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Safety

Safety Profile

PRIMA Clinical Study: An established safety and tolerability profile, in 1LM therapy of advanced ovarian cancer1,2

ARs reported in ≥10% of all patients receiving ZEJULA in PRIMA1*

Adverse reactions reported table

12% of patients discontinued treatment with ZEJULA due to ARs1,2

 

ARs resulting in discontinuation of ZEJULA in >1% of patients included thrombocytopenia (3.7%), anemia (1.9%), and nausea and neutropenia (1.2% each)1

ARs were managed with dose interruptions and modifications.
*All ARs consist of grouped preferred terms except for nausea, vomiting, decreased appetite, headache, and insomnia, which are single preferred terms.
† CTCAE = Common Terminology Criteria for Adverse Events version 4.02.
‡ Includes neutropenia, neutropenic infection, neutropenic sepsis, febrile neutropenia.
§ Includes leukopenia, lymphocyte count decreased, lymphopenia, white blood cell count decreased.
Includes blood creatinine increased, blood urea increased, acute kidney injury, renal failure, and blood creatine increased.

Monitoring

Side effects of ZEJULA may be managed with dose interruption and modification1,2

In PRIMA, adverse events led to dose reduction or interruption in 80% of patients, most frequently from thrombocytopenia (56%), anemia (33%), and neutropenia (20%)1

Monitoring complete blood counts, blood pressure, and heart rate helps identify the need to dose modify1

Blood counts

Monitoring complete blood count infographic

Blood pressure and heart rate

Monitoring blood pressure and heart rate infographic

#Monitor periodically. Per physician discretion.

Individualized Starting Dose

An individualized starting dose in 1LM, giving your patients a tailored dose from the start1,2

If baseline weight <170 lb OR platelets <150,000/μl

200

mg/day

If baseline weight ≥170 lb AND platelets ≥150,000/μl

300

mg/day

For patients with moderate hepatic impairment, reduce the starting dose of ZEJULA to 200 mg once daily. Monitor patients for hematologic toxicity and reduce the dose further, if needed.1

Safety icon

An individualized starting dose was observed to lower rates of select ARs while maintaining efficacy in an exploratory analysis1,3-5||

PRIMA prospectively evaluated the safety and efficacy of an individualized starting dose of either 200 mg or 300 mg, selected based on baseline weight and platelet count, as well as a fixed starting dose of 300 mg1,2

Rates of select grade 3-4 hematologic ARs1,3,4

Bar graph showing hematologic adverse reactions in PRIMA

In PRIMA, patients in the overall and individualized populations experienced the same rates of grades 3-4 leukopenia.1

Rates of select grades 1-4 symptomatic gastrointestinal ARs4

Gastrointestinal adverse reactions bar graph

The efficacy of ZEJULA was maintained in the overall population, HRd, and BRCAm patients taking an individualized starting dose1,3,5||

Overall population

31%

reduction in risk of progression or death observed with ZEJULA in patients in the overall population taking an individualized starting dose based on weight and platelet count vs placebo.1,3

HR, 0.69 (95% CI, 0.48-0.98)

HRd patients

61%

reduction in risk of progression or death observed with ZEJULA in HRd patients taking an individualized starting dose based on weight and platelet count vs placebo.1,3

HR, 0.39 (95% CI, 0.22-0.72)

BRCAm patients

71%

reduction in risk of progression or death observed with ZEJULA in BRCAm patients taking an individualized starting dose based on weight and platelet count vs placebo.5

HR, 0.29 (95% CI, 0.13-0.67)

||Exploratory subgroup analysis, not powered to detect a statistically significant treatment effect. Interpret results with caution.

Long-term Safety Data

In PRIMA, no new safety signals were reported in the 3.5-year median follow-up6

TEAE overview from 3.5-year follow-up of the overall population6

TEAE overview table

With 3.5-year median follow-up, the most common ARs (grades 1-4) in ≥20% of all patients who received ZEJULA in PRIMA were thrombocytopenia (67%), anemia (65%), nausea (58%), neutropenia (43%), constipation (42%), fatigue (37%), headache (28%), insomnia (26%), abdominal pain (25%), vomiting (24%), arthralgia (21%), hypertension (21%), and diarrhea (20%).6

ARs were consistent with the primary analysis and the known safety profile of ZEJULA1,2,6

 

The TEAE-related discontinuation rate was sustained with 3.5-year follow-up1,2,6**

**At the time of the primary analysis of PRIMA, 12% of patients discontinued treatment with ZEJULA due to ARs.1,2

 

ARs resulting in discontinuation of ZEJULA in >1% of patients included thrombocytopenia (3.7%), anemia (1.9%), and nausea and neutropenia (1.2% each).1

ZEJULA DOSING

1LM = first-line maintenance; ALT = alanine transaminase; AR = adverse reaction; AST = aspartate transaminase; BRCA = breast cancer susceptibility gene; BRCAm = BRCA-mutated; CI = confidence interval; HR = hazard ratio; HRd = homologous recombination deficient; TEAE = treatment-emergent adverse event.

