BLACK BOX WARNING
- neutropenia, anemia, thrombocytopenia (may require treatment modification)
- carcinogenesis and mutagenesis (animal data)
- impaired fertility
ganciclovir
Brand: Cytovene
⚠ BBW Prototype Drug
Drug Class: antiviral — guanosine analog
Drug Family: antiviral
Subclass: anti-CMV nucleoside analog
Organ Systems: infectious-disease
Mechanism of Action
Phosphorylated by CMV-encoded UL97 kinase to the monophosphate form; then by cellular kinases to ganciclovir triphosphate, which inhibits CMV DNA polymerase 10 times more potently than cellular DNA polymerases; also competitively inhibits dGTP incorporation.
CMV UL97 kinase (phosphorylation)viral DNA polymerase
Indications
- CMV retinitis in AIDS patients
- CMV disease prophylaxis in transplant recipients (usually as IV bridge before switching to oral valganciclovir)
- CMV esophagitis/colitis
Contraindications
- ganciclovir/valganciclovir hypersensitivity
- severe neutropenia (ANC <500/mm3) — relative
- severe thrombocytopenia (relative)
Adverse Effects
Common
- neutropenia (dose-limiting)
- thrombocytopenia
- anemia
- fever
Serious
- severe myelosuppression
- nephrotoxicity
- CNS effects (confusion, seizures)
- carcinogenesis (animal data)
- spermatogenesis impairment
Pharmacokinetics (ADME)
| Absorption | IV (poor oral bioavailability ~6–9% for IV; largely replaced by valganciclovir orally) |
| Distribution | widely distributed; CSF penetration ~24–70% of plasma |
| Metabolism | phosphorylated intracellularly; not metabolized further in plasma |
| Excretion | renal (91–99% unchanged); dose-critical adjustment in renal impairment |
| Half-life | 3.5–4.8 hours |
| Onset | immediate (IV) |
| Peak | end of infusion |
| Duration | 12 hours |
| Protein Binding | 1–2% |
| Vd | moderate-large |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| zidovudine | additive myelosuppression; avoid combination or monitor CBC intensively | major |
| imipenem-cilastatin | additive seizure risk in renal failure | major |
| mycophenolate mofetil | competition for renal tubular secretion; both drug levels may increase | moderate |
| probenecid | reduces renal tubular secretion of ganciclovir; increased exposure | moderate |
Nursing Considerations
- Monitor CBC with differential twice weekly during induction and weekly during maintenance; neutropenia is the primary dose-limiting toxicity — colony-stimulating factors (filgrastim, sargramostim) may be required.
- Administer IV infusion over at least 1 hour (not as rapid infusion); ensure adequate hydration throughout infusion.
- Handle ganciclovir as a cytotoxic agent; women of childbearing age and pregnant nurses should not prepare doses. Male patients should use effective contraception during and for 90 days after therapy.
- Renal dose adjustment is mandatory; monitor SCr at least twice weekly — dose or frequency adjustments required at all levels of renal impairment.
Clinical Pearls
- Ganciclovir IV is largely reserved for hospitalized patients with severe CMV disease or initial induction therapy; oral valganciclovir (ganciclovir prodrug with 60% bioavailability) has replaced IV ganciclovir for most outpatient maintenance and prophylaxis indications.
- CMV resistance via UL97 kinase mutations reduces ganciclovir phosphorylation; foscarnet (which does not require viral phosphorylation) is the primary alternative for ganciclovir-resistant CMV.
Safety Profile
Pregnancy contraindicated
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.