Foscarnet

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Foscarnet
Systematic (IUPAC) name
phosphonomethanoic acid
Identifiers
CAS number	63585-09-1
ATC code	J05AD01
PubChem	3415
DrugBank	APRD00669
Chemical data
Formula	C H₃O₅P
Mol. mass	126.005 g/mol 300.1 g/mol (foscarnet trisodium hexahydrate)
Pharmacokinetic data
Bioavailability	NA
Protein binding	14-17%
Metabolism	?
Half life	3.3-6.8 hours
Excretion	?
Therapeutic considerations
Pregnancy cat.	B3 (Au), C (U.S.)
Legal status	℞-only (U.S.), POM (UK)
Routes	Intravenous

Foscarnet is the conjugate base of the chemical compound with the formula HO₂CPO₃H₂. This phosphonic acid derivative is (marketed by AstraZeneca as foscarnet sodium under the trade name Foscavir) is an antiviral medication used to treat herpes viruses, including 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.^[1]^[2]^[3]

1 Mechanism of action
2 Administration
3 Side effects
4 References

[edit] 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. Because foscarnet is not activated by thymidine kinase, it maintains activity in some viruses which have lost thymidine kinase activity to gain resistance to acyclovir or ganciclovir. Therefore, foscarnet is often used in acyclovir- or ganciclovir-resistant disease.

However, acyclovir or ganciclovir resistant mutants with alterations in viral DNA polymerase may be resistant to foscarnet.^[4]

[edit] Administration

Intravenous only

[edit] 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, 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.

[edit] References

^ 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.
^ 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.
^ 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. PMID 17400246.
^ 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.

v • d • e Antivirals, other than for HIV (primarily J05, also S01AD and D06BB)

Anti-herpesvirus (DNA, I)	guanine analogues (Aciclovir, Famciclovir, Ganciclovir, Penciclovir, Valaciclovir, Valganciclovir) • nucleoside analogues (Idoxuridine, Trifluridine, Vidarabine) • Cidofovir • Docosanol • Fomivirsen • Foscarnet • Tromantadine

HPV/MC (DNA, I)	Imiquimod • Podophyllotoxin

Hepatitis B (DNA, VII)	Adefovir • Clevudine • Interferon alfa-2b • Pegylated interferon alfa-2a • Entecavir • Lamivudine • Telbivudine • Tenofovir^†

Hepatitis C (RNA, IV)	Pegylated interferon alpha • Ribavirin • Taribavirin^† • Boceprevir^†

Picornavirus (RNA, IV)	Pleconaril^†

Anti-influenza agents (RNA, V)	Arbidol adamantane derivatives/M2 inhibitors (Amantadine, Rimantadine) neuraminidase inhibitors (Oseltamivir, Zanamivir, Peramivir^†)

HIV (Reverse, VI)	See HIV pharm

Other antiviral agents	general (Inosine, Interferon)

^†Undergoing clinical trials, not FDA approved.

v • d • e Antivirals used against HIV (HAART) (primarily J05)

Nucleoside & Nucleotide Reverse Transcriptase Inhibitors (NRTI)	Abacavir (ABC)° • Emtricitabine° • Lamivudine (3TC)° • Tenofovir° • Didanosine • Zidovudine (AZT) • Apricitabine^† • Stampidine^† • Elvucitabine^† • Racivir^† • Amdoxovir^† • Stavudine^‡ • Zalcitabine^‡

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI)	Efavirenz° • Nevirapine • Etravirine • Rilpivirine^† • Loviride^‡ • Delavirdine^‡

Protease Inhibitors (PI)	Atazanavir° • Brecanavir^§ • Fosamprenavir° • Lopinavir° • Darunavir • Nelfinavir • Ritonavir • Saquinavir • Tipranavir • Amprenavir^‡ • Indinavir^‡

Entry/fusion inhibitors	Enfuvirtide • Maraviroc • Vicriviroc^† • PRO 140^† • Ibalizumab^†

Integrase inhibitors	Raltegravir • Elvitegravir^†

Maturation inhibitors	Bevirimat^† • Vivecon™^†

Combined formulations	Combivir • Atripla • Trizivir • Truvada • Kaletra • Epzicom

Other & experimental agents	Foscarnet • Hydroxyurea • Synergistic enhancers • Epigallocatechin gallate • Portmanteau inhibitors • Globoidnan A • Griffithsin • Diarylpyrimidines • Calanolide A • Cyanovirin-N • Miltefosine • R-roscovitine^†

°DHHS preferred first-line agent. ^†Undergoing clinical trials, not FDA approved. ^‡Formerly or rarely used agent. ^§Development terminated.