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Ovarian cancer, the 5th leading cause of cancer deaths in the U.S., is one of the deadliest gynecologic malignancies due to its mild early symptoms, often leading to late detection. This edition of our Guidelines+ Monograph series explores niraparib (brand name Zejula) from GlaxoSmithKline (GSK), a once-daily oral (PO) PARP inhibitor. It’s FDA-approved as a first-line maintenance treatment for advanced epithelial ovarian, fallopian tube, and primary peritoneal cancer in patients who’ve had a complete or partial response to platinum-based chemotherapy. 

Initially approved by the FDA in 2017 for ovarian cancer, this monograph provides a detailed overview of  niraparib (Zejula), including indications, dosing, administration, and side effects. Information contained in this monograph is current as of August 2024. For the latest drug information and more details about the guidelines contained in this monograph, refer to our guidelines library and medication search toolkit.

Medication Overview: 

• Generic Name: niraparib
• Brand Name: Zejula
• Pharmaceutical Manufacturer: GSK
• FDA Approvals:
  • 2017 received initial FDA approval for epithelial ovarian cancer indication.
  • 2020 received expanded FDA approval for epithelial ovarian, fallopian tube, and primary peritoneal cancers indications.

Indications and FDA Approval Details

Dosage Forms and Strengths

Dosage Form	Strength
Zejula (niraparib) tablets	100 mg
	200 mg
	300 mg

Dosage by Indication and Patient Population

For first-line maintenance treatment of patients who are in complete or partial response to first-line platinum-based chemotherapy:

Indication and Details	Initial Dosage	First Dose Reduction	Second Dose Reduction	Last Dose Reduction
Patients with a baseline weight of <170lbs, or platelets count <1,500/ μL	Zejula (niraparib) 200 mg tablet PO once daily	Zejula (niraparib) 100 mg tablet PO once daily	Discontinue	N/A
Patients with a baseline weight of ≥170lbs, or platelets count ≥1,500/ μL	Zejula (niraparib) 300 mg tablet PO once daily	Zejula (niraparib) 200 mg tablet PO once daily	Zejula (niraparib) 100 mg tablet PO once daily	Discontinue

The recommended dosage of Zejula for maintenance treatment of recurrent germline BRCA-mutated ovarian cancer is 300 mg taken orally once daily.

Additional Dosing Considerations:

• Patients should start treatment with Zejula no later than 12 weeks after their most recent platinum-containing regimen
• No known drug-drug interactions have been reported, though no clinical drug interaction studies have been performed with Zejula
• Tablet should be swallowed whole without crushing, chewing, or splitting tablets
• Zejula should be taken at approximately the same time each day 
• Can be stored at room temperature  
• Can be taken with or without food 
• An additional dose should not be taken if vomiting occurs or the patient misses a dose. The next dose should be taken at its regularly scheduled time.

Warnings and Precautions

Key Warnings and Precautions:

• Cases of Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML), some fatal, have been observed in patients taking Zejula.
• Zejula may lead to bone marrow suppression.
• Hypertension, including severe hypertensive crises, has been associated with Zejula use.
• Zejula poses a risk of causing harm to an unborn baby if administered during pregnancy.

Additional Key Warnings:

• PRES (Posterior Reversible Encephalopathy Syndrome): Monitor for symptoms such as severe headache, confusion, visual disturbances, or seizures, as PRES has been associated with Zejula. Immediate medical intervention is necessary if these symptoms appear.
• Pregnancy and Fertility:
  • Zejula is teratogenic; therefore, ensure female patients of reproductive potential use highly effective contraception during treatment and for six months after the final dose. A pregnancy test should be conducted before initiating therapy, periodically during treatment, and one month post-therapy.
  • Counsel patients on the potential impact of Zejula on fertility.
• Pediatric Use: Zejula is not approved for use in patients under 18 years of age.

Adverse Reactions

Some of the side effects patients could experience are:

• Anemia
• Thrombocytopenia
• Neutropenia
• Nausea and vomiting
• Constipation
• Fatigue
• Insomnia
• Hypertension
• Hematuria
• Cough
• Diarrhea
• Dizziness
• Headache
• Loss of appetite
• Hypomagnesemia
• Muscle and back pain
• Abdominal pain
• Rash
• Dyspnea
• Urinary tract infection

*These are only some of the possible adverse reactions someone may have when taking Zejula. 

Specific Inclusions of Zejula in Clinical Guidelines:

• Somatic Genomic Testing for Metastatic or Advanced Cancer
  • Authoring Society: American Society of Clinical Oncology
  • Publication Date: February 17, 2022
  • Recommendation(s):
    • ASCO lists niraparib as an FDA-approved treatment for specific generic alterations in certain tumor types. These include:
      • Ovarian, fallopian tube, or peritoneal cancers with deleterious or suspected deleterious germline or somatic mutations in BRCA1 and/or BRCA2.
      • Ovarian cancer that is GIS positive and/or HRD positive.

• PARP Inhibitors in the Management of Ovarian Cancer
  • Authoring Society: American Society of Clinical Oncology
  • Publication Date: September 23, 2023
  • Recommendation(s):
    • Patients with newly diagnosed stage III–IV EOC who are in complete or partial response to first-line platinum-based chemotherapy should be offered PARPi maintenance therapy in high-grade serous (HGS) or endometrioid ovarian cancer. For those with germline or somatic pathogenic or likely pathogenic variants in BRCA1 or BRCA2 genes, options should include olaparib (300 mg orally every 12 hours for 2 years), niraparib (200–300 mg orally daily for 3 years) or rucaparib (600 mg twice a day for 2 years). Longer duration could be considered in selected individuals after discussion of risks. For those who are HRD positive, determined using FDA-approved companion diagnostic tests, rucaparib and niraparib are options. Niraparib or rucaparib may be offered for non-BRCAmut/HRDneg patients. (Strong recommendation; EB-B-H)
    • PARPi monotherapy maintenance (second-line or more) may be offered to patients with EOC who have not already received a PARPi and who have responded to platinum-based therapy regardless of BRCA mutation status; treatment is continued until progression of disease or toxicity despite dose reductions and best supportive care. (Strong recommendation; EB-B-H)
      • Options include: olaparib 300 mg every 12 hours, rucaparib 600 mg every 12 hours or niraparib 200–300 mg once daily.
    • Maintenance treatment with niraparib for patients without germline or somatic BRCA mutation should weigh potential PFS benefit against possible overall survival decrement. (Moderate recommendation; EB-B-L)
    • Thrombocytopenia is most common with niraparib. Niraparib dosing guidelines should be used to lower starting dose (200 mg) based on weight and platelet count.

The information provided here on Zejula (niraparib) highlights its role in the ongoing management of epithelial ovarian cancer. As with any medication, it’s crucial to be aware of its indications, dosing, potential side effects, and contraindications to ensure safe and effective use. Sign up for alerts and stay updated with the latest clinical guidelines and evidence-based practices.

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