Zejula: Uses, Dosage & Side Effects
A PARP inhibitor used as maintenance therapy for ovarian, fallopian tube, and primary peritoneal cancer following response to platinum-based chemotherapy
Zejula (niraparib) is a prescription oral PARP inhibitor used as maintenance therapy for adult women with epithelial ovarian, fallopian tube, or primary peritoneal cancer. It works by blocking poly(ADP-ribose) polymerase (PARP) enzymes that cancer cells need to repair damaged DNA. When PARP is inhibited, cancer cells—particularly those with existing DNA repair defects such as BRCA mutations or homologous recombination deficiency (HRD)—accumulate lethal DNA damage and die. Zejula is taken as a once-daily oral tablet and has been shown in major clinical trials (PRIMA and NOVA) to significantly prolong progression-free survival in patients whose cancer has responded to platinum-based chemotherapy. Regular blood count monitoring is essential during treatment due to the risk of myelosuppression.
Quick Facts: Zejula
Key Takeaways
- Zejula (niraparib) is a PARP inhibitor approved as maintenance therapy for ovarian, fallopian tube, and primary peritoneal cancer after response to platinum-based chemotherapy, both as first-line maintenance and after recurrence.
- Unlike some other PARP inhibitors, Zejula has demonstrated efficacy in patients both with and without BRCA mutations, making it a broadly applicable maintenance therapy option.
- The PRIMA and NOVA trials showed Zejula significantly prolongs progression-free survival, with the greatest benefit seen in patients with BRCA mutations or homologous recombination deficiency (HRD).
- Common side effects include low blood counts (thrombocytopenia, anemia, neutropenia), nausea, fatigue, and high blood pressure, requiring regular blood monitoring and potential dose adjustments.
- Zejula is taken once daily as an oral tablet (200 mg or 300 mg depending on body weight and platelet count for first-line maintenance; 300 mg for recurrent disease), and taking it at bedtime may help reduce nausea.
What Is Zejula and What Is It Used For?
Zejula contains the active substance niraparib, a potent and selective inhibitor of poly(ADP-ribose) polymerase (PARP) enzymes, specifically PARP-1 and PARP-2. PARP enzymes play a critical role in the repair of single-strand DNA breaks through a process known as base excision repair. When a cell encounters a single-strand DNA break, PARP detects the damage, binds to the break site, and recruits repair proteins to fix the damage. This is a normal and essential process in healthy cells, but cancer cells—particularly those with existing defects in other DNA repair pathways—are especially dependent on PARP-mediated repair for survival.
When niraparib inhibits PARP, the enzyme becomes trapped on damaged DNA, preventing the normal repair of single-strand breaks. These unrepaired single-strand breaks eventually progress to double-strand breaks during DNA replication. In healthy cells with functional homologous recombination repair (HRR), these double-strand breaks can be accurately repaired using the sister chromatid as a template. However, in cancer cells that carry mutations in genes involved in HRR—such as BRCA1, BRCA2, or other genes in the homologous recombination pathway—these double-strand breaks cannot be efficiently repaired. The accumulation of unrepaired double-strand breaks leads to genomic instability, cell cycle arrest, and ultimately programmed cell death (apoptosis). This concept is known as synthetic lethality: neither the loss of PARP function nor the loss of HRR function alone is lethal to the cell, but the combination of both deficiencies is.
Importantly, niraparib has demonstrated antitumor activity in ovarian cancer cells regardless of their BRCA mutation status or HRD status. While the mechanism of synthetic lethality provides the strongest rationale for efficacy in BRCA-mutated and HRD-positive tumors, niraparib also exerts cytotoxic effects in tumors without identified HRR defects. This may be due to additional mechanisms including PARP trapping (where the drug-PARP complex itself becomes a toxic lesion on DNA), replication fork instability, and effects on other DNA damage response pathways.
Approved Indications
Zejula is approved for use in adult women for the maintenance treatment of cancer of the ovaries, fallopian tubes, or peritoneum (the membrane lining the abdominal cavity) in two clinical settings:
- First-line maintenance therapy: For patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response after first-line platinum-based chemotherapy. The PRIMA/ENGOT-OV26 trial demonstrated that niraparib significantly improved progression-free survival in this setting across the overall population, with the most pronounced benefit in patients with HRD-positive tumors.
