valganciclovir

Valganciclovir is an antiviral medication that acts as a prodrug of ganciclovir, designed to improve oral bioavailability compared with intravenous ganciclovir. After oral administration, valganciclovir is rapidly converted to ganciclovir in the intestinal mucosa and liver, providing systemic exposure to the active drug.

Indications include treatment of cytomegalovirus (CMV) disease in adults and in pediatric patients aged 4 weeks and older; prophylaxis of CMV disease in seropositive recipients of solid-organ transplants; and maintenance or treatment of CMV retinitis in immunocompromised individuals, including people with AIDS.

Mechanism of action: valganciclovir is a nucleoside analog that, once phosphorylated to ganciclovir triphosphate, inhibits CMV DNA polymerase, thereby inhibiting viral DNA replication. Activation occurs preferentially in CMV-infected cells via the CMV UL97 kinase, contributing to selectivity.

Administration and dosing: available as tablets and oral solution. Dosing depends on indication and renal function. Prophylaxis in solid-organ transplant recipients is commonly 900 mg once daily starting within days after transplantation, continued for about 100–200 days depending on risk. For treatment of CMV retinitis, induction therapy is typically 900 mg twice daily, followed by maintenance therapy of 900 mg once daily. Dose adjustments are required for renal impairment.

Pharmacokinetics: relatively high oral bioavailability relative to ganciclovir; main route of elimination is renal excretion of the unchanged drug and metabolites.

Adverse effects: the most important safety concern is myelosuppression, including neutropenia, anemia, and thrombocytopenia, which can require dose adjustments or interruption. Other common adverse effects include nausea, diarrhea, headache, hepatic transaminase elevations, and fever. Valganciclovir is teratogenic in animals and is contraindicated in pregnancy; lactation is discouraged.

Drug interactions: caution with other myelosuppressive agents such as zidovudine or chemotherapy, and with nephrotoxic drugs or calcineurin inhibitors; monitor CBC and renal function during therapy.

Contraindications and precautions: hypersensitivity to valganciclovir or ganciclovir; preexisting severe neutropenia; caution in pregnancy and lactation.

Resistance: CMV may develop resistance due to UL97 kinase mutations reducing drug activation or UL54 polymerase mutations. Cross-resistance with ganciclovir is possible.