Foscarnet
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Trade names | Foscavir, Vocarvi, others |
Other names | phosphonomethanoic acid, dihydroxyphosphinecarboxylic acid oxide |
AHFS/Drugs.com | Monograph |
MedlinePlus | a601144 |
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Routes of administration | Intravenous |
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Bioavailability | NA |
Protein binding | 14–17% |
Elimination half-life | 3.3–6.8 hours |
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Chemical and physical data | |
Formula | CH3O5P |
Molar mass | 126.004 g·mol−1 |
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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.[3][4] Foscarnet is the conjugate base of a chemical compound with the formula HO2CPO3H2 (Trisodium phosphonoformate).[5][6]
Foscarnet was approved for medical use in 1991.[7]
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.[8][9][10]
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.[11]
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.[12][13] 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.[5]
However, acyclovir- or ganciclovir-resistant mutants with alterations in viral DNA polymerase may also be resistant to foscarnet.[14][15]
Administration
Foscarnet is administered by intravenous infusion or intravitreous injection.[citation needed]
Side effects
- Nephrotoxicity — increase in serum creatinine levels and renal injury can occur in patients receiving foscarnet.[5][16] Other nephrotoxic drugs should be avoided. Nephrotoxicity is usually reversible and can be reduced by dosage adjustment and adequate hydration.[17]
- Electrolyte disturbances — hypocalcemia and hypomagnesemia can occur[17][18] and regular monitoring of electrolytes is necessary to avoid clinical toxicity.[5][19]
- Genital ulceration — a less common reported side effect which occurs more in men and usually during induction use of foscarnet.[5] It is most likely a contact dermatitis due to high concentrations of foscarnet in urine. It usually resolves rapidly following discontinuation of the drug.[20]
- CNS — less common side effects of perioral paresthesia, irritability and altered mental states.[19]
References
- ^ "Regulatory Decision Summary - Vocarvi". Health Canada. 23 October 2014. Retrieved 4 June 2022.
- ^ "Foscavir- foscarnet sodium injection, solution". DailyMed. 23 April 2020. Retrieved 6 November 2020.
- ^ Wagstaff, Antona J.; Bryson, Harriet M. (1994-08-01). "Foscarnet". Drugs. 48 (2): 199–226. doi:10.2165/00003495-199448020-00007. ISSN 1179-1950. PMID 7527325.
- ^ Chrisp, Paul; Clissold, Stephen P. (1991-01-01). "Foscarnet". Drugs. 41 (1): 104–129. doi:10.2165/00003495-199141010-00009. ISSN 1179-1950. PMID 1706982.
- ^ a b c d e Garikapati, Sriram; Nguyen, Minhthao (2022), "Foscarnet", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 32310568, retrieved 2022-04-04
- ^ "phosphonoformic acid (CHEBI:127780)". www.ebi.ac.uk. Retrieved 2022-04-04.
- ^ Long, Sarah S.; Pickering, Larry K.; Prober, Charles G. (2012). Principles and Practice of Pediatric Infectious Disease. Elsevier Health Sciences. p. 1502. ISBN 978-1437727029.
- ^ Canestri A, Ghosn J, Wirden M, et al. (2006). "Foscarnet salvage therapy for patients with late-stage HIV disease and multiple drug resistance". Antivir. Ther. (Lond.). 11 (5): 561–6. doi:10.1177/135965350601100501. PMID 16964823. S2CID 24905247.
- ^ Mathiesen S, Dam E, Roge B, et al. (2007). "Long-term foscarnet therapy remodels thymidine analogue mutations and alters resistance to zidovudine and lamivudine in HIV-1". Antivir. Ther. (Lond.). 12 (3): 335–43. doi:10.1177/135965350701200310. PMID 17591023. S2CID 19856772.
- ^ Meyer PR, Rutvisuttinunt W, Matsuura SE, So AG, Scott WA (2007). "Stable complexes formed by HIV-1 reverse transcriptase at distinct positions on the primer-template controlled by binding deoxynucleoside triphosphates or foscarnet". J. Mol. Biol. 369 (1): 41–54. doi:10.1016/j.jmb.2007.03.006. PMC 1986715. PMID 17400246.
