VALCYTE- valganciclovir hydrochloride tablet, film coated
VALCYTE- valganciclovir hydrochloride powder, for solution
WARNING: HEMATOLOGIC TOXICITY, IMPAIRMENT OF FERTILITY, FETAL TOXICITY, MUTAGENESIS AND CARCINOGENESIS
Hematologic Toxicity: Severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, bone marrow aplasia and aplastic anemia have been reported in patients treated with VALCYTE [see Warnings and Precautions (5.1)].
Impairment of Fertility: Based on animal data, VALCYTE may cause temporary or permanent inhibition of spermatogenesis [see Warnings and Precautions (5.2)].
Fetal Toxicity: Based on animal data, VALCYTE has the potential to cause birth defects in humans [see Warnings and Precautions (5.3)].
Mutagenesis and Carcinogenesis: Based on animal data, VALCYTE has the potential to cause cancers in humans [see Warnings and Precautions (5.4)].
1 INDICATIONS AND USAGE
1.1 Adult Patients
Treatment of Cytomegalovirus (CMV) Retinitis: VALCYTE is indicated for the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS) [see Clinical Studies (14.1)].
Prevention of CMV Disease: VALCYTE is indicated for the prevention of CMV disease in kidney, heart, and kidney-pancreas transplant patients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-]) [see Clinical Studies (14.1)].
1.2 Pediatric Patients
? Prevention of CMV Disease: VALCYTE is indicated for the prevention of CMV disease in kidney transplant patients (4 months to 16 years of age) and heart transplant patients (1 month to 16 years of age) at high risk [see Clinical Studies (14.2)].
2 DOSAGE AND ADMINISTRATION
2.1 General Dosing Information
Adult patients should use VALCYTE tablets, not VALCYTE for oral solution.
VALCYTE for oral solution and tablets should be taken with food [see Clinical Pharmacology (12.3)].
VALCYTE for oral solution (50 mg/mL) must be prepared by the pharmacist prior to dispensing to the patient [see Dosage and Administration (2.4)].
2.2 Recommended Dosage in Adult Patients with Normal Renal Function
For dosage recommendations in adult patients with renal impairment [see Dosage and Administration (2.5)].
Treatment of CMV Retinitis:
Induction: The recommended dosage is 900 mg (two 450 mg tablets) taken orally twice a day for 21 days.
Maintenance: Following induction treatment, or in adult patients with inactive CMV retinitis, the recommended dosage is 900 mg (two 450 mg tablets) taken orally once a day.
Prevention of CMV Disease:
For adult patients who have received a heart or kidney-pancreas transplant, the recommended dosage is 900 mg (two 450 mg tablets) taken orally once a day starting within 10 days of transplantation until 100 days post-transplantation.
For adult patients who have received a kidney transplant, the recommended dosage is 900 mg (two 450 mg tablets) taken orally once a day starting within 10 days of transplantation until 200 days post-transplantation.
Mechanism of Action
Valganciclovir is an antiviral drug
Mechanism of Action: Valganciclovir is an L-valyl ester (prodrug) of ganciclovir that exists as a mixture of two diastereomers. After oral administration, both diastereomers are rapidly converted to ganciclovir by intestinal and hepatic esterases. Ganciclovir is a synthetic analogue of 2?-deoxyguanosine, which inhibits replication of human CMV in cell culture and in vivo.
In CMV-infected cells ganciclovir is initially phosphorylated to ganciclovir monophosphate by the viral protein kinase, pUL97. Further phosphorylation occurs by cellular kinases to produce ganciclovir triphosphate, which is then slowly metabolized intracellularly (half-life 18 hours). As the phosphorylation is largely dependent on the viral kinase, phosphorylation of ganciclovir occurs preferentially in virus-infected cells. The virustatic activity of ganciclovir is due to inhibition of the viral DNA polymerase, pUL54, synthesis by ganciclovir triphosphate.
HOW SUPPLIED/STORAGE AND HANDLING
VALCYTE tablets: Supplied as 450 mg, pink, convex oval tablets with "VGC" on one side and "450? on the other side. Each tablet contains valganciclovir HCl equivalent to 450 mg valganciclovir. VALCYTE is supplied in bottles of 60 tablets (NDC 0004-0038-22).
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP controlled room temperature].
VALCYTE for oral solution: Supplied as a white to slightly yellow powder blend for constitution, forming a colorless to brownish yellow tutti-frutti flavored solution. Available in glass bottles containing approximately 100 mL of solution after constitution. Each bottle can deliver up to a total of 88 mL of solution. Each bottle is supplied with a bottle adapter and 2 oral dispensers (NDC 0004-0039-09).
Prior to dispensing to the patient, VALCYTE for oral solution must be prepared by the pharmacist [see Dosage and Administration (2.4)].
Store dry powder at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP controlled room temperature].
Store constituted solution under refrigeration at 2°C to 8°C (36°F to 46°F) for no longer than 49 days. Do not freeze.