- Maintenance therapy after recurrence: For patients with platinum-sensitive relapsed ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. The NOVA/ENGOT-OV16 trial showed significant improvements in progression-free survival, particularly in patients with germline BRCA mutations (gBRCA), but also in patients without gBRCA mutations.
Clinical Trial Evidence
The efficacy of Zejula has been established through two pivotal phase III clinical trials that have shaped the modern treatment landscape for ovarian cancer:
PRIMA/ENGOT-OV26 Trial: This randomized, double-blind, placebo-controlled trial enrolled 733 patients with newly diagnosed advanced ovarian cancer who had achieved a complete or partial response after first-line platinum-based chemotherapy. Patients were randomized 2:1 to receive niraparib (at an individualized starting dose of 200 mg or 300 mg once daily based on body weight and baseline platelet count) or placebo. The primary endpoint was progression-free survival (PFS) in the HRD-positive population and then the overall population. In the HRD-positive population, median PFS was 21.9 months with niraparib versus 10.4 months with placebo (hazard ratio 0.43, p<0.001). In the overall population, median PFS was 13.8 months versus 8.2 months (hazard ratio 0.62, p<0.001).
NOVA/ENGOT-OV16 Trial: This randomized, double-blind, placebo-controlled trial enrolled 553 patients with platinum-sensitive, recurrent ovarian cancer who had responded to their most recent platinum-based regimen. Patients were stratified by germline BRCA mutation status. In the gBRCA-mutated cohort, median PFS was 21.0 months with niraparib versus 5.5 months with placebo (hazard ratio 0.27, p<0.001). In the non-gBRCA cohort, median PFS was 9.3 months versus 3.9 months (hazard ratio 0.45, p<0.001). These results demonstrated that niraparib provides clinically meaningful benefit across all biomarker subgroups.
Zejula was first approved by the U.S. Food and Drug Administration (FDA) in March 2017 and subsequently by the European Medicines Agency (EMA) in November 2017. It is now approved in more than 50 countries worldwide and is recommended in major clinical practice guidelines from ESMO (European Society for Medical Oncology) and NCCN (National Comprehensive Cancer Network) as a standard maintenance therapy option for eligible patients with ovarian cancer.
The concept of synthetic lethality is central to understanding how Zejula works. Normal cells have multiple DNA repair pathways that serve as backup systems. When Zejula blocks PARP-mediated repair, healthy cells can still fix DNA damage using alternative pathways like homologous recombination. However, cancer cells that already have defects in these backup pathways (such as BRCA mutations) lose their last line of defense, leading to an overwhelming accumulation of DNA damage and cell death. This targeted approach allows Zejula to preferentially kill cancer cells while sparing most normal cells.
What Should You Know Before Taking Zejula?
Contraindications
Zejula must not be used if you have a known hypersensitivity (allergy) to niraparib or to any of the other ingredients in the tablet. The inactive ingredients include crospovidone, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone, colloidal hydrated silica, polyvinyl alcohol, titanium dioxide, macrogol, talc, and black iron oxide. If you have a known allergy to any of these substances, inform your doctor before starting treatment.
Zejula must also not be used during breastfeeding. It is not known whether niraparib passes into breast milk, and a risk to the breastfed infant cannot be excluded. If you are breastfeeding, you must stop before starting Zejula treatment, and you must not resume breastfeeding until at least 1 month after taking the last dose.
Warnings and Precautions
Before and during treatment with Zejula, talk to your doctor, pharmacist, or nurse about any of the following conditions, as they may affect how your treatment is managed:
Zejula can cause significant decreases in blood cell counts, including red blood cells (anemia), white blood cells (neutropenia and leukopenia), and platelets (thrombocytopenia). Your doctor will perform blood tests regularly during treatment—typically weekly for the first month, then monthly thereafter. Watch for signs of low blood counts: unusual bruising or bleeding, fever, infection, extreme tiredness, shortness of breath, or pale skin. Report these symptoms to your doctor immediately.
