Data from FDA - Curated by EPG Health - Last updated 05 February 2018

Indication(s)

1 INDICATIONS AND USAGE ZEJULA® is indicated for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. ZEJULA is a poly(ADP-ribose) polymerase (PARP) inhibitor indicated for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.

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Advisory information

contraindications
4 CONTRAINDICATIONS None. None.
Adverse reactions
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)] Most common adverse reactions (incidence ≥10%) are thrombocytopenia, anemia, neutropenia, leukopenia, palpitations, nausea, constipation, vomiting, abdominal pain/distention, mucositis/stomatitis, diarrhea, dyspepsia, dry mouth, fatigue/asthenia, decreased appetite, urinary tract infection, AST/ALT elevation, myalgia, back pain, arthralgia, headache, dizziness, dysgeusia, insomnia, anxiety, nasopharyngitis, dyspnea, cough, rash, and hypertension. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact TESARO at 1-844-4-TESARO 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 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 1-4CTCAE=Common Terminology Criteria for Adverse Events version 4.02 Grades 3-4 ZEJULA N=367 % Placebo N=179 % ZEJULA N=367 % Placebo N=179 % 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 18 12 0 0 Dry mouth 10 4 0.3 0 General Disorders and Administration Site Conditions Fatigue/Asthenia 57 41 8 0.6 Metabolism and Nutrition Disorders Decreased appetite 25 15 0.3 0.6 Infections and Infestations Urinary tract infection 13 8 0.8 1 Investigations AST/ ALT elevation 10 5 4 2 Musculoskeletal and Connective Tissue Disorders Myalgia 19 20 0.8 0.6 Back pain 18 12 0.8 0 Arthralgia 13 15 0.3 0.6 Nervous System Disorders Headache 26 11 0.3 0 Dizziness 18 8 0 0 Dysgeusia 10 4 0 0 Psychiatric Disorders Insomnia 27 8 0.3 0 Anxiety 11 7 0.3 0.6 Respiratory, Thoracic, and Mediastinal Disorders Nasopharyngitis 23 14 0 0 Dyspnea 20 8 1 1 Cough 16 5 0 0 Skin and Subcutaneous Tissue Disorders Rash 21 9 0.5 0 Vascular Disorders Hypertension 20 5 9 2 Table 5: Abnormal Laboratory Findings in ≥25% of Patients Receiving ZEJULA Grades 1-4 Grades 3-4 ZEJULA N=367 (%) Placebo N= 179 (%) ZEJULA N= 367 (%) Placebo N= 179 (%) N=number of patients; WBC=white blood cells; ALT=Alanine aminotransferase; AST=Aspartate aminotransferase Decrease in hemoglobin 85 56 25 0.5 Decrease in platelet count 72 21 35 0.5 Decrease in WBC count 66 37 7 0.7 Decrease in absolute neutrophil count 53 25 21 2 Increase in AST 36 23 1 0 Increase in ALT 28 15 1 2 The following adverse reactions and laboratory abnormalities have been identified in ≥1 to <10% of the 367 patients receiving ZEJULA in the NOVA trial and not included in the table: tachycardia, peripheral edema, hypokalemia, bronchitis, conjunctivitis, gamma-glutamyl transferase increased, blood creatinine increased, blood alkaline phosphatase increased, weight decreased, depression, epistaxis.

