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ZEJULA SIDE EFFECTS

  • Generic Name: niraparib capsules
  • Brand Name: Zejula
  • Drug Class: Antineoplastics PARP Inhibitors
Last updated on MDtodate: 10/11/2022

SIDE EFFECTS

The following clinically significant adverse reactions are described elsewhere in the labeling:

  • MDS/AML
  • Bone marrow suppression
  • Hypertension and cardiovascular effects
  • Posterior reversible encephalopathy syndrome

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 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 728 patients received niraparib or placebo. Among patients who received ZEJULA, the median duration of treatment was 11.1 months (range: 0.03 to 29 months).

All Patients Receiving ZEJULA In PRIMA

Serious adverse reactions occurred in 32% of patients receiving ZEJULA. Serious adverse reactions in >2% of patients were thrombocytopenia (16%), anemia (6%), and small intestinal obstruction (2.9%). Fatal adverse reactions occurred in 0.4% of patients, including intestinal perforation and pleural effusion (1 patient each).

Permanent discontinuation due to adverse reactions occurred in 12% of patients who received ZEJULA. Adverse reactions resulting in permanent discontinuation in >1% of patients who received ZEJULA included thrombocytopenia (3.7%), anemia (1.9%), and nausea and neutropenia (1.2% each).

Adverse reactions led to dose reduction or interruption in 80% of patients, most frequently from thrombocytopenia (56%), anemia (33%), and neutropenia (20%).

Table 1 and Table 2 summarize the common adverse reactions and abnormal laboratory findings, respectively, observed in all patients treated with ZEJULA in the PRIMA study.

Table 1: Adverse Reactions Reported in ≥10% of All Patients Receiving ZEJULA in PRIMAa

Adverse Reaction Grades 1-4b Grades 3-4b
ZEJULA
(n = 484) %
Placebo
(n = 244) %
ZEJULA
(n = 484) %
Placebo
(n = 244) %
Blood and lymphatic system disorders
Thrombocytopenia 66 5 39 0.4
Anemia 64 18 31 2
Neutropeniac 42 8 21 1
Leukopeniad 28 9 5 0.4
Gastrointestinal disorders
Nausea 57 28 1 1
Constipation 40 20 1 0.4
Vomiting 22 12 1 1
General disorders and administration site conditions
Fatigue 51 41 3 1
Investigations AST/ALT elevation 14 7 3 0.8
Metabolism and nutrition disorders
Decreased appetite 19 8 1 0
Musculoskeletal and connective tissue disorders
Musculoskeletal pain 39 38 1 0
Nervous system disorders
Headache 26 15 0.4 0
Dizziness 19 13 0 0.4
Psychiatric disorders
Insomnia 25 15 1 0.4
Renal and urinary disorders
Acute kidney injurye 12 5 0.2 0
Respiratory, thoracic, and mediastinal disorders
Dyspnea 22 13 0.4 1
Cough 18 15 0 0.4
Vascular disorders
Hypertension 18 7 6 1
AST/ALT = Aspartate transaminase/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, renal failure, and blood creatine increased.

 

Table 2: Abnormal Laboratory Findings in ≥25% of All Patients Receiving ZEJULA in PRIMA

Abnormal Laboratory Finding Grades 1-4 Grades 3-4
ZEJULA
(n = 484) %
Placebo
(n = 244) %
ZEJULA
(n = 484) %
Placebo
(n = 244) %
Decreased hemoglobin 87 66 29 1
Decreased platelets 74 13 37 0
Decreased leukocytes 71 36 9 0
Increased glucose 66 57 3 3
Decreased neutrophils 66 25 23 1
Decreased lymphocytes 51 29 7 3
Increased alkaline phosphatase 46 21 1 0
Increased creatinine 40 23 0 0
Decreased magnesium 36 34 1 0
Increased aspartate aminotransferase 35 17 1 0.4
Increased alanine aminotransferase 29 17 2 1

 

Patients Receiving ZEJULA With Dose Based On Baseline Weight Or Platelet Count In PRIMA

Among patients who received ZEJULA with the dose based on weight and platelet count, the median duration of treatment was 11 months (range: 1 day to 16 months).

Serious adverse reactions occurred in 27% of patients receiving ZEJULA. Serious adverse reactions in >2% of patients were anemia (8%), and thrombocytopenia (7%). No fatal adverse reactions occurred.

Permanent discontinuation due to adverse reactions occurred in 14% of patients who received ZEJULA. Adverse reactions resulting in permanent discontinuation in >2% of patients who received ZEJULA included thrombocytopenia and anemia (3% each) and nausea (2.4%).

