Foscarnet

drugbox
IUPAC_name = phosphonomethanoic acid

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CAS_number = 63585-09-1
ATC_prefix = J05
ATC_suffix = AD01
PubChem = 3415
DrugBank = APRD00669
C = 1 |H = 3 |O = 5 |P = 1
molecular_weight = 126.005 g/mol
300.1 g/mol (foscarnet trisodium hexahydrate)
bioavailability = NA
protein_bound = 14-17%
metabolism =
elimination_half-life = 3.3-6.8 hours
pregnancy_category = B3 (Au), C (U.S.)
legal_status = ℞-only (U.S.), POM (UK)
routes_of_administration = Intravenous

Foscarnet is the conjugate base of the chemical compound with the formula HO₂CPO₃H₂. This phosphonic acid derivative (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. [cite journal |author=Canestri A, Ghosn J, Wirden M, "et al" |title=Foscarnet salvage therapy for patients with late-stage HIV disease and multiple drug resistance |journal=Antivir. Ther. (Lond.) |volume=11 |issue=5 |pages=561–6 |year=2006 |pmid=16964823 |doi=] [cite journal |author=Mathiesen S, Dam E, Roge B, "et al" |title=Long-term foscarnet therapy remodels thymidine analogue mutations and alters resistance to zidovudine and lamivudine in HIV-1 |journal=Antivir. Ther. (Lond.) |volume=12 |issue=3 |pages=335–43 |year=2007 |pmid=17591023 |doi=] [cite journal |author=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=J. Mol. Biol. |volume=369 |issue=1 |pages=41–54 |year=2007 |pmid=17400246 |doi=10.1016/j.jmb.2007.03.006 |url=http://linkinghub.elsevier.com/retrieve/pii/S0022-2836(07)00335-X]

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.cite journal |author=Bonnafous P, Naesens L, Petrella S, "et al" |title=Different mutations in the HHV-6 DNA polymerase gene accounting for resistance to foscarnet |journal=Antivir. Ther. (Lond.) |volume=12 |issue=6 |pages=877–88 |year=2007 |pmid=17926642 |doi=]

Administration

Intravenous only

ide 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.

References