|Other names||Foscarnet sodium, phosphonomethanoic acid, dihydroxyphosphinecarboxylic acid oxide|
|Main uses||Cytomegalovirus (CMV), herpes simplex virus (HSV), varicella zoster virus (VZV)|
|Side effects||Fever, nausea, low red blood cells, kidney problems, seizures, headache|
|Elimination half-life||3.3–6.8 hours|
|Chemical and physical data|
|Molar mass||126.004 g·mol−1|
|3D model (JSmol)|
Foscarnet, sold under the brand name Foscavir, is an antiviral used to treat cytomegalovirus (CMV), herpes simplex virus (HSV), and varicella zoster virus (VZV). Primarily this is those who are immunocompromised such as due to HIV/AIDS. It is given by injection into a vein.
Common side effects include fever, nausea, low red blood cells, kidney problems, seizures, and headache. Other side effects may include electrolyte abnormalities, prolonged QT, and anaphylaxis. Safety in pregnancy is unclear. It acts similar to pyrophosphate as a viral DNA polymerase inhibitor.
Foscarnet was approved for medical use in the United States in 1991. In the United Kingdom 6 grams costs the NHS about £120 as of 2021. This amount in the United States cost about 4,800 USD.
It is 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.
Foscarnet is administered by intravenous infusion or intravitreous injection.
It is given at a dose of 60 mg/kg three times per day for CMV and 40 mg/kg three times per day for HSV.
- 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 — paresthesia, irritability and hallucinations.
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.
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.
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