Foscarnet

crop_square Key points

  • check_circle Pyroposphate analogue directly inhibiting DNA polymerase of herpesviruses
  • check_circle Deposition in bones prolongs half-life
  • check_circle Less well tolerated than other antivirals

crop_square Background and biochemistry

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.

crop_square Mechanism of action

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.

crop_square Drugs and spectrum of activity

  • Foscarnet (Foscavir ®)

crop_square Pharmacokinetics

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.

crop_square Adverse drug effects

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.