Low blood counts (myelosuppression): This is the most common and clinically significant side effect of Zejula. Thrombocytopenia (low platelets) can lead to increased bruising and bleeding risk. Anemia (low red blood cells) can cause fatigue, weakness, shortness of breath, and pale skin. Neutropenia (low white blood cells) increases the risk of infections, which in some cases can be severe and life-threatening. Your doctor will adjust your dose or temporarily pause treatment if blood counts drop too low. Blood count monitoring is typically performed weekly during the first month, then monthly for the next 10 months, and periodically thereafter.
Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML): In rare cases, low blood counts may be a sign of more serious bone marrow problems such as MDS or AML. These are serious blood cancers that have been reported in patients treated with PARP inhibitors, including niraparib. The risk appears to be increased in patients who have received prior chemotherapy. Your doctor may perform bone marrow examinations if there is concern about these conditions. If MDS or AML is diagnosed, Zejula treatment will be permanently discontinued.
Zejula can cause high blood pressure (hypertension), which in some cases can be severe and require urgent medical attention. Your doctor will monitor your blood pressure regularly throughout treatment. Antihypertensive medications may be prescribed, and your Zejula dose may need to be adjusted. You may be advised to monitor your blood pressure at home. Seek medical attention if your blood pressure is consistently elevated or if you experience severe headache, visual changes, or chest pain.
Posterior reversible encephalopathy syndrome (PRES): A rare neurological side effect called PRES has been associated with Zejula treatment. PRES is a condition characterized by headache, visual disturbances (blurred vision, visual loss), seizures, and confusion, often accompanied by high blood pressure. If you experience any of these symptoms, contact your doctor immediately. PRES requires prompt medical evaluation and management, and if confirmed, Zejula treatment should be discontinued.
Children and Adolescents
Zejula should not be used in children and adolescents under 18 years of age. The safety and efficacy of niraparib have not been studied in this age group. Ovarian cancer is primarily a disease of adults, and the use of PARP inhibitors in pediatric populations has not been established.
Other Medications
Tell your doctor or pharmacist about all medications you are taking, have recently taken, or might take. Zejula can affect how certain other medications work. It is particularly important to mention if you are taking metformin (used to lower blood sugar levels in diabetes), as your doctor may need to adjust your metformin dose. Niraparib inhibits the MATE1 and MATE2K renal transporters, which are involved in the excretion of metformin, potentially leading to increased metformin levels in the blood.
Pregnancy and Breastfeeding
Zejula must not be taken during pregnancy, as it may cause harm to the developing baby. Based on its mechanism of action (inhibiting DNA repair), niraparib is expected to cause fetal harm. If you are pregnant, think you may be pregnant, or are planning to become pregnant, do not take Zejula and consult your doctor immediately.
Women of childbearing potential must use highly effective contraception during Zejula treatment and for 6 months after taking the last dose. Your doctor will ask you to take a pregnancy test before starting treatment to confirm that you are not pregnant. If you become pregnant while taking Zejula, contact your doctor immediately.
Breastfeeding is contraindicated during Zejula treatment (see Contraindications above). If you are breastfeeding, you must stop before starting Zejula, and you must not resume breastfeeding until at least 1 month after taking the last dose. Discuss with your doctor the best approach for infant feeding during your treatment.
Driving and Operating Machinery
Zejula may cause weakness, difficulty concentrating, tiredness, or dizziness that can affect your ability to drive and use machines. If you experience any of these symptoms, exercise caution when driving or operating machinery. These side effects are particularly common during the early weeks of treatment and during dose adjustments.
Important Information About Ingredients
Zejula tablets contain lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine. Each 100 mg tablet contains a small amount of lactose monohydrate as an excipient.
How Does Zejula Interact with Other Drugs?
Understanding the drug interaction profile of Zejula is important for patients who are often taking multiple medications for cancer treatment, supportive care, and management of other health conditions. Niraparib has a relatively favorable pharmacokinetic profile from a drug interaction perspective, primarily because it is not extensively metabolized by cytochrome P450 (CYP) enzymes. Instead, niraparib undergoes primary metabolism via carboxylesterases to form a major inactive metabolite, which is then subsequently glucuronidated.
In vitro studies have shown that niraparib is a weak inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. At clinically relevant concentrations, niraparib is not expected to significantly affect the metabolism of co-administered drugs that are substrates of these enzymes. However, niraparib has been identified as an inhibitor of certain drug transporters, which has implications for specific co-administered medications.
