Ganciclovir

From IDWiki

Background

Mechanism of Action

  • Analog of deoxyguanosine, competes with deoxyguanosine to inhibit viral DNA polymerase

Mechanisms of Resistance

  • Resistance in CMV
    • Most often conferred by mutations of UL97 kinase, which is required in order to phosphorylate ganciclovir into its active form
    • Can also develop through mutations in the target UL54 DNA polymerase

Spectrum of Activity

Pharmacokinetics and Pharmacodynamics

  • Oral bioavailability 6-8%
  • CNS penetration 24-67% of serum levels

Dosing

  • If non-obese (BMI <30), use total body weight; if obese (BMI ≥30), use adjusted body weight

Adult Dosing

  • Induction dose: 5 mg/kg q12h
  • Maintenance dose: 5 mg/kg q24h or 6 mg/kg 5x/week

Pediatric Dosing

  • Ganciclovir 5-6 mg/kg IV q12h

Safety

  • Major toxicity is cytopenias
    • Usually develops in first one to two weeks of treatment
    • Contraindicated when neutrophils <0.5 cells/mL or platelets <25 cells/mL

Drug-Drug Interactions