r the first year and periodically thereafter during treatment with ZEJULA. Closely monitor patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. Medically manage hypertension with antihypertensive medications and adjustment of the ZEJULA dose, if necessary [see DOSAGE AND ADMINISTRATION (2.2) and NONCLINICAL TOXICOLOGY (13.2)].
5.4 Embryo-Fetal Toxicity
Based on its mechanism of action, ZEJULA can cause fetal harm when administered to a pregnant woman [see CLINICAL PHARMACOLOGY (12.1)]. ZEJULA has the potential to cause teratogenicity and/or embryo-fetal death since niraparib is genotoxic and targets actively dividing cells in animals and patients (e.g., bone marrow) [see WARNINGS AND PRECAUTIONS (5.2) and NONCLINICAL TOXICOLOGY (13.1)]. Due to the potential risk to a fetus based on its mechanism of action, animal developmental and reproductive toxicology studies were not conducted with niraparib.
Apprise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for 6 months after the last dose of ZEJULA [see USE IN SPECIFIC POPULATIONS (8.1, 8.3)].
6 ADVERSE REACTIONS
The following clinically significant adverse reactions are described elsewhere in the labeling:
Myelodysplastic Syndrome/Acute Myeloid Leukemia [see WARNINGS AND PRECAUTIONS (5.1)]
Bone Marrow Suppression [see WARNINGS AND PRECAUTIONS (5.2)]
Cardiovascular Effects [see WARNINGS AND PRECAUTIONS (5.3)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety of ZEJULA monotherapy 300 mg once daily has been studied in 367 patients with platinum-sensitive recurrent ovarian, fallopian tube, and primary peritoneal cancer in Trial 1 (NOVA). Adverse reactions in Trial 1 led to dose reduction or interruption in 69% of patients, most frequently from thrombocytopenia (41%) and anemia (20%). The permanent discontinuation rate due to adverse reactions in Trial 1 was 15%. The median exposure to ZEJULA in these patients was 250 days.
Table 4 and Table 5 summarize the common adverse reactions and abnormal laboratory findings, respectively, observed in patients treated with ZEJULA.
Table 4 Adverse Reactions Reported in ≥10% of Patients Receiving ZEJULA
Grades 1-4* Grades 3-4*
ZEJULA
N=367
% Placebo
N=179
% ZEJULA
N=367
% Placebo
N=179
%
* CTCAE=Common Terminology Criteria for Adverse Events version 4.02
Blood and lymphatic system disorders
Thrombocytopenia 61 5 29 0.6
Anemia 50 7 25 0
Neutropenia 30 6 20 2
Leukopenia 17 8 5 0
Cardiac Disorders
Palpitations 10 2 0 0
Gastrointestinal Disorders
Nausea 74 35 3 1
Constipation 40 20 0.8 2
Vomiting 34 16 2 0.6
Abdominal pain/distention 33 39 2 2
Mucositis/stomatitis 20 6 0.5 0
Diarrhea 20 21 0.3 1
Dyspepsia |
