Pharmacotherapeutic group: Antivirals for systemic use; direct-acting antivirals; phosphonic acid derivatives, ATC code: J05AD01.
Foscarnet sodium hexahydrate is an antiviral agent with a broad spectrum inhibiting all known human viruses of the herpes group: herpes simplex virus type 1 and 2, human herpes virus 6, varicella zoster virus, Epstein-Barr virus and cytomegalovirus (CMV) and some retroviruses, including human immunodeficiency virus (HIV) at concentrations not affecting normal cell growth. Foscarnet sodium hexahydrate also inhibits the viral DNA polymerase from hepatitis B virus.
Foscarnet sodium hexahydrate exerts its antiviral activity by a direct inhibition of viral specific DNA polymerase a reverse transcriptase at concentrations that do not affect cellular DNA polymerases. Foscarnet sodium hexahydrate does not require activation (phosphorylation) by thymidine kinase or other kinases and therefore is active
in vitro
against HSV mutants deficient in thymidine kinase. CMV strains resistant to ganciclovir may be sensitive to foscarnet sodium hexahydrate. Sensitivity test results expressed as concentration of the drug required to inhibit growth of virus by 50% in cell culture (IC
50
) vary greatly depending on the assay method used and cell type employed. A number of sensitive viruses and their IC
50
are listed below.
Table 3: Foscarnet sodium hexahydrate inhibition of virus multiplication cell culture
Virus
IC
50
(µm)
CMV
50-800*
HSV-1, HSV-2
10-130
VZV
48-90
EBV
<500**
HHV-6
49
Ganciclovir resistant CMV
190
HSV-TK Minus mutant
67
HSV-DNA Polymerase mutant
5-443
HIV-1
11-32
Zidovudine-resistant HIV-1
10-32
* Mean = 269 micrograms
** 97% of viral antigen synthesis inhibited at 500 micrograms
If no clinical response to foscarnet sodium hexahydrate is observed, viral isolates should be tested for sensitivity to foscarnet sodium hexahydrate since naturally resistant mutants may exist or emerge under selective pressure both
in vitro
and
in vivo
.
The mean foscarnet sodium hexahydrate 50% inhibition value for more than one hundred clinical CMV isolates was approximately 270 micrograms/L, while a reversible inhibition of normal cell growth was observed at about 1000 micrograms/L.
There is no evidence of an increased myelotoxicity when foscarnet sodium hexahydrate is used in combination with zidovudine (AZT).
⚠️ Warnings
Individually dispensed doses of foscarnet sodium hexahydrate can be aseptically transferred to plastic infusion bags by the hospital pharmacy. The physico-chemical stability of foscarnet and dilutions thereof in equal parts with 0.9% sodium chloride (9 mg/ml) or 5% glucose (50 mg/ml) in PVC bags is 36 hours at 2-8°C and 20-25°C. However, diluted solutions should be refrigerated and storage restricted to 24 hours.
Each bottle of Foscarnet should only be used to treat one patient with a single infusion.
Accidental skin and eye contact with the foscarnet sodium hexahydrate solution may cause local irritation and burning sensation. If accidental contact occurs, the exposed area should be rinsed with water.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
