VALCYTE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VALCYTE (VALCYTE).
Valganciclovir is an L-valyl ester (prodrug) of ganciclovir. After oral administration, it is rapidly hydrolyzed to ganciclovir. Ganciclovir is phosphorylated to ganciclovir triphosphate, which inhibits viral DNA synthesis by competitive inhibition of viral DNA polymerase and incorporation into viral DNA, causing chain termination.
| Metabolism | Valganciclovir is rapidly hydrolyzed to ganciclovir by esterases in the intestinal wall and liver. Ganciclovir is primarily eliminated unchanged by renal excretion via glomerular filtration and tubular secretion. Minimal metabolism via aldehyde oxidase and xanthine oxidase to 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine. |
| Excretion | Renal excretion (primarily glomerular filtration and tubular secretion). Approximately 82-90% of the administered dose is recovered unchanged in urine. Fecal excretion is minimal (<5%). Biliary excretion is negligible. |
| Half-life | Terminal elimination half-life: 3-5 hours (valganciclovir) and 3.5-4.5 hours (ganciclovir, after conversion). In patients with renal impairment, half-life is prolonged: up to 10-30 hours depending on creatinine clearance. Hemodialysis reduces half-life to approximately 4-5 hours. |
| Protein binding | Valganciclovir: approximately 1-2% bound to plasma proteins. Ganciclovir: approximately 1-2% bound to plasma proteins. Binding is negligible and not clinically significant for drug interactions. |
| Volume of Distribution | Ganciclovir: Vd = approximately 0.6-0.8 L/kg (range 0.5-1.0 L/kg). Distributes widely into body tissues, including lungs, liver, kidney, and brain. Extensive distribution is clinically relevant for treating systemic CMV infections including CNS involvement. |
| Bioavailability | Oral valganciclovir: absolute bioavailability of ganciclovir is approximately 60% (range 40-70%). Bioavailability is enhanced approximately 10-fold compared to oral ganciclovir (6-9%). After oral administration, valganciclovir is rapidly converted to ganciclovir by intestinal and hepatic esterases. |
| Onset of Action | Oral: Time to peak plasma concentration (Tmax) of ganciclovir is 2-3 hours. Clinical antiviral effect occurs within 24-48 hours. Intravenous: Ganciclovir (administered as valganciclovir prodrug) achieves effective concentrations immediately; Tmax approximately 1-2 hours. |
| Duration of Action | Oral: Dosing interval is every 12 hours; ganciclovir concentrations remain above IC50 for CMV for the entire dosing interval. Duration of clinical effect: 12 hours (sustained viral suppression with twice-daily dosing). In renal impairment, duration is extended; dosing interval adjusted accordingly. |
| Action Class | Antiviral (Non-HIV) drugs |
| Brand Substitutes | Valgaids Tablet, Vagacyte 450mg Tablet, Cmvigone 450 Tablet, Valcip Tablet, Valgacel 450mg Tablet |
For cytomegalovirus (CMV) retinitis in immunocompromised patients: 900 mg orally twice daily for 21 days, then 900 mg once daily as maintenance. For prevention of CMV in transplant recipients: 900 mg orally once daily starting within 10 days of transplant, continuing up to 100 days post-transplant.
| Dosage form | TABLET |
| Renal impairment | Based on creatinine clearance (CrCl): CrCl >=60 mL/min: no adjustment. CrCl 40-59 mL/min: 450 mg twice daily for induction, 450 mg once daily for maintenance/prevention. CrCl 25-39 mL/min: 450 mg once daily for induction, 450 mg every 48 hours for maintenance/prevention. CrCl 10-24 mL/min: 450 mg every 48 hours for induction, 450 mg twice weekly for maintenance/prevention. CrCl <10 mL/min (on hemodialysis): 450 mg twice weekly after dialysis. |
| Liver impairment | No specific dosage adjustments are recommended for hepatic impairment. However, use with caution in patients with significant hepatic impairment due to potential for increased adverse effects. No Child-Pugh based modifications have been established. |
| Pediatric use | For prevention of CMV in pediatric kidney or heart transplant recipients: 15 mg/kg (up to 900 mg) orally once daily starting within 10 days of transplant for up to 100 days. For CMV retinitis in immunocompromised pediatric patients: 15 mg/kg (up to 900 mg) orally twice daily for 21 days, then 15 mg/kg once daily (up to 900 mg) for maintenance. Dosing based on body surface area may be used: 900 mg/m² (up to 900 mg) twice daily for induction, then 900 mg/m² (up to 900 mg) once daily for maintenance/prevention. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VALCYTE (VALCYTE).
| Breastfeeding | Valganciclovir and its active metabolite ganciclovir are excreted in human milk. The milk-to-plasma (M/P) ratio for ganciclovir is approximately 0.28 based on a small study. High doses could cause infant toxicity (bone marrow suppression, hepatic impairment). Breastfeeding is generally not recommended during therapy; alternatives should be considered. |
| Teratogenic Risk | Valganciclovir (VALCYTE) is a prodrug of ganciclovir, an antiviral with animal studies showing teratogenicity at subtherapeutic doses. Human data are limited, but based on ganciclovir, it is classified as FDA Category C. First trimester: Potential for fetal harm; use only if benefit outweighs risk. Second/third trimester: Limited data; risk of fetal toxicity with maternal high doses. Embryofetal toxicity includes growth restriction, congenital anomalies (cleft palate, anophthalmia, etc.) in animals. |
■ FDA Black Box Warning
Hematologic toxicity: Ganciclovir, the active metabolite, is associated with severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, and bone marrow suppression, including aplastic anemia. Impairment of fertility: Based on animal data, valganciclovir may cause temporary or permanent inhibition of spermatogenesis in males and suppression of fertility in females. Fetal toxicity: Based on animal data, valganciclovir has the potential to cause birth defects. Carcinogenicity: Based on animal data, valganciclovir is considered a potential carcinogen. Mutagenicity: Based on animal data, valganciclovir is considered a potential mutagen.
| 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"]
| Precautions | ["Hematologic toxicity: Monitor CBC and platelet counts; use with caution in patients with pre-existing cytopenias","Renal impairment: Dose adjustment required based on creatinine clearance; increased risk of toxicity in renal impairment","Teratogenicity: Advise females of reproductive potential to use effective contraception during and for 30 days after treatment; advise males to use barrier contraception during and for 90 days after treatment","Impaired fertility: May cause temporary or permanent inhibition of spermatogenesis and suppression of fertility","Carcinogenicity and mutagenicity: Consider as potential carcinogen and mutagen","Overdose: Hemodialysis may be useful for reducing serum concentrations"] |
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| Geriatric use | No specific dosage adjustments are recommended solely for age. However, renal function should be assessed and dose adjusted accordingly as elderly patients are more likely to have decreased renal function. Use the lowest effective dose and monitor closely for adverse effects. |
| Fetal Monitoring | Maternal: Complete blood count (CBC) with differential and platelets weekly during induction, then every 2 weeks; serum creatinine at baseline and periodically; liver function tests. Fetal: Routine prenatal care; consider growth scans if prolonged therapy. Monitor for maternal anemia, neutropenia, thrombocytopenia, and renal impairment. |
| Fertility Effects | Valganciclovir/ganciclovir cause reproductive toxicity in animals with reduced fertility and testicular degeneration. Human data: Reversible inhibition of spermatogenesis and reduced sperm counts have been reported. Effects on female fertility are uncertain; consider impact on reproductive potential, especially in males. |