- ^ Meyer PR, Rutvisuttinunt W, Matsuura SE, So AG, Scott WA (May 2007). "Stable complexes formed by HIV-1 reverse transcriptase at distinct positions on the primer-template controlled by binding deoxynucleoside triphosphates or foscarnet". J. Mol. Biol. 369 (1): 41–54. doi:10.1016/j.jmb.2007.03.006. PMC 1986715. PMID 17400246.
- ^ Chou, Sunwen (July 2008). "Cytomegalovirus UL97 mutations in the era of ganciclovir and maribavir". Reviews in Medical Virology. 18 (4): 233–246. doi:10.1002/rmv.574. ISSN 1052-9276. PMID 18383425. S2CID 42775774.
- ^ Frobert, E.; Ooka, T.; Cortay, J. C.; Lina, B.; Thouvenot, D.; Morfin, F. (March 2005). "Herpes Simplex Virus Thymidine Kinase Mutations Associated with Resistance to Acyclovir: a Site-Directed Mutagenesis Study". Antimicrobial Agents and Chemotherapy. 49 (3): 1055–1059. doi:10.1128/aac.49.3.1055-1059.2005. ISSN 0066-4804. PMC 549244. PMID 15728902.
- ^ Bonnafous P, Naesens L, Petrella S, et al. (2007). "Different mutations in the HHV-6 DNA polymerase gene accounting for resistance to foscarnet". Antivir. Ther. (Lond.). 12 (6): 877–88. doi:10.1177/135965350701200608. PMID 17926642. S2CID 24584000.
- ^ Tchesnokov EP, Gilbert C, Boivin G, Götte M (February 2006). "Role of helix P of the human cytomegalovirus DNA polymerase in resistance and hypersusceptibility to the antiviral drug foscarnet". J. Virol. 80 (3): 1440–50. doi:10.1128/JVI.80.3.1440-1450.2006. PMC 1346920. PMID 16415021.
- ^ Ota, Ryosuke; Hirata, Atsushi; Noto, Keisuke; Yokoyama, Satoshi; Hosomi, Kouichi; Takada, Mitsutaka; Matsuoka, Hiroshi (May 2020). "Relationship between serum calcium and creatinine in hematopoietic stem cell transplantation patients treated with foscarnet". International Journal of Clinical Pharmacology and Therapeutics. 58 (5): 274–281. doi:10.5414/CP203650. ISSN 0946-1965. PMID 32101522. S2CID 211537187.
- ^ a b Jacobson, M A (1992-01-01). "Review of the toxicities of foscarnet". Journal of Acquired Immune Deficiency Syndromes. 5 Suppl 1: S11–7. ISSN 0894-9255. PMID 1534839.
- ^ Gearhart, Maureen O.; Sorg, Timothy B. (March 1993). "Foscarnet-Induced Severe Hypomagnesemia and other Electrolyte Disorders". Annals of Pharmacotherapy. 27 (3): 285–289. doi:10.1177/106002809302700304. ISSN 1060-0280. PMID 8384030. S2CID 37250222.
- ^ a b Zareifopoulos, Nicholas; Lagadinou, Maria; Karela, Anastasia; Kyriakopoulou, Ourania; Velissaris, Dimitrios (2020-08-03). "Neuropsychiatric Effects of Antiviral Drugs". Cureus. 12 (8): e9536. doi:10.7759/cureus.9536. ISSN 2168-8184. PMC 7465925. PMID 32905132.
{{cite journal}}
: CS1 maint: unflagged free DOI (link) - ^ Adalsteinsson, Jonas A.; Pan, Michael; Kaushik, Shivani; Ungar, Jonathan (2018-06-20). "Foscarnet-induced genital lesions: An overview with a case report". Dermatology Reports. 10 (1): 7749. doi:10.4081/dr.2018.7749. ISSN 2036-7392. PMC 6026811. PMID 29991980.
Sources
- Dennis L. Kasper, Eugene Braunwald. "Harrison's Manual of Medicine", 16th Edition, Mcgraw-hill, (2005), p. 2244.
External links
- "Foscarnet". Drug Information Portal. U.S. National Library of Medicine.
- "Foscarnet sodium". Drug Information Portal. U.S. National Library of Medicine.