VALGANCICLOVIR HYDROCHLORIDE
Clinical safety rating: avoid
Contraindicated (not allowed)
Valganciclovir is an L-valyl ester prodrug of ganciclovir. After oral administration, it is rapidly hydrolyzed to ganciclovir, which is a synthetic guanosine analog. Ganciclovir is phosphorylated to ganciclovir triphosphate, which competitively inhibits viral DNA polymerase and incorporates into viral DNA, causing termination of viral DNA elongation.
| Metabolism | Valganciclovir is rapidly and extensively hydrolyzed to ganciclovir by intestinal and hepatic esterases. No other metabolites have been identified. Ganciclovir is minimally metabolized; it is eliminated primarily by glomerular filtration and active tubular secretion. |
| Excretion | Primarily renal excretion of unchanged drug (approximately 90%), with the remainder as ganciclovir. Biliary/fecal elimination accounts for <5%. |
| Half-life | Terminal elimination half-life of ganciclovir after valganciclovir administration is approximately 4-5 hours in patients with normal renal function. In renal impairment, half-life is significantly prolonged, up to 30-40 hours in severe impairment (CrCl <10 mL/min). |
| Protein binding | 1-2% bound to plasma proteins (negligible binding for ganciclovir). |
| Volume of Distribution | Apparent Vd of ganciclovir is approximately 0.74 L/kg, indicating distribution into total body water. Extensive penetration into tissues including retina, brain, and CSF. |
| Bioavailability | Oral bioavailability of valganciclovir (converted to ganciclovir) is approximately 60% when taken with food. Bioavailability is negligible for the IV route (not applicable); valganciclovir is only oral. |
| Onset of Action | Conversion to ganciclovir occurs rapidly; peak ganciclovir concentrations are achieved within 1-3 hours after oral valganciclovir. Antiviral effect begins within hours, but clinical response in CMV retinitis may take weeks. |
| Duration of Action | Dosing interval is typically every 12 hours for induction and once daily for maintenance in patients with normal renal function. The duration of action is determined by the pharmacokinetics of ganciclovir; trough levels remain above IC50 for CMV throughout the dosing interval. |
Oral: 900 mg twice daily for cytomegalovirus (CMV) retinitis induction in immunocompromised patients; for prevention in transplant recipients: 900 mg once daily starting within 10 days of transplant.
| Dosage form | TABLET |
| Renal impairment | CrCl (mL/min): 40-59: 450 mg twice daily; 25-39: 450 mg once daily; 10-24: 450 mg every 48 hours; <10: not recommended (use ganciclovir IV). |
| Liver impairment | No specific Child-Pugh based adjustments required; pharmacokinetics not significantly altered in hepatic impairment. |
| Pediatric use | Weight-based: 15-20 mg/kg twice daily for CMV retinitis; for prevention: data limited, typically same dose based on weight up to adult dose. |
| Geriatric use | Initiate at lower end of dosing range due to age-related renal function decline; adjust per renal function; monitor for hematologic and renal toxicity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Probenecid may decrease ganciclovir excretion Can cause severe myelosuppression and mutagenesis.
| Breastfeeding | No human studies; valganciclovir is excreted in rat milk. M/P ratio unknown. Due to potential for serious adverse effects (e.g., carcinogenicity, hematotoxicity), breastfeeding is not recommended during therapy. |
| Teratogenic Risk | FDA Pregnancy Category D. First trimester: valganciclovir is teratogenic in animal studies; human data insufficient but associated with fetal malformations. Second/third trimester: may cause fetal toxicity including growth restriction, microcephaly, and hematologic effects. Contraindicated unless benefit outweighs risk. |
■ FDA Black Box Warning
Valganciclovir is indicated for the treatment of CMV retinitis in patients with AIDS and for the prevention of CMV disease in high-risk transplant recipients. It is associated with hematologic toxicity, including neutropenia, anemia, thrombocytopenia, and pancytopenia. It is also mutagenic, carcinogenic, and teratogenic. It may cause significant impairment of fertility.
| Common Effects | Diarrhea Fever Vomiting Anemia low number of red blood cells Decreased white blood cell count Low blood platelets Insomnia difficulty in sleeping Tremors |
| Serious Effects |
["Hypersensitivity to valganciclovir, ganciclovir, or any component of the formulation","Absolute neutrophil count <500 cells/μL","Platelet count <25,000/μL","Hemoglobin <8 g/dL","Concurrent use with didanosine (increased risk of pancreatitis)"]
| Precautions | ["Hematologic toxicity: neutropenia, anemia, thrombocytopenia, pancytopenia; monitor blood counts","Impaired renal function: dose adjustment required based on creatinine clearance","Mutagenic, carcinogenic, and teratogenic potential","Impairment of fertility in males and females","Fetal toxicity; avoid pregnancy during treatment","Acute renal failure in elderly patients or those with pre-existing renal impairment","Seizures and other neurological adverse events"] |
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| Fetal Monitoring |
| Monitor maternal CBC with differential, renal function, liver enzymes at baseline and regularly. For pregnant women exposed: fetal ultrasound for growth and anatomy; consider amniotic fluid assessment due to risk of oligohydramnios. Neonatal monitoring for neutropenia, thrombocytopenia, and auditory/visual function. |
| Fertility Effects | Animal studies: valganciclovir causes reduced fertility and spermatogenesis in males; human data lacking. Female fertility may be impaired based on animal findings; no adequate human studies. Advise reproductive-age patients of potential effects on fertility. |