The most clinically relevant interaction involves metformin. Niraparib inhibits the MATE1 (multidrug and toxin extrusion protein 1) and MATE2K renal transporters, which are involved in the tubular secretion of metformin in the kidneys. Inhibition of these transporters can reduce renal clearance of metformin, potentially leading to increased plasma concentrations and an elevated risk of lactic acidosis. If you are taking metformin, your doctor may need to monitor your blood glucose levels more closely and consider adjusting your metformin dose.
| Drug / Drug Class | Interaction Mechanism | Clinical Significance | Action Required |
|---|---|---|---|
| Metformin | MATE1/MATE2K transporter inhibition | Moderate – may increase metformin levels | Monitor blood glucose; dose adjustment may be needed |
| P-gp substrates | Weak P-glycoprotein inhibition | Low – unlikely to be clinically significant | No specific action; monitor if co-administered |
| CYP substrates | Weak CYP enzyme inhibition | Low – not expected to be significant | No dose adjustment required |
| Platinum-based chemotherapy | Sequential use (not concurrent) | Low – Zejula is maintenance therapy after chemotherapy | Allow adequate recovery from chemotherapy before starting |
| Anticoagulants | Additive bleeding risk due to thrombocytopenia | Moderate – pharmacodynamic interaction | Monitor platelet counts closely; assess bleeding risk |
| Antihypertensives | Zejula can raise blood pressure | Moderate – may counteract antihypertensive effect | Monitor blood pressure; adjust antihypertensive dose as needed |
Niraparib is also an inhibitor of P-glycoprotein (P-gp) and BCRP (breast cancer resistance protein) transporters in vitro. However, at therapeutic doses, the clinical significance of this inhibition is considered low. Nonetheless, if you are taking narrow therapeutic index drugs that are P-gp substrates (such as digoxin or dabigatran), your doctor may want to monitor you more closely.
It is important to note that while niraparib does not have extensive pharmacokinetic drug interactions, there are important pharmacodynamic considerations. Because Zejula causes thrombocytopenia, concurrent use with anticoagulants (such as warfarin, heparin, or direct oral anticoagulants) or antiplatelet agents (such as aspirin or clopidogrel) may increase the risk of bleeding. Similarly, because Zejula can cause hypertension, patients taking antihypertensive medications may require dose adjustments.
Always inform your doctor and pharmacist about all medications, supplements, and herbal products you are taking before starting Zejula. While the drug interaction profile is relatively favorable, monitoring is important especially for metformin, anticoagulants, and blood pressure medications. Your healthcare team will coordinate any necessary dose adjustments.
What Is the Correct Dosage of Zejula?
Always take Zejula exactly as your doctor or pharmacist has instructed. Your doctor will determine the most appropriate starting dose based on your specific clinical situation, body weight, and blood test results. Do not change your dose without consulting your doctor.
First-Line Maintenance Therapy
For patients with ovarian cancer that has responded to first-line platinum-based chemotherapy, the recommended starting dose is individualized based on body weight and baseline platelet count:
| Patient Criteria | Starting Dose | Tablets per Day | Frequency |
|---|---|---|---|
| Weight <77 kg OR platelets <150,000/µL | 200 mg | 2 tablets (100 mg each) | Once daily |
| Weight ≥77 kg AND platelets ≥150,000/µL | 300 mg | 3 tablets (100 mg each) | Once daily |
This individualized dosing approach was introduced based on findings from the PRIMA trial, where patients with lower body weight or lower baseline platelet counts were more susceptible to hematologic toxicity. By starting at a lower dose in these patients, the risk of severe thrombocytopenia and dose interruptions was reduced while maintaining therapeutic efficacy.
Recurrent Disease Maintenance Therapy
For patients with recurrent ovarian cancer that has responded to platinum-based chemotherapy, the recommended starting dose is 300 mg (three 100 mg tablets) taken once daily. This higher starting dose was used in the NOVA trial and was shown to be effective and generally well-tolerated in this patient population.
