ZEJULA

Indications and Usage ( 1.1 ) 3/2026 Dosage and Administration ( 2.1 ) 3/2026

1 INDICATIONS AND USAGE 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. ( 1.1 , 2.1 ) • 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. ( 1.2 , 2.1 ) 1.1 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 [see Dosage and Administration ( 2.1 )] . 1.2 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 [see Dosage and Administration ( 2.1 )] .

2 DOSAGE AND ADMINISTRATION • 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. ( 2.2 ) 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. ( 2.2 ) • Maintenance Treatment of Recurrent Germline BRCA ‐ Mutated Ovarian Cancer: The recommended dosage is 300 mg taken orally once daily. ( 2.2 ) • Continue treatment until disease progression or unacceptable toxicity. ( 2.2 ) • ZEJULA may be taken with or without food. ( 2.2 ) • For adverse reactions, consider interruption of treatment, dose reduction, or dose discontinuation. ( 2.3 ) • For patients with moderate hepatic impairment, recommended dosage is 200 mg taken orally once daily. ( 2.4 ) 2.1 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 [see Clinical Studies ( 14.1 )] . 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 [see Clinical Studies (14.2) ] . 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 . 2.2 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. 2.3 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 t …

3 DOSAGE FORMS AND STRENGTHS • 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. ( 3 )

4 CONTRAINDICATIONS None. None. ( 4 )

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • MDS/AML [see Warnings and Precautions ( 5.1 )] • Bone marrow suppression [see Warnings and Precautions ( 5.2 )] • Hypertension and cardiovascular effects [see Warnings and Precautions ( 5.3 )] • Posterior reversible encephalopathy syndrome [see Warnings and Precautions ( 5.4 )] Most common adverse reactions (incidence ≥10%) in patients who received ZEJULA were nausea, thrombocytopenia, anemia, fatigue, constipation, musculoskeletal pain, abdominal pain, vomiting, neutropenia, decreased appetite, leukopenia, insomnia, headache, dyspnea, rash, diarrhea, hypertension, cough, dizziness, acute kidney injury, urinary tract infection, and hypomagnesemia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 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 with rates in the clinical trials of another drug and may not reflect the rates observed in practice. In a pooled safety population of patients (n = 1,314) with advanced ovarian, fallopian tube, or primary peritoneal cancer treated with ZEJULA monotherapy including PRIMA (n = 484), NOVA (n = 367), and another clinical trial (n = 463), the most common adverse reactions >10% were nausea (65%), thrombocytopenia (60%), anemia (56%), fatigue (55%), constipation (39%), musculoskeletal pain (36%), abdominal pain (35%), vomiting (33%), neutropenia (31%), decreased appetite (24%), leukopenia (24%), insomnia (23%), headache (23%), dyspnea (22%), rash (21%), diarrhea (18%), hypertension (17%), cough (16%), dizziness (14%), acute kidney injury (13%), urinary tract infection (12%), and hypomagnesemia (11%). First-Line Maintenance Treatment of HRD-Positive Advanced Ovarian Cancer The safety of ZEJULA for the treatment of patients with advanced ovarian cancer following first-line treatment with platinum-based chemotherapy was studied in the PRIMA trial, a placebo-controlled, double-blind study in which 484 patients received ZEJULA. Among this population, 245 patients were HRD-positive and their median duration of treatment was 13 months (range: 3 days to 29 months). HRD-Positive Patients Receiving ZEJULA in PRIMA: Serious adverse reactions occurred in 30% of patients receiving ZEJULA. Serious adverse reactions in >2% of patients were thrombocytopenia (11%) and anemia (5%). Fatal adverse reactions occurred in 1.6% of patients, including AML (0.4%), cardiac arrest (0.4%), intestinal perforation (0.4%), and sudden death (0.4%). Permanent discontinuation due to adverse reactions occurred in 11% of patients who received ZEJULA. Adverse reactions resulting in permanent discontinuation in >1% of patients who received ZEJULA included thrombocytopenia (3.7%), nausea (1.6%), and anemia (1.2%). Adverse reactions led to dose reduction or interruption in 79% of patients, most frequently (>10%) from thrombocytopenia (53%), anemia (32%), and neutropenia (19%). Tables 4 and 5 summarize the common adverse reactions and abnormal laboratory findings observed in the PRIMA trial. Table 4. Adverse Reactions Reported in ≥10% of HRD-Positive Patients Receiving ZEJULA in PRIMA a AST/ALT = Aspartate aminotransferase/alanine aminotransferase. a All adverse reactions in the table consist of grouped preferred terms except for nausea, vomiting, decreased appetite, headache, and insomnia, which are single preferred terms. b Common Terminology Criteria for Adverse Events version 4.02. c Includes neutropenia, neutropenic infection, neutropenic sepsis, and febrile neutropenia. d Includes leukopenia, lymphocyte count decreased, lymphopenia, and white blood cell count decreased. e Includes blood creatinine increased, blood urea increased, acute kidney injury, and renal failure. Adverse Rea …