Indication & Important Safety Info

Indication

Important Safety Information

Indication

ZEJULA (niraparib) tablets 100 mg/200 mg/300 mg are indicated:

  • for first-line 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

Important Safety Information

Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), including cases with a fatal outcome, have been reported in patients who received ZEJULA. In PRIMA, MDS/AML occurred in 6 out of 484 (1.2%) patients treated with ZEJULA, and in 3 out of 244 (1.2%) patients treated with placebo. The duration of therapy with ZEJULA in patients who developed secondary MDS/cancer therapy-related AML varied from 3.7 months to 2.5 years. All patients who developed secondary MDS/cancer therapy-related AML had received previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy. For suspected MDS/AML or prolonged hematological toxicities, refer the patient to a hematologist for further evaluation. Discontinue ZEJULA if MDS/AML is confirmed.

 

Hematologic adverse reactions (thrombocytopenia, anemia, neutropenia, and/or pancytopenia) have been reported in patients receiving ZEJULA. The overall incidence of Grade ≥3 thrombocytopenia, anemia, and neutropenia were reported, respectively, in 39%, 31%, and 21% of patients receiving ZEJULA in PRIMA. Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred, respectively, in 4%, 2%, and 2% of patients in PRIMA. In patients who were administered a starting dose of ZEJULA based on baseline weight or platelet count in PRIMA, Grade ≥3 thrombocytopenia, anemia, and neutropenia were reported, respectively, in 22%, 23%, and 15% of patients receiving ZEJULA. Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred, respectively, in 3%, 3%, and 2% of patients. 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, 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 6% of patients receiving ZEJULA vs 1% of patients receiving placebo in PRIMA, with no reported discontinuations. Monitor blood pressure and heart rate at least weekly for the first two months, then 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.

 

Posterior reversible encephalopathy syndrome (PRES) occurred in 0.1% of 2,165 patients treated with ZEJULA in clinical trials and has also been described in postmarketing reports. Monitor all patients for signs and symptoms of PRES, which include seizure, headache, altered mental status, visual disturbance, or cortical blindness, with or without associated hypertension. Diagnosis requires confirmation by brain imaging. If suspected, promptly discontinue ZEJULA and administer appropriate treatment. The safety of reinitiating ZEJULA is unknown.

 

Embryo-fetal toxicity and lactation: 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 of ZEJULA. Because of the potential for serious adverse reactions from ZEJULA in breastfed infants, advise lactating women not to breastfeed during treatment with ZEJULA and for 1 month after receiving the last dose.

 

First-line Maintenance Advanced Ovarian Cancer

 

Most common adverse reactions (Grades 1-4) in ≥10% of all patients who received ZEJULA in PRIMA were thrombocytopenia (66%), anemia (64%), nausea (57%), fatigue (51%), neutropenia (42%), constipation (40%), musculoskeletal pain (39%), leukopenia (28%), headache (26%), insomnia (25%), vomiting (22%), dyspnea (22%), decreased appetite (19%), dizziness (19%), cough (18%), hypertension (18%), AST/ALT elevation (14%), and acute kidney injury (12%).

 

Common lab abnormalities (Grades 1-4) in ≥25% of all patients who received ZEJULA in PRIMA included: decreased hemoglobin (87%), decreased platelets (74%), decreased leukocytes (71%), increased glucose (66%), decreased neutrophils (66%), decreased lymphocytes (51%), increased alkaline phosphatase (46%), increased creatinine (40%), decreased magnesium (36%), increased AST (35%), and increased ALT (29%).

 

Please see accompanying Prescribing Information for ZEJULA tablets.

To report SUSPECTED ADVERSE REACTIONS, contact GSK at gsk.public.reportum.com or 1-888-825-5249 or
FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

References

  1. ZEJULA (niraparib) Tablets. Prescribing Information. GSK; 2023.
  2. González‑Martín A, Pothuri B, Vergote I, et al. N Engl J Med. 2019;381(25):2391-2402. doi:10.1056/NEJMoa1910962
  3. Mirza MR, González-Martín A, Graybill WS, et al. Cancer. 2023;1-10. doi:10.1002/cncr.34706
  4. Mirza MR, González-Martín A, Graybill WS, et al. [supplementary appendix]. Cancer. 2023;1-13. doi:10.1002/cncr.34706
  5. Korach J, Graybill W, Redondo A, et al. Int J Gynecol Cancer. 2020;30(suppl 4):A125-A126. doi:10.1136/ijgc-2020-ESGO.220
  6. González-Martín A, Pothuri B, Vergote I, et al. N Engl J Med. 2023;5,112908. doi:10.1016/j.ejca.2023.04.024
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