How to Take Zejula
Zejula tablets should be swallowed whole with water. The medication can be taken either without food (at least 1 hour before or 2 hours after a meal) or with a light meal. Taking Zejula at approximately the same time each day helps maintain consistent drug levels. Taking Zejula at bedtime is specifically recommended as a strategy to reduce nausea, which is one of the most commonly reported side effects.
Dose Adjustments for Side Effects
If you experience side effects such as low blood counts, nausea, fatigue, or abnormal bleeding/bruising, your doctor may recommend a dose reduction or temporary treatment interruption. Dose reductions follow a stepwise approach:
| Dose Level | Daily Dose | Tablets |
|---|---|---|
| Starting dose (high) | 300 mg | 3 × 100 mg |
| Starting dose (individualized) | 200 mg | 2 × 100 mg |
| First reduction | 200 mg or 100 mg | 2 × 100 mg or 1 × 100 mg |
| Minimum effective dose | 100 mg | 1 × 100 mg |
If the dose needs to be reduced below 100 mg once daily, your doctor will consider whether to discontinue Zejula treatment. Your doctor will perform regular check-ups, and you will generally continue taking Zejula for as long as you benefit from the treatment and do not experience unacceptable side effects.
Special Populations
Your doctor may adjust the starting dose if you have liver problems (hepatic impairment). No dose adjustment is required for patients with mild hepatic impairment. For patients with moderate hepatic impairment, a reduced starting dose of 200 mg once daily is recommended. Zejula has not been studied in patients with severe hepatic impairment, and its use in this population is not recommended.
Missed Dose
If you miss a dose or vomit after taking Zejula, do not take an extra dose. Simply take your next dose at the normally scheduled time. Do not take a double dose to make up for a missed dose. If you frequently forget doses, discuss with your doctor or pharmacist about strategies to help you remember.
Overdose
If you take more than your normal dose of Zejula, contact your doctor immediately. There is no specific antidote for niraparib overdose. Treatment of overdose would be supportive and based on the symptoms experienced. In clinical trials, doses up to 900 mg daily were evaluated, with dose-dependent increases in hematologic toxicity being the primary concern.
What Are the Side Effects of Zejula?
Like all medicines, Zejula can cause side effects, although not everybody gets them. The side effects of Zejula are primarily related to its mechanism of action (affecting rapidly dividing cells, including blood-forming cells in the bone marrow) and its effects on blood pressure regulation. Most side effects are manageable through dose adjustments, treatment interruptions, and supportive care. Your healthcare team will monitor you closely, especially during the first few months of treatment.
Contact your doctor immediately if you experience: unusual bruising or prolonged bleeding (sign of low platelets), fever or signs of infection (sign of low white blood cells), severe fatigue with pale skin and rapid heartbeat (sign of severe anemia), sudden severe headache with visual changes or confusion (may indicate PRES or hypertensive crisis), or signs of a severe allergic reaction (swelling, rash, difficulty breathing).
Serious Side Effects
The following serious side effects require prompt medical attention. Your doctor has weighed the benefits of Zejula against the risks of these side effects, but it is important to recognize them early:
Very Common Serious Side Effects
May affect more than 1 in 10 patients
- Thrombocytopenia (low platelets) – bruising or bleeding that lasts longer than usual
- Anemia (low red blood cells) – shortness of breath, extreme tiredness, pale skin, or rapid heartbeat
- Neutropenia (low white blood cells) – increased risk of infection with fever, chills, weakness, or pain
- Leukopenia (decreased white blood cells in the blood)
Common Serious Side Effects
May affect up to 1 in 10 patients
- Allergic reactions (including severe, life-threatening reactions) – raised itchy rash (hives), swelling of face or mouth (angioedema), difficulty breathing
- MDS/AML (myelodysplastic syndrome or acute myeloid leukemia) – blood cancer arising from bone marrow problems
Uncommon Serious Side Effects
May affect up to 1 in 100 patients
- Febrile neutropenia – fever with low white blood cells
- Pancytopenia – simultaneous decrease in red blood cells, white blood cells, and platelets
Rare Serious Side Effects
May affect up to 1 in 1,000 patients
