BLACK BOX WARNING
- severe neutropenia, anemia, and thrombocytopenia
- teratogenicity and carcinogenicity — handle as cytotoxic
valganciclovir
Brand: Valcyte
⚠ BBW Prototype: ganciclovir
Drug Class: antiviral — ganciclovir prodrug
Drug Family: antiviral
Subclass: oral prodrug of ganciclovir
Organ Systems: infectious-disease
Mechanism of Action
L-valyl ester prodrug of ganciclovir; rapidly hydrolyzed to ganciclovir after absorption, achieving ~60% oral bioavailability (vs. ~6–9% for oral ganciclovir); then activated by viral UL97 kinase and cellular kinases to ganciclovir triphosphate.
CMV UL97 kinaseviral DNA polymerase
Indications
- CMV retinitis treatment in AIDS (induction and maintenance)
- CMV disease prevention in solid organ transplant recipients
- CMV disease prevention in pediatric kidney and heart transplant recipients
Contraindications
- ganciclovir/valganciclovir hypersensitivity
- hemodialysis patients (contraindicated; excessive drug accumulation)
Adverse Effects
Common
- neutropenia
- anemia
- thrombocytopenia
- diarrhea
- nausea
Serious
- severe myelosuppression (dose-limiting)
- nephrotoxicity
- carcinogenesis/mutagenesis (animal data)
- impaired fertility
Pharmacokinetics (ADME)
| Absorption | 59–61% bioavailability after oral administration with food (food increases AUC ~30%) |
| Distribution | widely distributed (same as ganciclovir after conversion) |
| Metabolism | rapidly hydrolyzed to ganciclovir by intestinal and hepatic esterases |
| Excretion | renal (as ganciclovir, >90% unchanged) |
| Half-life | 4 hours (as ganciclovir after conversion) |
| Onset | rapid |
| Peak | 1–3 hours |
| Duration | 12 hours |
| Protein Binding | 1–2% |
| Vd | large (same as ganciclovir) |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| zidovudine/myelosuppressive drugs | additive bone marrow suppression | major |
| mycophenolate mofetil | competition for renal tubular secretion; elevated levels of both drugs | moderate |
| didanosine | increased didanosine AUC when combined; increase toxicity risk | moderate |
Nursing Considerations
- Administer with food to maximize absorption; instruct patients not to crush or break tablets (cytotoxic — handle with care).
- Perform CBC with differential weekly during CMV treatment and twice monthly for prophylaxis; neutropenia is the primary reason for dose modification.
- NEVER administer to patients on hemodialysis — use IV ganciclovir with dose adjusted for dialysis instead.
- Warn patients about teratogenicity; effective contraception required during and for 30–90 days after therapy for both men and women.
Clinical Pearls
- Valganciclovir has essentially replaced IV ganciclovir for CMV disease prophylaxis in transplant recipients and maintenance therapy for CMV retinitis because its oral bioavailability achieves equivalent ganciclovir AUC to IV administration.
- The dose of valganciclovir for CMV prophylaxis (900 mg once daily) differs from the treatment dose (900 mg twice daily); nurses must verify the indication-specific dosing regimen.
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.