Ganciclovir

Background

• Guanosine nucleoside analogue similar to acyclovir
• Indications: CMV after hematopoietic stem cell transplantation, CMV after solid organ transplantation, Congenital CMV, Cytomegalovirus, Herpesviridae, Macacine alphaherpesvirus 1, Post-transplant acute limbic encephalitis

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

• Active against HSV-1, HSV-2, VZV, CMV, HHV-6, and HHV-8

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

• Zidovudine, didanosine, probenecid, and imipenem-cilastatin (increases risk of seizures)