- Hypertensive crisis – sudden, severe blood pressure elevation that may cause organ damage or be life-threatening
- PRES (posterior reversible encephalopathy syndrome) – seizures, headache, confusion, and visual changes; a medical emergency
Other Side Effects
The following side effects are generally less serious but should be discussed with your doctor if they become troublesome or persistent:
Very Common
May affect more than 1 in 10 patients
- Nausea
- Fatigue and weakness
- Constipation
- Vomiting
- Abdominal pain
- Insomnia (difficulty sleeping)
- Headache
- Decreased appetite
- Runny or stuffy nose
- Diarrhea
- Shortness of breath
- Back pain
- Joint pain
- High blood pressure
- Indigestion (dyspepsia)
- Dizziness
- Cough
- Urinary tract infection
- Palpitations (feeling your heart beat irregularly or strongly)
Common
May affect up to 1 in 10 patients
- Photosensitivity (sunburn-like skin reactions after sun exposure)
- Swollen feet, ankles, legs, or hands (peripheral edema)
- Low potassium levels in the blood (hypokalemia)
- Bronchitis (inflammation of the airways)
- Abdominal bloating
- Anxiety and nervousness
- Depression
- Nosebleeds
- Weight loss
- Muscle pain
- Difficulty concentrating, memory problems (cognitive impairment)
- Red, inflamed eyes (conjunctivitis)
- Rapid heart rate (tachycardia)
- Dry mouth
- Mouth and gastrointestinal inflammation (stomatitis, mucositis)
- Skin rash
- Abnormal blood test values (elevated liver enzymes)
- Abnormal taste in the mouth (dysgeusia)
Uncommon
May affect up to 1 in 100 patients
- Confusion
- Non-infectious pneumonitis (lung inflammation causing breathlessness and breathing difficulties)
Many of the common side effects of Zejula can be managed effectively. Nausea, for example, often improves over time and can be reduced by taking Zejula at bedtime. Your doctor may also prescribe anti-nausea medications (antiemetics) to help manage this symptom. Fatigue is another common concern and may be addressed through activity planning, adequate rest, and nutritional support. Your healthcare team is experienced in managing these side effects and will work with you to optimize your quality of life during treatment.
It is important to report any suspected side effects to your healthcare provider. Reporting helps ensure continuous monitoring of the benefit-risk balance of Zejula. You can also report side effects directly to your national adverse drug reaction reporting system (e.g., FDA MedWatch in the US, Yellow Card Scheme in the UK, or EMA EudraVigilance in the EU).
How Should You Store Zejula?
Proper storage of Zejula is important to ensure the medication remains effective and safe to use throughout the treatment period. Follow these storage guidelines carefully:
- Temperature: No special temperature storage requirements. Store at room temperature.
- Packaging: Keep the tablets in the original blister packaging to protect them from moisture. Do not remove tablets from the blister until you are ready to take them.
- Expiration: Do not use Zejula after the expiration date printed on the carton and blister after “EXP.” The expiration date refers to the last day of the stated month.
- Children: Keep this medicine out of the sight and reach of children.
- Disposal: Do not throw away medicines via household waste or wastewater. Ask your pharmacist how to dispose of medicines you no longer use. These measures help to protect the environment.
Zejula 100 mg film-coated tablets are supplied in blister packs or child-resistant blister packs containing either 56 or 84 tablets per carton. Not all pack sizes may be marketed in all countries. The tablets are grey, oval, film-coated tablets debossed with “100” on one side and “Zejula” on the other side.
What Does Zejula Contain?
Each Zejula film-coated tablet contains niraparib tosylate monohydrate, equivalent to 100 mg of niraparib as the active substance. The following inactive ingredients (excipients) are included in the formulation:
Tablet core: Crospovidone, lactose monohydrate, magnesium stearate, microcrystalline cellulose (E 460), povidone (E 1201), colloidal hydrated silica.
Film coating: Polyvinyl alcohol (E 1203), titanium dioxide (E 171), macrogol (E 1521), talc (E 553b), black iron oxide (E 172).
This medicine contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, discuss this with your doctor before taking Zejula.
Zejula 100 mg tablets are grey, oval, film-coated tablets with “100” debossed on one side and “Zejula” on the other side. If your tablets look different from this description, do not take them and consult your pharmacist.
