ZEJULA

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 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 [see Warnings and Precautions ( 5.1 , 5.2 )] . Monitor complete blood counts weekly for the first month, monthly for the next 11 months of treatment, and periodically after this time [see Warnings and Precautions ( 5.2 )] . 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 . 2.4 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 [see Use in Specific Populations ( 8.6 ), Clinical Pharmacology ( 12.3 )] . Monitor patients for hematologic toxicity and reduce the dose, if needed [see Dosage and Administration ( 2.3 )] .

See official label

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.