Valganciclovir Hydrochloride

1 INDICATIONS AND USAGE Valganciclovir is a deoxynucleoside analogue cytomegalovirus (CMV) DNA polymerase inhibitor indicated for: Adult Patients ( 1.1 ) Treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS). Prevention of CMV disease in kidney, heart, and kidney-pancreas transplant patients at high risk. Pediatric Patients ( 1.2 ) Prevention of CMV disease in kidney and heart transplant patients at high risk. 1.1 Adult Patients Treatment of Cytomegalovirus (CMV) Retinitis : Valganciclovir for oral solution is indicated for the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS) [ see Clinical Studies (14.1) ] .

6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the labeling: Hematologic Toxicity [ see Warnings and Precautions (5.1 )]. Acute Renal Failure [ see Warnings and Precautions (5.2 )] . Impairment of Fertility [ see Warnings and Precautions (5.3 )]. Fetal Toxicity [ see Warnings and Precautions (5.4 )]. Mutagenesis and Carcinogenesis [ see Warnings and Precautions (5.5) ]. The most common adverse reactions and laboratory abnormalities reported in at least one indication by greater than or equal to 20% of adult patients treated with valganciclovir tablets are diarrhea, pyrexia, fatigue, nausea, tremor, neutropenia, anemia, leukopenia, thrombocytopenia, headache, insomnia, urinary tract infection, and vomiting.

8.1 Pregnancy Risk Summary After oral administration, valganciclovir (prodrug) is converted to ganciclovir (active drug) and, therefore, Valganciclovir is expected to have reproductive toxicity effects similar to ganciclovir. In animal studies, ganciclovir caused maternal and fetal toxicity and embryo-fetal mortality in pregnant mice and rabbits as well as teratogenicity in rabbits at exposures two-times the human exposure. There are no available human data on use of valganciclovir or ganciclovir in pregnant women to establish the presence or absence of drug-associated risk.

WARNING: HEMATOLOGIC TOXICITY, IMPAIRMENT OF FERTILITY, FETAL TOXICITY, MUTAGENESIS AND CARCINOGENESIS WARNING: HEMATOLOGIC TOXICITY, IMPAIRMENT OF FERTILITY, FETAL TOXICITY, MUTAGENESIS AND CARCINOGENESIS Hematologic Toxicity: Severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, and bone marrow failure including aplastic anemia have been reported in patients treated with valganciclovir [ see Warnings and Precautions (5.1) ]. 5 WARNINGS AND PRECAUTIONS Acute renal failure: Acute renal failure may occur in elderly patients (with or without reduced renal function), patients who receive concomitant nephrotoxic drugs, or inadequately hydrated patients. Use with caution in elderly patients or those taking nephrotoxic drugs, reduce dosage in patients with renal impairment, and monitor renal function. ( 2.5 , 5.2 , 8.5 , 8.6 ) 5.1 Hematologic Toxicity Severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, and bone marrow failure including aplastic anemia have been reported in patients treated with valganciclovir or ganciclovir. Valganciclovir should be avoided if the absolute neutrophil count is less than 500 cells/µL, the platelet count is less than 25,000/µL, or the hemoglobin is less than 8 g/dL. 4 CONTRAINDICATIONS Valganciclovir is contraindicated in patients who have had a demonstrated clinically significant hypersensitivity reaction (e.g., anaphylaxis) to valganciclovir, ganciclovir, or any component of the formulation [ see Adverse Reactions (6.1) ]. Hypersensitivity to valganciclovir or ganciclovir. ( 4 )