Frequently Asked Questions About Zejula
Zejula (niraparib) is a PARP inhibitor used as maintenance therapy for adult women with ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. It is prescribed after the cancer has responded to platinum-based chemotherapy, either as first-line maintenance therapy or after cancer recurrence. By blocking PARP enzymes that cancer cells need for DNA repair, Zejula causes these cells to accumulate lethal DNA damage, slowing or preventing cancer recurrence and prolonging the time before the disease progresses.
Zejula works by inhibiting PARP-1 and PARP-2 enzymes that are critical for DNA repair. When PARP is blocked, single-strand DNA breaks cannot be repaired and accumulate into double-strand breaks during cell division. In cancer cells with pre-existing DNA repair defects (such as BRCA mutations or homologous recombination deficiency), this leads to catastrophic genomic instability and cell death through a mechanism called synthetic lethality. Importantly, Zejula has shown efficacy in patients both with and without BRCA mutations.
The most common side effects include low blood counts (thrombocytopenia, anemia, neutropenia), nausea, fatigue, constipation, vomiting, abdominal pain, insomnia, headache, decreased appetite, and high blood pressure. Blood counts are monitored regularly. Your doctor may adjust the dose or temporarily pause treatment if blood counts become too low. Taking Zejula at bedtime and with a light meal can help reduce nausea.
No, Zejula should not be taken during pregnancy as it may harm the developing baby. Based on its mechanism of action (inhibiting DNA repair), niraparib is expected to cause fetal harm. Women of childbearing potential must use highly effective contraception during treatment and for 6 months after the last dose. A pregnancy test is required before starting treatment. Breastfeeding is also not allowed during treatment and for 1 month after the last dose.
For first-line maintenance, the starting dose is typically 200 mg (two 100 mg tablets) once daily. If you weigh 77 kg or more and have platelet counts of 150,000/µL or higher, the starting dose is 300 mg (three tablets) once daily. For recurrent ovarian cancer maintenance, the starting dose is 300 mg once daily. Zejula should be taken at the same time each day, preferably at bedtime to reduce nausea. Your doctor may reduce the dose if you experience significant side effects.
Yes, Zejula has demonstrated efficacy in patients both with and without BRCA mutations. In the PRIMA trial, niraparib significantly prolonged progression-free survival in the overall population, including patients without BRCA mutations. While patients with BRCA mutations or homologous recombination deficiency (HRD) tend to derive the greatest benefit, Zejula remains effective across the broader population of ovarian cancer patients, making it one of the most broadly applicable PARP inhibitors available.
References
- European Medicines Agency (EMA). Zejula (niraparib) – Summary of Product Characteristics. Last updated 2025. Available at: www.ema.europa.eu
- U.S. Food and Drug Administration (FDA). Zejula (niraparib) – Prescribing Information. Revised 2024. Available at: www.fda.gov
- González-Martín A, Pothuri B, Vergote I, et al. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer (PRIMA/ENGOT-OV26/GOG-3012). N Engl J Med. 2019;381(25):2391-2402. doi:10.1056/NEJMoa1910962
- Mirza MR, Monk BJ, Herrstedt J, et al. Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer (NOVA/ENGOT-OV16). N Engl J Med. 2016;375(22):2154-2164. doi:10.1056/NEJMoa1611310
- Colombo N, Sessa C, du Bois A, et al. ESMO-ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease. Ann Oncol. 2019;30(5):672-705. doi:10.1093/annonc/mdz062
- National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Ovarian Cancer Including Fallopian Tube Cancer and Primary Peritoneal Cancer. Version 1.2024.
- Lord CJ, Ashworth A. PARP inhibitors: Synthetic lethality in the clinic. Science. 2017;355(6330):1152-1158. doi:10.1126/science.aam7344
- World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd List, 2023. Geneva: World Health Organization; 2023.
Editorial Team
Medical Content
Written by iMedic Medical Editorial Team – Specialists in Oncology and Clinical Pharmacology
Medical Review
Reviewed by iMedic Medical Review Board according to EMA, FDA, ESMO, and NCCN guidelines
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Level 1A – Based on systematic reviews and meta-analyses of randomized controlled trials (PRIMA, NOVA)
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Last medical review: . This content is reviewed and updated regularly to reflect the latest medical evidence and guidelines.