Foscarnet

Foscarnet

Clinical data
Trade names	Foscavir
AHFS/Drugs.com	Monograph
MedlinePlus	a601144
Pregnancy category	B3 (Au), C (U.S.)
Routes of administration	Intravenous
ATC code	J05AD01 (WHO)
Legal status
Legal status	℞-only (U.S.), POM (UK)
Pharmacokinetic data
Bioavailability	NA
Protein binding	14-17%
Biological half-life	3.3-6.8 hours
Identifiers
IUPAC name phosphonoformic acid
Synonyms	phosphonomethanoic acid, dihydroxyphosphinecarboxylic acid oxide
CAS Number	4428-95-9 (trisodium salt)
PubChem (CID)	3415
IUPHAR/BPS	5497
DrugBank	DB00529
ChemSpider	3297
UNII	364P9RVW4X
KEGG	C06456
ChEBI	CHEBI:127780
ChEMBL	CHEMBL666
ECHA InfoCard	100.224.300
Chemical and physical data
Formula	CH3O5P
Molar mass	126.005 g/mol 300.1 g/mol (foscarnet trisodium hexahydrate)
3D model (Jmol)	Interactive image
SMILES O=C(O)P(=O)(O)O
InChI InChI=1S/CH3O5P/c2-1(3)7(4,5)6/h(H,2,3)(H2,4,5,6) Key:ZJAOAACCNHFJAH-UHFFFAOYSA-N
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Foscarnet is the conjugate base of the chemical compound with the formula HO₂CPO₃H₂. Foscarnet sodium is used as an antiviral medication.

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 ganciclovir-resistant HSV and CMV infections.

However, acyclovir- or ganciclovir-resistant 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

External links

• Foscavir full prescribing information

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 1437727026.
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 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.
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 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.
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.80.3.1440-1450.2006. PMC 1346920. PMID 16415021.

• Harrison Tectbook of Medicine 16th ed, page 2244