Safety and Tolerability Profile for ZEJULA1

The safety of ZEJULA monotherapy (300 mg once daily) was studied in 367 patients with platinum-sensitive recurrent ovarian, fallopian tube, and primary peritoneal cancer in the NOVA trial.

Adverse reactions (ARs) reported in ≥10% of patients receiving ZEJULA

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
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

a Based on Common Terminology Criteria for Adverse Events, version 4.02.

Abnormal laboratory findings in ≥25% of patients receiving ZEJULA

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
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

ALT, alanine aminotransferase; AST, aspartate aminotransferase; WBC, white blood cell.

  • The permanent discontinuation rate due to ARs was 15%

Because clinical trials are conducted under widely varying conditions, AR 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.

Please see Important Safety Information below and full Prescribing Information. View dosing information
Indication and Important Safety Information for ZEJULA

Indication

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.

Important Safety Information

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML), including some fatal cases, was reported in 1.4% of patients receiving ZEJULA vs 1.1% of patients receiving placebo in Trial 1 (NOVA), and 0.9% of patients treated with ZEJULA in all clinical studies. The duration of ZEJULA treatment in patients prior to developing MDS/AML varied from <1 month to 2 years. All patients had received prior chemotherapy with platinum and some had also received other DNA damaging agents and radiotherapy. Discontinue ZEJULA if MDS/AML is confirmed.

Hematologic adverse reactions (thrombocytopenia, anemia and neutropenia) have been reported in patients receiving ZEJULA. Grade ≥3 thrombocytopenia, anemia and neutropenia were reported in 29%, 25%, and 20% of patients receiving ZEJULA, respectively. Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred, in 3%, 1%, and 2% of patients, respectively. Do not start ZEJULA until patients have recovered from hematological toxicity caused by prior chemotherapy (≤ Grade 1). Monitor complete blood counts weekly for the first month, monthly for the next 11 months of treatment, and periodically thereafter. If hematological toxicities do not resolve within 28 days following interruption, discontinue ZEJULA, and refer the patient to a hematologist for further investigations.

Hypertension and hypertensive crisis have been reported in patients receiving ZEJULA. Grade 3-4 hypertension occurred in 9% of patients receiving ZEJULA vs 2% of patients receiving placebo in Trial 1, with discontinuation occurring in <1% of patients. Monitor blood pressure and heart rate 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. Manage hypertension with antihypertensive medications and adjustment of the ZEJULA dose, if necessary.

Based on its mechanism of action, ZEJULA can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months after receiving their final dose. Because of the potential for serious adverse reactions from ZEJULA in breastfed infants, advise lactating women to not breastfeed during treatment with ZEJULA and for 1 month after receiving the final dose.

In clinical studies, the most common adverse reactions (Grades 1-4) in ≥10% of patients included: thrombocytopenia (61%), anemia (50%), neutropenia (30%), leukopenia (17%), palpitations (10%), nausea (74%), constipation (40%), vomiting (34%), abdominal pain/distention (33%), mucositis/stomatitis (20%), diarrhea (20%), dyspepsia (18%), dry mouth (10%), fatigue/asthenia (57%), decreased appetite (25%), urinary tract infection (13%), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) elevation (10%), myalgia (19%), back pain (18%), arthralgia (13%), headache (26%), dizziness (18%), dysgeusia (10%), insomnia (27%), anxiety (11%), nasopharyngitis (23%), dyspnea (20%), cough (16%), rash (21%) and hypertension (20%).

Common lab abnormalities (Grades 1-4) in ≥25% of patients included: decrease in hemoglobin (85%), decrease in platelet count (72%), decrease in white blood cell count (66%), decrease in absolute neutrophil count (53%), increase in AST (36%) and increase in ALT (28%).

Reference: 1. ZEJULA [package insert]. Waltham, MA: TESARO, Inc; 2017.