n and findings in animals, VENCLEXTA may cause embryo-fetal harm when administered to a pregnant woman. In an embryo-fetal study conducted in mice, administration of venetoclax to pregnant animals at exposures equivalent to that observed in patients at the recommended dose of 400 mg daily resulted in post-implantation loss and decreased fetal weight. There are no adequate and well-controlled studies in pregnant woman using VENCLEXTA. Advise females of reproductive potential to avoid pregnancy during treatment. If VENCLEXTA is used during pregnancy or if the patient becomes pregnant while taking VENCLEXTA, the patient should be apprised of the potential hazard to the fetus [see Use in Specific Populations (8.1)].
6 ADVERSE REACTIONS
The following serious adverse events are discussed in greater detail in other sections of the labeling:
Tumor Lysis Syndrome [see Warnings and Precautions (5.1)]
Neutropenia [see Warnings and Precautions (5.2)]
Because clinical trials are conducted under widely variable conditions, adverse event rates observed in clinical trials of a drug cannot be directly compared with rates of clinical trials of another drug and may not reflect the rates observed in practice.
6.1 Clinical Trial Experience The safety of single agent VENCLEXTA at the 400 mg recommended daily dose following a dose ramp-up schedule is based on pooled data of 240 patients with previously treated CLL from two phase 2 trials and one phase 1 trial. In the pooled dataset, the median age was 66 years (range: 29 to 85 years), 95% were white, and 69% were male. The median number of prior therapies was 3 (range: 1 to 12). The median duration of treatment with VENCLEXTA at the time of data analysis was approximately 10.3 months (range: 0 to 34.1 months). Approximately 46% of patients received VENCLEXTA for more than 48 weeks.
The most common adverse reactions (≥20%) of any grade were neutropenia, diarrhea, nausea, anemia, upper respiratory tract infection, thrombocytopenia, and fatigue.
Serious adverse reactions were reported in 43.8% of patients. The most frequent serious adverse reactions (≥2%) were pneumonia, febrile neutropenia, pyrexia, autoimmune hemolytic anemia (AIHA), anemia, and TLS.
Discontinuations due to adverse reactions occurred in 8.3% of patients. The most frequent adverse reactions leading to drug discontinuation were thrombocytopenia and AIHA.
Dosage adjustments due to adverse reactions occurred in 9.6% of patients. The most frequent adverse reactions leading to dose adjustments were neutropenia, febrile neutropenia, and thrombocytopenia.
Adverse reactions reported in 3 trials of patients with previously treated CLL using single agent VENCLEXTA are presented in Table 7.
Table 7. Adverse Reactions Reported in ≥10% (Any Grade) or ≥5% (Grade 3 or 4) of Patients with CLL Body System Adverse Reaction Any Grade (%)
N=240 Grade 3 or 4 (%)
N=240
Blood and lymphatic system disorders Neutropeniaa 45 41
Anemiab 29 18
Thrombocytopeniac 22 15
Febrile neutropenia 5 5
Gastrointestinal disorders Diarrhea 35 <1
Nausea 33 <1
Vomiting 15 <1
Constipation 14 0
General disorders and
administration site conditions Fatigue 21 2
Pyrexia 16 <1
Peripheral edema 11 <1
Infections and infestations Upper respiratory tract infection 22 1
Pneumonia 8 5
Metabolic and nutrition disorders Hypokalemia 12 4
Musculoskeletal and
connective tissue disorders Back pain 10 <1
Nervous system disorders H |
