Foscarnet is principally used for the treatment of ganciclovir-resistant cytomegalovirus (CMV) infections in patients with the acquired immunodeficiency syndrome (AIDS) or in transplant recipients.
The mechanisms of action, pharmacokinetics, and adverse effects will be reviewed here. Treatment of the specific clinical syndromes can be found on the appropriate topic reviews.
MECHANISM OF ACTION
Foscarnet (trisodium phosphonoformate) is a pyrophosphate analog. It binds reversibly near the pyrophosphate-binding site of DNA polymerase (or reverse transcriptase) without requiring further modification . After binding, the drug blocks the cleavage of the pyrophosphate moiety from deoxynucleotide triphosphates, in turn halting DNA chain elongation. Foscarnet selectively inhibits viral polymerase; inhibition of mammalian DNA polymerase requires a 100-fold greater concentration of foscarnet than that required to block cytomegalovirus (CMV) replication .
SPECTRUM OF ACTIVITY
Foscarnet inhibits the replication, at least in vitro, of multiple herpes family viruses, hepatitis B virus, and the human immunodeficiency virus (HIV) . Clinically, foscarnet is employed almost exclusively to treat infections with cytomegalovirus (CMV), particularly when ganciclovir cannot be used, and acyclovir-resistant herpes simplex virus (HSV) and varicella zoster virus (VZV). Foscarnet is not used as an antiretroviral agent to treat HIV.
Genotypic testing can identify mutations that help predict the activity of foscarnet. This can be used to guide antiviral therapy, especially in patients who have failed their initial regimen.