> It is available as a generic medication.<ref>{{cite web | title=Competitive Generic Therapy Approvals | website=U.S. Food and Drug Administration (FDA) | date=29 June 2023 | url=https://www.fda.gov/drugs/generic-drugs/competitive-generic-therapy-approvals | access-date=29 June 2023 | archive-date=29 June 2023 | archive-url=https://web.archive.org/web/20230629233651/https://www.fda.gov/drugs/generic-drugs/competitive-generic-therapy-approvals | url-status=live }}</ref>
==Medical use== This phosphonic acid derivative (marketed by Clinigen as foscarnet sodium under the trade name Foscavir) is an antiviral medication used to treat herpes viruses, including drug-resistant cytomegalovirus (CMV) and herpes simplex viruses types 1 and 2 (HSV-1 and HSV-2). It is particularly used to treat CMV retinitis. Foscarnet can be used to treat highly treatment-experienced patients with HIV as part of salvage therapy.<ref>{{cite journal | vauthors = Canestri A, Ghosn J, Wirden M, Marguet F, Ktorza N, Boubezari I, Dominguez S, Bossi P, Caumes E, Calvez V, Katlama C | display-authors = 6 | title = Foscarnet salvage therapy for patients with late-stage HIV disease and multiple drug resistance | journal = Antiviral Therapy | volume = 11 | issue = 5 | pages = 561–566 | year = 2006 | pmid = 16964823 | doi = 10.1177/135965350601100501 | s2cid = 24905247 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Mathiesen S, Dam E, Roge B, Joergensen LB, Laursen AL, Gerstoft J, Clavel F | title = Long-term foscarnet therapy remodels thymidine analogue mutations and alters resistance to zidovudine and lamivudine in HIV-1 | journal = Antiviral Therapy | volume = 12 | issue = 3 | pages = 335–343 | year = 2007 | pmid = 17591023 | doi = 10.1177/135965350701200310 | s2cid = 19856772 | doi-access = free }}</ref><ref name="pmid17400246"/>
==Mechanism of action== Foscarnet is a structural mimic of the anion pyrophosphate that selectively inhibits the pyrophosphate binding site on viral DNA polymerases at concentrations that do not affect human DNA polymerases.<ref name="pmid17400246">{{cite journal | vauthors = Meyer PR, Rutvisuttinunt W, Matsuura SE, So AG, Scott WA | title = Stable complexes formed by HIV-1 reverse transcriptase at distinct positions on the primer-template controlled by binding deoxynucleoside triphosphates or foscarnet | journal = Journal of Molecular Biology | volume = 369 | issue = 1 | pages = 41–54 | date = May 2007 | pmid = 17400246 | pmc = 1986715 | doi = 10.1016/j.jmb.2007.03.006 }}</ref>
In individuals treated with the DNA polymerase inhibitors acyclovir or ganciclovir, HSV or CMV particles can develop mutant protein kinases (thymidine kinase or UL97 protein kinase, respectively) that make them resistant to these antiviral drugs.<ref>{{cite journal | vauthors = Chou S | title = Cytomegalovirus UL97 mutations in the era of ganciclovir and maribavir | journal = Reviews in Medical Virology | volume = 18 | issue = 4 | pages = 233–246 | date = July 2008 | pmid = 18383425 | doi = 10.1002/rmv.574 | s2cid = 42775774 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Frobert E, Ooka T, Cortay JC, Lina B, Thouvenot D, Morfin F | title = Herpes simplex virus thymidine kinase mutations associated with resistance to acyclovir: a site-directed mutagenesis study | journal = Antimicrobial Agents and Chemotherapy | volume = 49 | issue = 3 | pages = 1055–1059 | date = March 2005 | pmid = 15728902 | pmc = 549244 | doi = 10.1128/aac.49.3.1055-1059.2005 }}</ref> However, unlike acyclovir and ganciclovir, foscarnet is not activated by viral protein kinases, making it useful in acyclovir- or ganciclovir-resistant HSV and CMV infections.<ref name=":0" />
However, acyclovir- or ganciclovir-resistant mutants with alterations in viral DNA polymerase may also be resistant to foscarnet.<ref name="pmid17926642">{{cite journal | vauthors = Bonnafous P, Naesens L, Petrella S, Gautheret-Dejean A, Boutolleau D, Sougakoff W, Agut H | title = Different mutations in the HHV-6 DNA polymerase gene accounting for resistance to foscarnet | journal = Antiviral Therapy | volume = 12 | issue = 6 | pages = 877–888 | year = 2007 | pmid = 17926642 | doi = 10.1177/135965350701200608 | s2cid = 24584000 | doi-access = free }}</ref><ref name="pmid16415021">{{cite journal | vauthors = Tchesnokov EP, Gilbert C, Boivin G, Götte M | title = Role of helix P of the human cytomegalovirus DNA polymerase in resistance and hypersusceptibility to the antiviral drug foscarnet | journal = Journal of Virology | volume = 80 | issue = 3 | pages = 1440–1450 | date = February 2006 | pmid = 16415021 | pmc = 1346920 | doi = 10.1128/JVI.80.3.1440-1450.2006 }}</ref>
