Niraparib is an orally available poly (ADP-ribose) polymerase (PARP) inhibitor. The chemical name for niraparib tosylate monohydrate is 2-{4-[(3S)-piperidin-3-yl]phenyl}- 2H -indazole 7-carboxamide 4-methylbenzenesulfonate hydrate (1:1:1). The molecular formula is C 26 H 30 N 4 O 5 S and it has a molecular weight of 510.61 amu. The molecular structure is shown below: Niraparib tosylate monohydrate is a white to off-white, non-hygroscopic crystalline solid. Niraparib solubility is pH independent below the pKa of 9.95, with an aqueous free base solubility of 0.7 mg/mL to 1.1 mg/mL across the physiological pH range. Each ZEJULA tablet contains 159.3 mg, 318.7 mg, or 478.0 mg of niraparib tosylate monohydrate equivalent to 100 mg, 200 mg, or 300 mg, respectively, of niraparib free base as the active ingredient. The inactive ingredients in the core tablet are crospovidone, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone, and silicon dioxide. The film-coating consists of Opadry II Gray (100 mg), Opadry II Blue (200 mg), or Opadry II Green (300 mg). Niraparib tosylate monohydrate chemical structure

ZEJULA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated: • for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD)-positive status defined by either: o a deleterious or suspected deleterious BRCA mutation, and/or o genomic instability. Select patients for therapy based on an FDA‑authorized companion diagnostic for ZEJULA. • for the maintenance treatment of adult patients with deleterious or suspected deleterious germline BRCA -mutated recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. Select patients for therapy based on an FDA‑authorized companion diagnostic for ZEJULA

First-Line Maintenance Treatment of HRD-Positive Advanced Ovarian Cancer ZEJULA is indicated for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD)-positive status defined by either: • a deleterious or suspected deleterious BRCA mutation, and/or • genomic instability. Select patients for therapy based on an FDA ‑ authorized companion diagnostic for ZEJULA

Maintenance Treatment of Recurrent Germline BRCA -Mutated Ovarian Cancer ZEJULA is indicated for the maintenance treatment of adult patients with deleterious or suspected deleterious germline BRCA -mutated (g BRCA mut) recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. Select patients for therapy based on an FDA‑authorized companion diagnostic for ZEJULA .

• Tablets: 100-mg gray, oval-shaped, film-coated tablet debossed with “100” on one side and “Zejula” on the other side. • Tablets: 200-mg blue, oval-shaped, film-coated tablet debossed with “200” on one side and “Zejula” on the other side. • Tablets: 300-mg green, oval-shaped, film-coated tablet debossed with “300” on one side and “Zejula” on the other side. Tablets: 100 mg, 200 mg, 300 mg.

• First ‑ Line Maintenance Treatment of HRD ‑ Positive Advanced Ovarian Cancer: o For patients weighing <77 kg (<170 lbs) OR with a platelet count <150,000/mcL, the recommended dosage is 200 mg taken orally once daily. o For patients weighing ≥77 kg (≥170 lbs) AND a platelet count ≥150,000/mcL, the recommended dosage is 300 mg taken orally once daily. • Maintenance Treatment of Recurrent Germline BRCA ‑ Mutated Ovarian Cancer: The recommended dosage is 300 mg taken orally once daily. • Continue treatment until disease progression or unacceptable toxicity. • ZEJULA may be taken with or without food. • For adverse reactions, consider interruption of treatment, dose reduction, or dose discontinuation. • For patients with moderate hepatic impairment, recommended dosage is 200 mg taken orally once daily

Patient Selection First-Line Maintenance Treatment of HRD-Positive Advanced Ovarian Cancer Select patients for first-line maintenance treatment of advanced ovarian cancer with ZEJULA based on the presence of HRD defined by either a deleterious or suspected deleterious BRCA mutation, and/or genomic instability . Information on FDA ‑ authorized tests for the detection of HRD ‑ positive status for this indication is available at https://www.fda.gov/companiondiagnostics. Maintenance Treatment of Recurrent Germline BRCA -Mutated Ovarian Cancer Select patients for the maintenance treatment of recurrent ovarian cancer with ZEJULA based on the presence of deleterious or suspected deleterious germline BRCA mutations . Information on FDA‑authorized tests for the detection of deleterious or suspected deleterious germline BRCA mutations for this indication is available at https://www.fda.gov/companiondiagnostics