Adverse reactions led to dose reduction or interruption in 72% of patients, most frequently from thrombocytopenia (40%), anemia (23%), and neutropenia (15%).

Table 3 and Table 4 summarize adverse reactions and abnormal laboratory findings in the group of patients who received ZEJULA.

Table 3: Adverse Reactions Reported in ≥10% of Patients Receiving ZEJULA Based on Baseline Weight or Platelet Count in PRIMAa

Adverse Reaction Grades 1-4b Grades 3-4b
ZEJULA
(n = 169) %
Placebo
(n = 86) %
ZEJULA
(n = 169) %
Placebo
(n = 86) %
Blood and lymphatic system disorders
Thrombocytopenia 54 5 21 1
Anemia 50 28 23 1
Neutropeniac 36 8 15 1
Leukopeniad 28 11 5 0
Gastrointestinal disorders
Nausea 53 21 1 0
Constipation 31 15 1 1
Vomiting 17 9 0 1
General disorders and administration site conditions
Fatigue 48 36 3 0
Metabolism and nutrition disorders
Decreased appetite 19 5 1 0
Nervous system disorders
Headache 22 17 1 0
Dizziness 14 13 0 0
Psychiatric disorders
Insomnia 21 14 0 0
Renal and urinary disorders
Acute kidney injurye 12 5 1 0
Respiratory, thoracic, and mediastinal disorders Dyspnea 18 10 0 1
Vascular disorders
Hypertension 17 9 5 2
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, renal failure, and blood creatine increased.

 

Table 4: Abnormal Laboratory Findings in ≥25% of All Patients Receiving ZEJULA Based on Baseline Weight or Platelet Count in PRIMA

Abnormal Laboratory Finding Grades 1-4 Grades 3-4
ZEJULA
(n = 169) %
Placebo
(n = 86) %
ZEJULA
(n = 169) %
Placebo
(n = 86) %
Decreased hemoglobin 81 70 21 0
Decreased leukocytes 70 36 6 0
Decreased platelets 63 15 18 0
Increased glucose 63 56 2 1
Decreased neutrophils 60 27 15 0
Decreased lymphocytes 52 30 5 4
Increased alkaline phosphatase 43 17 1 0
Decreased magnesium 44 30 0 0
Increased creatinine 41 22 0 0
Increased aspartate aminotransferase 31 19 1 0
Increased alanine aminotransferase 28 15 2 2

 

Maintenance Treatment Of Recurrent Ovarian Cancer

The safety of monotherapy with ZEJULA 300 mg once daily has been studied in 367 patients with platinum-sensitive recurrent ovarian, fallopian tube, and primary peritoneal cancer in the NOVA trial. Adverse reactions in NOVA 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 NOVA was 15%. The median exposure to ZEJULA in these patients was 250 days.

Table 5 and Table 6 summarize the common adverse reactions and abnormal laboratory findings, respectively, observed in patients treated with ZEJULA in NOVA.

Table 5: Adverse Reactions Reported in ≥10% of Patients Receiving ZEJULA in NOVA

Adverse Reaction Grades 1-4a Grades 3-4a
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
Neutropeniab 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
Mucositis/stomatiti s 20 6 0.5 0
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
Back pain 18 12 0.8 0
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
AST/ALT = Aspartate transaminase/alanine aminotransferase.
a Common Terminology Criteria for Adverse Events version 4.02.
b Includes preferred terms of neutropenic infection, neutropenic sepsis, and febrile neutropenia.

 

Table 6: Abnormal Laboratory Findings in ≥25% of Patients Receiving ZEJULA in NOVA

Abnormal Laboratory Finding Grades 1-4 Grades 3-4
ZEJULA
(n = 367) %
Placebo
(n = 179) %
ZEJULA
(n = 367) %
Placebo
(n = 179) %
Decrease in hemoglobin 85 56 25 0.5
Decrease in platelet count 72 21 35 0.5
Decrease in white blood cell count 66 37 7 0.7
Decrease in absolute neutrophil count 53 25 21 2
Increase in aspartate aminotransferase 36 23 1 0
Increase in alanine aminotransferase 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, and epistaxis.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of ZEJULA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Blood And Lymphatic System Disorders

Pancytopenia.

Immune System Disorders

Hypersensitivity (including anaphylaxis).

Nervous System Disorders

Posterior reversible encephalopathy syndrome (PRES).

Psychiatric Disorders

Confusional state/disorientation, hallucination, cognitive impairment (e.g., memory impairment, concentration impairment).

Respiratory, Thoracic, And Mediastinal Disorders

Non-infectious pneumonitis.

Skin And Subcutaneous Tissue Disorders

Photosensitivity.

Vascular Disorders

Hypertensive crisis.

 

SRC: NLM .

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