Foscarnet (Foscavir ®) is a viral DNA polymerase inhibitor with a mechanism of action distinctly different from other antiviral drugs. It was FDA-approved in 1991 and is used as a second-line treatment for many herpesvirus infections including CMV retinitis in patients living with HIV.
Foscarnet is a pyrophosphate analogue which directly inhibits the DNA polymerase of herpesviruses by binding to the pyrophosphate binding site. This blocks the cleavage of deoxynucleotide triphosphates which prevents chain elongation. Foscarnet is active against herpesviruses at concentrations which do not affect human cellular DNA polymerases. Resistances occur due to mutations affecting the DNA polymerase pyrophosphate binding site.
Half-life is about 3h, however, as foscarnet is deposited in the bone, terminal elimination is prolonged. It does not undergo relevant hepatic metabolism. Forscarnet is excreted via the urine.
Foscarnet drug therapy may cause a wide range of adverse effects. Gastrointestinal symptoms, CNS effects, electrolyte disturbances and acute kidney injury are among the more common undesirable effects.