Ganciclovir

Summary

Ganciclovir is a guanosine analog used in the treatment of cytomegalovirus or CMV. Ganciclovir functions by inhibiting viral DNA polymerase in infected cells, which prevents viral replication. To ensure its specificity to infected cells, ganciclovir is activated by the addition of a phosphate group by a viral kinase expressed by CMV. Resistance to ganciclovir usually occurs via mutation of this needed viral kinase. The most important side effects of ganciclovir include bone marrow suppression and kidney toxicity.

Key Points

• Ganciclovir
  • Valganciclovir is a prodrug of ganciclovir with better oral bioavailability
  • Mechanism
    • Guanosine analog inhibits DNA polymerase
      • Causes DNA chain termination, preventing viral DNA replication
        • Similar chemical structure to acyclovir
      • Requires phosphorylation by CMV kinase
        • Phosphorylation produces an active triphosphate form
  • Clinical Use
    • CMV
      • Usually first-line in treatment of all patients with CMV
  • Adverse Effects
    • Bone marrow suppression
      • Leukopenia, neutropenia, thrombocytopenia
      • Can be countered with hematopoietic growth factors (e.g. G-CSF)
    • Nephrotoxicity
      • Rare side effect seen in few patients
      • Mechanism is unknown
    • More toxic to host enzymes than acyclovir
  • Resistance
    • Mutated CMV viral kinase