8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on its mechanism of action, ZEJULA can cause fetal harm when administered to pregnant women [see Clinical Pharmacology ( 12.1 )] . There are no data regarding the use of ZEJULA in pregnant women to inform the drug-associated risk. 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 ), 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. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. 8.2 Lactation Risk Summary No data are available regarding the presence of niraparib or its metabolites in human milk, or on its effects on the breastfed child or milk production. Because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during treatment with ZEJULA and for 1 month after receiving the last dose. 8.3 Females and Males of Reproductive Potential ZEJULA can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ( 8.1 )] . Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to initiating treatment with ZEJULA. Contraception Females: Advise females of reproductive potential to use effective contraception during treatment with ZEJULA and for 6 months following the last dose. Infertility Males: Based on animal studies, ZEJULA may impair fertility in males of reproductive potential [see Nonclinical Toxicology ( 13.1 )] . 8.4 Pediatric Use The safety and effectiveness of ZEJULA have not been established in pediatric patients. 8.5 Geriatric Use In PRIMA, 39% of patients were aged 65 years or older and 10% were aged 75 years or older. In NOVA, 35% of patients were aged 65 years or older and 8% were aged 75 years or older. No overall differences in safety and effectiveness of ZEJULA were observed between these patients and younger patients but greater sensitivity of some older individuals cannot be ruled out. 8.6 Hepatic Impairment For patients with moderate hepatic impairment, 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 [see Dosage and Administration ( 2.3 , 2.4 )] . Niraparib exposure increased in patients with moderate hepatic impairment (total bilirubin ≥1.5 to 3 x ULN and any AST level). For patients with mild hepatic impairment (total bilirubin ULN), no dosage modification is recommended. The effect of severe hepatic impairment (total bilirubin >3 x ULN and any AST level) on niraparib pharmacokinetics is unknown.

12.1 Mechanism of Action Niraparib is an inhibitor of PARP enzymes, including PARP-1 and PARP-2, that play a role in DNA repair. In vitro studies have shown that niraparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes resulting in DNA damage, apoptosis, and cell death. Increased niraparib‐induced cytotoxicity was observed in tumor cell lines with or without deficiencies in BRCA1/2 . Niraparib decreased tumor growth in mouse xenograft models of human cancer cell lines with deficiencies in BRCA1/2 and in human patient-derived xenograft tumor models with homologous recombination deficiency (HRD) that had either mutated or wild-type BRCA1/2 .

11 DESCRIPTION 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

16 HOW SUPPLIED/STORAGE AND HANDLING ZEJULA is available as oval-shaped, film-coated tablets containing 100 mg, 200 mg, or 300 mg of niraparib free base. ZEJULA 100-mg tablets are gray, debossed with “100” on one side and “Zejula” on the other side. Bottle of 30 tablets (NDC 0173-0909-13). ZEJULA 200-mg tablets are blue, debossed with “200” on one side and “Zejula” on the other side. Bottle of 30 tablets (NDC 0173-0912-13). ZEJULA 300-mg tablets are green, debossed with “300” on one side and “Zejula” on the other side. Bottle of 30 tablets (NDC 0173-0915-13). Store and dispense in the original bottle. Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature] .