Recommended Dosage and Administration Continue treatment with ZEJULA until disease progression or unacceptable toxicity. Instruct patients to take their dose of ZEJULA at approximately the same time each day. Advise patients to swallow tablets whole and not to chew, crush, or split ZEJULA prior to swallowing. ZEJULA may be taken with or without food. Bedtime administration may be a potential method for managing nausea. In the case of a missed dose of ZEJULA, instruct patients to take their next dose at its regularly scheduled time. If a patient vomits or misses a dose of ZEJULA, an additional dose should not be taken. First-Line Maintenance Treatment of HRD-Positive Advanced Ovarian Cancer • For patients weighing <77 kg (<170 lbs) OR with a platelet count of <150,000/mcL, the recommended dosage is 200 mg taken orally once daily. • For patients weighing ≥77 kg (≥170 lbs) AND who have a platelet count ≥150,000/mcL, the recommended dosage is 300 mg taken orally once daily. For the maintenance treatment of advanced ovarian cancer, start ZEJULA no later than 12 weeks after their most recent platinum-containing regimen. Maintenance Treatment of Recurrent Germline BRCA -Mutated Ovarian Cancer The recommended dosage of ZEJULA is 300 mg taken orally once daily. For the maintenance treatment of recurrent ovarian cancer, start ZEJULA no later than 8 weeks after their most recent platinum-containing regimen

Dosage Modifications for Adverse Reactions To manage adverse reactions, consider interruption of treatment, dose reduction, or dose discontinuation. The recommended dosage modifications for adverse reactions are listed in Tables 1 , 2 , and 3 . Table 1. Recommended Dosage Modifications for Adverse Reactions a If further dose reduction below 100 mg/day is required, discontinue ZEJULA. Starting Dose Level 200 mg 300 mg First dose reduction 100 mg/day a 200 mg/day Second dose reduction Discontinue ZEJULA. 100 mg/day a Table 2. Dosage Modifications for Non-Hematologic Adverse Reactions CTCAE = Common Terminology Criteria for Adverse Events. Non-hematologic CTCAE ≥Grade 3 adverse reaction that persists despite medical management • Withhold ZEJULA for a maximum of 28 days or until resolution of adverse reaction. • Resume ZEJULA at a reduced dose per Table 1 . CTCAE ≥Grade 3 treatment-related adverse reaction lasting more than 28 days while patient is administered ZEJULA 100 mg/day Discontinue ZEJULA. Table 3. Dosage Modifications for Hematologic Adverse Reactions a If myelodysplastic syndrome or acute myeloid leukemia (MDS/AML) is confirmed, discontinue ZEJULA . Monitor complete blood counts weekly for the first month, monthly for the next 11 months of treatment, and periodically after this time . Platelet count <100,000/mcL First occurrence: • Withhold ZEJULA for a maximum of 28 days and monitor blood counts weekly until platelet counts return to ≥100,000/mcL. • Resume ZEJULA at same or reduced dose per Table 1 . • If platelet count is <75,000/mcL, resume at a reduced dose. Second occurrence: • Withhold ZEJULA for a maximum of 28 days and monitor blood counts weekly until platelet counts return to ≥100,000/mcL. • Resume ZEJULA at a reduced dose per Table 1 . • Discontinue ZEJULA if the platelet count has not returned to acceptable levels within 28 days of the dose interruption period or if the patient has already undergone dose reduction to 100 mg once daily. a Neutrophil <1,000/mcL or hemoglobin <8 g/dL • Withhold ZEJULA for a maximum of 28 days and monitor blood counts weekly until neutrophil counts return to ≥1,500/mcL or hemoglobin returns to ≥9 g/dL. • Resume ZEJULA at a reduced dose per Table 1 . • Discontinue ZEJULA if neutrophils and/or hemoglobin have not returned to acceptable levels within 28 days of the dose interruption period or if the patient has already undergone dose reduction to 100 mg once daily. a Hematologic adverse reaction requiring transfusion • For patients with platelet count ≤10,000/mcL, platelet transfusion should be considered. If there are other risk factors such as coadministration of anticoagulation or antiplatelet drugs, consider interrupting these drugs and/or transfusion at a higher platelet count. • Resume ZEJULA at a reduced dose per Table 1

Dosage Modifications for Hepatic Impairment For patients with moderate hepatic impairment (total bilirubin ≥1.5 to 3 x ULN and any AST level), the recommended dosage of ZEJULA is 200 mg once daily, regardless of body weight or platelet count . Monitor patients for hematologic toxicity and reduce the dose, if needed .

• Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): MDS/AML occurred in patients exposed to ZEJULA, and some cases were fatal. Monitor patients for hematological toxicity and discontinue if MDS/AML is confirmed. • Bone Marrow Suppression: Test complete blood counts weekly for the first month, monthly for the next 11 months, and periodically thereafter for clinically significant changes. • Hypertension and Cardiovascular Effects: Monitor blood pressure and heart rate at least weekly for the first 2 months, then monthly for the first year and periodically thereafter during treatment with ZEJULA. Manage with antihypertensive medications and adjustment of the dose of ZEJULA, if necessary. • Posterior Reversible Encephalopathy Syndrome (PRES): PRES has occurred in patients treated with ZEJULA. Discontinue ZEJULA if PRES is confirmed. • Embryo-Fetal Toxicity: ZEJULA can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.5 , 8.1 , 8.3 ) 5.1 Myelodysplastic Syndrome/Acute Myeloid Leukemia Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), including cases with a fatal outcome, have been reported in patients who received ZEJULA. In PRIMA, of patients within the HRD-positive population, MDS/AML occurred in 8 out of 245 (3.3%) patients treated with ZEJULA and in 3 out of 125 (2.4%) patients treated with placebo with a follow-up of 6.1 years . The duration of therapy with ZEJULA in patients who developed secondary MDS/cancer-therapy–related AML varied from 5.5 months to 5 years. In NOVA, of patients within the g BRCA mut cohort, MDS/AML occurred in 10 out of 136 (7%) patients treated with ZEJULA and in 2 out of 65 (3%) patients treated with placebo . The duration of therapy with ZEJULA in patients who developed secondary MDS/cancer-therapy–related AML varied from 3.6 months to 5.9 years. All patients who developed secondary MDS/cancer-therapy–related AML had received previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy. For suspected MDS/AML or prolonged hematological toxicities, refer the patient to a hematologist for further evaluation. Discontinue ZEJULA if MDS/AML is confirmed

Bone Marrow Suppression Hematologic adverse reactions, including thrombocytopenia, anemia, neutropenia, and/or pancytopenia have been reported in patients treated with ZEJULA . In PRIMA, the overall incidences of ≥Grade 3 thrombocytopenia, anemia, and neutropenia were reported in 39%, 31%, and 21%, respectively, of patients receiving ZEJULA. Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred in 4%, 2%, and 2%, respectively, of patients. In patients who were administered a starting dose of ZEJULA based on baseline weight or platelet count, ≥Grade 3 thrombocytopenia, anemia, and neutropenia were reported in 22%, 23%, and 15%, respectively, of patients receiving ZEJULA. Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred in 3%, 3%, and 2%, respectively, of patients. In NOVA, ≥Grade 3 thrombocytopenia, anemia, and neutropenia were reported in 29%, 25%, and 20%, respectively, of patients receiving ZEJULA. Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred in 3%, 1%, and 2%, respectively, of patients. Do not start ZEJULA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete blood counts weekly for the first month, monthly for the next 11 months of treatment, and periodically after this time. If hematological toxicities do not resolve within 28 days following interruption, discontinue ZEJULA and refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics

Hypertension and Cardiovascular Effects Hypertension and hypertensive crisis have been reported in patients treated with ZEJULA . In PRIMA, Grade 3 to 4 hypertension occurred in 6% of patients treated with ZEJULA compared with 1% of placebo-treated patients with a median time from first dose to first onset of 43 days (range: 1 to 531 days) and with a median duration of 12 days (range: 1 to 61 days). There were no discontinuations due to hypertension. In NOVA, Grade 3 to 4 hypertension occurred in 9% of patients treated with ZEJULA compared with 2% of placebo-treated patients with a median time from first dose to first onset of 77 days (range: 4 to 504 days) and with a median duration of 15 days (range: 1 to 86 days). Discontinuation due to hypertension occurred in <1% of patients. Monitor blood pressure and heart rate at least weekly for the first 2 months, then monthly for 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 dose of ZEJULA, if necessary

Posterior Reversible Encephalopathy Syndrome Posterior reversible encephalopathy syndrome (PRES) occurred in 0.1% of 2,165 patients treated with ZEJULA in clinical trials and has also been described in postmarketing reports . Signs and symptoms of PRES include seizure, headache, altered mental status, visual disturbance, or cortical blindness, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably magnetic resonance imaging. Monitor all patients treated with ZEJULA for signs and symptoms of PRES. If PRES is suspected, promptly discontinue ZEJULA and administer appropriate treatment. The safety of reinitiating ZEJULA in patients previously experiencing PRES is not known

Embryo-Fetal Toxicity Based on its mechanism of action, ZEJULA can cause fetal harm when administered to a pregnant woman . 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) . 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 .