What Is Niraparib (Zejula)? FDA Approval, Licensing in Türkiye, and Reimbursement
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Zejula (Niraparib) Profile
- FDA-approved: Yes (first approved on 27 March 2017)
- Brand name: Zejula
- Active ingredient: Niraparib
- Route of administration: Oral, in capsule and tablet forms
- Class: Signal transduction inhibitor, PARP inhibitor
- Category: Targeted agent
- Manufacturer: GlaxoSmithKline
- Distribution in Türkiye: GlaxoSmithKline İlaçları San. ve Tic. A.Ş.
- Cancers for which it is approved: Advanced epithelial ovarian, fallopian tube, or primary peritoneal cancers.
What Is Zejula? How Does It Work?
Containing the active ingredient niraparib, Zejula is an oral treatment used for maintenance of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancers. It is a PARP inhibitor. It aims to slow disease progression, particularly in patients who respond to platinum-based chemotherapy and carry a BRCA mutation.
PARP Inhibition and Mechanism of Action
PARP inhibitors act on DNA damage repair in cells by targeting the poly(ADP-ribose) polymerase (PARP) enzyme, Niraparib inhibits PARP1 and PARP2, leading to increasing PARP-DNA complexes and resulting in cell death. This mechanism increases antitumor activity in tumors with BRCA deficiency, while also enhancing radiotherapy’s effects through a P53-independent pathway.
FDA (US Food and Drug Administration) Approval History
- 27 March 2017: Approved for maintenance treatment in adults with recurrent ovarian, fallopian tube, or primary peritoneal cancer whose tumors had completely or partially shrunk with prior platinum-based chemotherapy.
- 23 October 2019: Approved for patients with advanced cancer who had received three or more chemotherapy regimens and whose cancer was positive for homologous recombination deficiency (HRD).
- 29 April 2020: Approved for women with platinum-responsive advanced ovarian cancer, regardless of biomarker status, as first-line maintenance monotherapy.
Licensing in Türkiye (Therapeutic Indications)
1. First-Line Ovarian Cancer Maintenance Treatment: Indicated for patients with FIGO stage 3 or 4 high-grade serous ovarian cancer, a complete or partial response after first-line platinum chemotherapy, and ECOG PS 0-1, until disease progression or for a maximum of 3 years.
2. Maintenance Treatment for Recurrent Ovarian Cancer: Used as monotherapy in patients with platinum-sensitive high-grade serous ovarian cancer (recurring after at least 6 months) who respond to platinum chemotherapy given for recurrence and are BRCA mutation (BRCA1/2)-positive, confirmed by an accredited laboratory test.
Reimbursement in Türkiye (SGK)
- First-Line: Reimbursed for FIGO stage III or IV patients with BRCA1/2 mutations who achieve a complete/partial response after platinum-based treatment, provided treatment starts no later than 12 weeks after the last platinum dose (for a maximum of 3 years).
- Recurrent: Covered by SGK for platinum-sensitive patients with BRCA1/2 mutations who respond to platinum therapy given for recurrence, provided treatment starts no later than 8 weeks after the last platinum dose. These are the reimbursement conditions.
Price: As of June 2026, ZEJULA 100 mg hard capsules: 134,964.96 TL; 100 mg tablets: 119,372.92 TL.
At the commonly used dose of 200 mg/day, 28 days of treatment cost approximately 119,372.92 TL; at 300 mg/day, approximately 179,059.38 TL.
Resistance Mechanisms
- P-glycoprotein: Increased expression of the drug efflux transporter protein.
- 53BP1 Loss: Reduced expression of p53-binding protein 1, which prevents repair of DNA double-strand breaks.
- Reversion Mutations: Mutations restoring function in BRCA1 or BRCA2.
- REV7 Loss: Restoration of homologous recombination, leading to PARP resistance.
- Increased PARP enzyme expression and increased stabilization of replication forks.
Pharmacokinetic Information
| Absorption | Bioavailability is 73%. Absorption is rapid (peak concentration: 3 hours). Food does not change systemic exposure (AUC). |
| Distribution | Plasma protein binding is 83%. Steady-state blood levels are reached in 3-4 days. |
| Metabolism & Excretion | It is metabolized in the liver through CYP3A4 and carboxylesterases (to the inactive M1 metabolite). Excretion is 48% in urine and 39% in feces. Half-life: 36 hours. |
Dose Range and Use
First-Line Maintenance (Individualized Starting Dose):
- Body weight >77 kg AND platelet count >150,000/µL: daily dose of 300 mg (3 tablets/capsules).
- Body weight <77 kg OR platelet count <150,000/µL: daily dose of 200 mg (2 tablets/capsules).
Drug Interactions and Precautions
- May increase levels of metformin, dabigatran, statins, and methotrexate; caution is required.
- CYP1A2 substrates: Caution is recommended when used with theophylline or clozapine.
- Because of the risk of thrombocytopenia, there is a warning about use with anticoagulants. This combination requires caution.
- During the first year of treatment, blood pressure and heart rate should be monitored monthly. Monitoring should be maintained.
- No dose adjustment is required for mild/moderate kidney impairment or mild liver impairment.
Adverse Effects
- Bone marrow suppression (anemia, thrombocytopenia, and neutropenia).
- Fatigue, loss of appetite, and asthenia.
- Nausea, vomiting, abdominal pain, diarrhea, and constipation.
- Joint, muscle, and back pain.
- Risk of urinary tract infection.
- MDS and AML risk is increased.
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