Usage information

Dosing and administration
2 DOSAGE AND ADMINISTRATION Recommended dose is 300 mg taken once daily with or without food. (2.1) Continue treatment until disease progression or unacceptable adverse reaction. (2.1, 2.2) For adverse reactions, consider interruption of treatment, dose reduction, or dose discontinuation. (2.2) 2.1 Recommended Dosage The recommended dose of ZEJULA as monotherapy is 300 mg (three 100 mg capsules) taken orally once daily. Instruct patients to take their dose of ZEJULA at approximately the same time each day. Each capsule should be swallowed whole. ZEJULA may be taken with or without food. Bedtime administration may be a potential method for managing nausea. Patients should start treatment with ZEJULA no later than 8 weeks after their most recent platinum-containing regimen. ZEJULA treatment should be continued until disease progression or unacceptable toxicity. 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. 2.2 Dose Adjustments for Adverse Reactions To manage adverse reactions, consider interruption of treatment, dose reduction, or dose discontinuation. The recommended dose modifications for adverse reactions are listed in Tables 1, 2 and 3. Table 1: Recommended dose modifications for adverse reactions Dose level Dose Starting dose 300 mg/day (three 100 mg capsules) First dose reduction 200 mg/day (two 100 mg capsules) Second dose reduction 100 mg/dayIf further dose reduction below 100 mg/day is required, discontinue ZEJULA. (one 100 mg capsule) Table 2: Dose modifications for non-hematologic adverse reactions Non-hematologic CTCAECTCAE=Common Terminology Criteria for Adverse Events ≥ Grade 3 adverse reaction where prophylaxis is not considered feasible or adverse reaction persists despite treatment Withhold ZEJULA for a maximum of 28 days or until resolution of adverse reaction. Resume ZEJULA at a reduced dose per Table 1. Up to 2 dose reductions are permitted. CTCAE ≥ Grade 3 treatment-related adverse reaction lasting more than 28 days while patient is administered ZEJULA 100 mg/day Discontinue medication. Table 3: Dose modifications for hematologic adverse reactions 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 (5.1)]. Platelet count <100,000/µL First occurrence: Withhold ZEJULA for a maximum of 28 days and monitor blood counts weekly until platelet counts return to ≥100,000/µL. Resume ZEJULA at same or reduced dose per Table 1. If platelet count is <75,000/µL, 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/µL. 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.If myelodysplastic syndrome or acute myeloid leukemia (MDS/AML) is confirmed, discontinue ZEJULA [see Warnings and Precautions (5.1, 5.2)]. Neutrophil <1,000/µL 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/µL 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. Hematologic adverse reaction requiring transfusion For patients with platelet count ≤10,000/μL, platelet transfusion should be considered. If there are other risk factors such as co-administration of anticoagulation or antiplatelet drugs, consider interrupting these drugs and/or transfusion at a higher platelet count. Resume ZEJULA at a reduced dose.
Use in special populations
8 USE IN SPECIFIC POPULATIONS Lactation: Advise women not to breastfeed during treatment and for 1 month after receiving the final dose. (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) 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. 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 infant or milk production. Because of the potential for serious adverse reactions in breastfed infants from ZEJULA, advise a lactating woman not to breastfeed during treatment with ZEJULA and for 1 month after receiving the final dose. 8.3 Females and Males of Reproductive Potential Pregnancy Testing ZEJULA can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. A pregnancy test is recommended for females of reproductive potential prior to initiating ZEJULA treatment. Contraception Females ZEJULA can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Advise females of reproductive potential to use effective contraception treatment with ZEJULA and for at least 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 Safety and effectiveness of ZEJULA have not been established in pediatric patients. 8.5 Geriatric Use In Trial 1 (NOVA), 35% of patients were aged ≥65 years and 8% were aged ≥75 years. 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 Renal Impairment No dose adjustment is necessary for patients with mild (CLcr:60 to 89 mL/min) to moderate (CLcr:30 to 59 mL/min) renal impairment. The degree of renal impairment was determined by creatinine clearance as estimated by the Cockcroft-Gault equation. The safety of ZEJULA in patients with severe renal impairment or end stage renal disease undergoing hemodialysis is unknown. 8.7 Hepatic Impairment No dose adjustment is needed in patients with mild hepatic impairment according to the National Cancer Institute – Organ Dysfunction Working Group (NCI-ODWG) criteria. The safety of ZEJULA in patients with moderate to severe hepatic impairment is unknown.

More information

Category Value
Authorisation number NDA208447
Agency product number HMC2H89N35
Orphan designation No
Product NDC 69656-103
Date Last Revised 19-01-2018
Type HUMAN PRESCRIPTION DRUG
Storage and handling 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].
Marketing authorisation holder TESARO, Inc.