==Administration== Foscarnet is administered by intravenous infusion or intravitreous injection.{{cn|date=November 2022}}
==Side effects== * Nephrotoxicity — increase in serum creatinine levels and renal injury can occur in patients receiving foscarnet.<ref name=":0" /><ref>{{cite journal | vauthors = Ota R, Hirata A, Noto K, Yokoyama S, Hosomi K, Takada M, Matsuoka H | title = Relationship between serum calcium and creatinine in hematopoietic stem cell transplantation patients treated with foscarnet | journal = International Journal of Clinical Pharmacology and Therapeutics | volume = 58 | issue = 5 | pages = 274–281 | date = May 2020 | pmid = 32101522 | doi = 10.5414/CP203650 | s2cid = 211537187 }}</ref> Other nephrotoxic drugs should be avoided. Nephrotoxicity is usually reversible and can be reduced by dosage adjustment and adequate hydration.<ref name=":1">{{cite journal | vauthors = Jacobson MA | title = Review of the toxicities of foscarnet | journal = Journal of Acquired Immune Deficiency Syndromes | volume = 5 | issue = Suppl 1 | pages = S11–S17 | date = 1992-01-01 | pmid = 1534839 | url = https://europepmc.org/article/med/1534839 }}</ref> * Electrolyte disturbances — hypocalcemia and hypomagnesemia can occur<ref name=":1" /><ref>{{cite journal | vauthors = Gearhart MO, Sorg TB | title = Foscarnet-induced severe hypomagnesemia and other electrolyte disorders | journal = The Annals of Pharmacotherapy | volume = 27 | issue = 3 | pages = 285–289 | date = March 1993 | pmid = 8384030 | doi = 10.1177/106002809302700304 | s2cid = 37250222 }}</ref> and regular monitoring of electrolytes is necessary to avoid clinical toxicity.<ref name=":0" /><ref name=":2">{{cite journal | vauthors = Zareifopoulos N, Lagadinou M, Karela A, Kyriakopoulou O, Velissaris D | title = Neuropsychiatric Effects of Antiviral Drugs | journal = Cureus | volume = 12 | issue = 8 | article-number = e9536 | date = August 2020 | pmid = 32905132 | pmc = 7465925 | doi = 10.7759/cureus.9536 | doi-access = free }}</ref> * Genital ulceration — a less common reported side effect which occurs more in men and usually during induction use of foscarnet.<ref name=":0" /> It is most likely a contact dermatitis due to high concentrations of foscarnet in urine. It usually resolves rapidly following discontinuation of the drug.<ref>{{cite journal | vauthors = Adalsteinsson JA, Pan M, Kaushik S, Ungar J | title = Foscarnet-induced genital lesions: An overview with a case report | journal = Dermatology Reports | volume = 10 | issue = 1 | page = 7749 | date = April 2018 | pmid = 29991980 | pmc = 6026811 | doi = 10.4081/dr.2018.7749 }}</ref> * CNS — less common side effects of perioral paresthesia, irritability and altered mental states.<ref name=":2" />
== References == {{Reflist}}
==Sources== * Dennis L. Kasper, Eugene Braunwald. "[https://www.amazon.com/Harrisons-Principles-Internal-Medicine-16th/dp/0071402357 Harrison's Manual of Medicine]", 16th Edition, Mcgraw-hill, (2005), p. 2244.
== External links == * {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/foscarnet | archive-url = https://web.archive.org/web/20180827212444/https://druginfo.nlm.nih.gov/drugportal/name/Foscarnet | archive-date = August 27, 2018 | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Foscarnet }} * {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/rn/63585-09-1 | archive-url = https://web.archive.org/web/20190628201524/https://druginfo.nlm.nih.gov/drugportal/rn/63585-09-1 | archive-date = June 28, 2019 | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Foscarnet sodium }}
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Category:Anti-herpes virus drugs Category:Antiretroviral drugs Category:Phosphonic acids Category:Drugs developed by AstraZeneca Category:Carboxylic acids Category:Nephrotoxins