Brands, Medical Use, Clinical Data
- Reverse Transcriptase Inhibitors
Brands / Synonyms
Carboxyphosphonic acid; Dihydroxyphosphinecarboxylic acid oxide; Forscarnet sodium; Foscarmet; Foscarnet; Foscarnet sodium; Foscavir; PFA; Phgosphonocarboxylic acid; Phosphonoformate; Phosphonoformic acid; Triapten
For the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS) and for treatment of acyclovir-resistant mucocutaneous HSV infections in immunocompromised patients.
Foscarnet is an organic analogue of inorganic pyrophosphate that inhibits replication of herpes viruses in vitro including cytomegalovirus (CMV) and herpes simplex virus types 1 and 2 (HSV-1 and HSV-2). Foscarnet does not require activation (phosphorylation) by thymidine kinase or other kinases and therefore is active in vitro against HSV TK deficient mutants and CMV UL97 mutants. Thus, HSV strains resistant to acyclovir or CMV strains resistant to ganciclovir may be sensitive to foscarnet. However, acyclovir or ganciclovir resistant mutants with alterations in the viral DNA polymerase may be resistant to foscarnet and may not respond to therapy with foscarnet. The combination of foscarnet and ganciclovir has been shown to have enhanced activity in vitro.
Mechanism of Action
Foscarnet exerts its antiviral activity by a selective inhibition at the pyrophosphate binding site on virus-specific DNA polymerases at concentrations that do not affect cellular DNA polymerases.
Poorly absorbed after oral administration (bioavailability from 12 to 22%).
Oral, rat LD50: >2,000 mg/kg. Signs of overdose include renal impairment.
Biotrnasformation / Drug Metabolism
FOSCAVIR is contraindicated in patients with clinically significant hypersensitivity to foscarnet sodium.
A possible drug interaction of FOSCAVIR and intravenous pentamidine has been described. Concomitant
treatment of four patients in the United Kingdom with FOSCAVIR and intravenous pentamidine may have caused
hypocalcemia; one patient died with severe hypocalcemia. Toxicity associated with concomitant use of aerosolized
pentamidine has not been reported.
Because of foscarnet's tendency to cause renal impairment, the use of FOSCAVIR should be avoided in combination
with potentially nephrotoxic drugs such as aminoglycosides, amphotericin B and intravenous pentamidine unless the
potential benefits outweigh the risks to the patient.
Abnormal renal function has been observed in clinical practice during the use of FASCAVIR and ritonavir, or
FOSCAVIR, ritonavir, and saquinavir.
Since FOSCAVIR decreases serum concentrations of ionized calcium, concurrent treatment with other drugs known to
influence serum calcium concentrations should be used with particular caution.
Ganciclovir The pharmacokinetics of foscarnet and ganciclovir were not altered in 13 patients receiving
either concomitant therapy or daily alternating therapy for maintenance of CMV disease.