Foscarnet - Wikipedia PDF

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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. Foscarnet is the conjugate base of a chemical compound with the formula HO2CPO3H2.

Foscarnet

Clinical data Trade names Other names

Foscavir phosphonomethanoic acid, dihydroxyphosphinecarboxylic acid oxide

AHFS/Drugs.com

Monograph

MedlinePlus

a601144

Pregnancy category

AU: B3

US: C (Risk not ruled Routes of administration

out) Intravenous

ATC code

J05AD01 (WHO ) Legal status

Legal status

UK: POM (Prescription only) US: ℞-only

Pharmacokinetic data Bioavailability

NA

Protein binding

14–17%

Elimination half-life

3.3–6.8 hours

Identifiers

IUPAC name

CAS Number phosphonoform ic ac id

4428-95-9

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(trisodium salt) PubChem CID

3415

IUPHAR/BPS

5497

DrugBank

DB00529

ChemSpider

3297

UNII

364P9RVW4X

KEGG

C06456

ChEBI

CHEBI:127780

ChEMBL

ChEMBL666

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

 

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CompTox Dashboard DTXSID0048478 (EPA) Chemical and physical data Formula

CH3O5P

Molar mass

126.005 g/mol 300.1 g/mol (foscarnet trisodium hexahydrate)g·mol−1

3D model (JSmol)

Interactive image

SMILES O=C(O)P (=O)(O)O

InChI InChI=1S /CH3O5P/c 2-1(3)7(4,5)6/h(H,2,3)(H2,4,5,6) Key:ZJAOAACCNHFJAH-UHFFFAOYS A-N

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Foscarnet was approved for medical use in 1991.[1]

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.[2][3][4]

Mechanism of action

Foscarnet is a structural mimic of the anion pyrophosphate[5] that selectively inhibits the pyrophosphate binding site on viral DNA polymerases at concentrations that do not affect human DNA polymerases. 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. However, unlike acyclovir and ganciclovir, foscarnet is not activated by viral protein kinases, making

it useful in acyclovir- or ganciclovirresistant HSV and CMV infections. However, acyclovir- or ganciclovirresistant mutants with alterations in viral DNA polymerase may also be resistant to foscarnet.[6][7]

Administration Intravenous infusion or intravitreous injection.

Side effects Nephrotoxicity—Increase in serum creatinine levels occurs on average in

45% of patients receiving foscarnet. Other nephrotoxic drugs should be avoided. Nephrotoxicity is usually reversible and can be reduced by dosage adjustment and adequate hydration. Electrolyte disturbances—Changes in calcium, magnesium (Harisson 16th ed page2244) potassium and phosphate levels occurs commonly and regular monitoring of electrolytes is necessary to avoid clinical toxicity. Genital ulceration—Occurs more commonly in men and usually occurs during induction use of foscarnet. It is

most likely a contact dermatitis due to high concentrations of foscarnet in urine. It usually resolves rapidly following discontinuation of the drug. CNS—Paraesthesias, irritability and hallucinations.

References 1. 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.

2. 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. PMID16964823 . 3. 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. PMID17591023 . 4. Meyer PR, Rutvisuttinunt W, Matsuura SE, So AG, Scott WA

(2007). "Stable complexes formed by HIV-1 reverse transcriptase at distinct positions on the primertemplate 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 . 5. 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 primertemplate 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 . 6. 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. PMID17926642 . 7. 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.80.3.14401450.2006 . PMC1346920 . PMID16415021 .

Sources Harrison Textbook of Medicine 16th ed, page 2244

External links Foscavir full prescribing information

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