Foscarnet

185

Summary

Foscarnet is an antiviral that inhibits viral DNA polymerase, viral RNA polymerase, and reverse transcriptase. Remember that since foscarnet is not phosphorylated by viral kinases, it is not susceptible to the same resistance mechanisms as acyclovir and ganciclovir. For this reason, it is often used in the second-line setting to treat strains of HSV and CMV that have mutated their viral kinases. Know that foscarnet is associated with nephrotoxicity, hypocalcemia, and seizures.

Key Points

  • Foscarnet
    • Mechanism
      • Pyrophosphate analog:
        • Viral DNA polymerase inhibitor
          • Also inhibits viral RNA polymerase
        • HIV reverse transcriptase inhibitor
      • Does not require phosphorylation by viral or cellular kinases
        • Can treat viral strains with mutated or downregulated viral kinase
    • Clinical Use
      • HSV
        • Especially in immunocompromised patients with kinase-mutated viral strains resistant to treatment by acyclovir
        • Cidofovir may also be used in this setting
      • CMV
        • Especially in immunocompromised patients with CMV retinitis and colitis with kinase-mutated viral strains resistant to treatment by ganciclovir
        • Cidofovir may also be used in this setting
    • Adverse Effects
      • Nephrotoxicity
        • Seen in ~27% of patients
        • Directly toxic to renal tubular cells
      • Hypocalcemia
        • Hypomagnesemia and hypokalemia are less characteristic and may also be seen
      • Seizures
        • Rare side effect; may be secondary to electrolyte abnormalities
      • Genital ulcerations, anemia, and GI upset may also be seen
    • Resistance
      • Mutated DNA polymerase