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Niraparib

Medically reviewed by Drugs.com. Last updated on Aug 17, 2020.

Pronunciation

(nye RAP a rib)

Index Terms

  • MK4827
  • Niraparib Tosylate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral, as tosylate:

Zejula: 100 mg [contains brilliant blue fcf (fd&c blue #1), tartrazine (fd&c yellow #5)]

Brand Names: U.S.

  • Zejula

Pharmacologic Category

  • Antineoplastic Agent, PARP Inhibitor

Pharmacology

Niraparib is a poly (ADP-ribose) polymerase (PARP) enzyme inhibitor, which is highly selective for PARP-1 and PARP-2. PARP-1 and PARP-2 are involved in detecting DNA damage and promote repair (Mirza 2016). Inhibiting PARP enzymatic activity results in DNA damage, apoptosis and cell death. Niraparib induces cytotoxicity in tumor cell lines with and without BRCA1/2 deficiencies.

Distribution

Vd/F: 1,074 L

Metabolism

Metabolized by carboxylesterases to an inactive metabolite, which subsequently undergoes glucuronidation.

Excretion

Urine (~48% [at 21 days]; 11% [pooled samples collected over 6 days] as unchanged drug); Feces (~39% [at 21 days]; 19% [pooled samples collected over 6 days] as unchanged drug)

Time to Peak

Within 3 hours

Half-Life Elimination

36 hours

Protein Binding

83%

Use: Labeled Indications

Ovarian, fallopian tube, or primary peritoneal cancer:

First-line maintenance treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer in adults who are in a complete or partial response to first-line platinum-based chemotherapy.

Maintenance treatment of recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in adults who are in a complete or partial response to platinum-based chemotherapy.

Treatment of advanced ovarian, fallopian tube, or primary peritoneal cancer in adults who have been treated with ≥3 prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency positive status, defined by either a deleterious or suspected deleterious BRCA mutation or genomic instability and progression >6 months after response to the last platinum-based chemotherapy. Select patients for therapy based on an approved companion diagnostic for niraparib.

Contraindications

There are no contraindications listed in the manufacturer's US labeling.

Canadian labeling: Hypersensitivity to niraparib or any component of the formulation; breastfeeding.

Dosing: Adult

Note: Niraparib is associated with a moderate emetic potential; antiemetics may be necessary to prevent nausea and vomiting.

Ovarian, fallopian tube, or primary peritoneal cancer, advanced (first-line maintenance treatment): Begin niraparib no later than 12 weeks following the most recent platinum-containing regimen; continue until disease progression or unacceptable toxicity (González-Martin 2019).

Oral:

Patients <77 kg or with a platelet count <150,000/mm3: 200 mg once daily.

Patients ≥77 kg and with a platelet count ≥150,000/mm3: 300 mg once daily.

Ovarian, fallopian tube, or primary peritoneal cancer, advanced (after ≥3 chemotherapy regimens): Note: Select patients for niraparib therapy based on homologous recombination deficiency positive status, as defined by either deleterious or suspected deleterious BRCA mutation and/or genomic instability score.

Oral: 300 mg once daily, continue until disease progression or unacceptable toxicity (Moore 2019).

Ovarian, fallopian tube, or primary peritoneal cancer, recurrent (maintenance treatment):

Oral: 300 mg once daily, continue until disease progression or unacceptable toxicity (Mirza 2016). Begin niraparib no later than 8 weeks following the most recent platinum-containing regimen.

Reduced initial dosing strategy (off label): Oral: Patients weighing <77 kg and/or with baseline platelets <150,000/mm3: Initial: 200 mg once daily (Berek 2018; Moore 2018). After 2 to 3 months, in the absence of hematologic toxicity, may consider escalation to usual dose of 300 mg once daily (Moore 2018).

Missed/vomited doses: If a dose is missed or vomited, an additional dose should not be taken that day. Resume dosing with the next scheduled daily dose.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Adjustment for Toxicity

Adverse reactions may be managed with treatment interruption, dose reduction, and/or discontinuation.

Niraparib Recommended Dosage Reduction Levels

Starting (initial) dose level

200 mg once daily

300 mg once daily

aIf further dose reduction below 100 mg once daily is necessary, discontinue niraparib.

First dose reduction

100 mg once dailya

200 mg once daily

Second dose reduction

Discontinue niraparib

100 mg once dailya

Hematologic toxicity:

Platelets <100,000/mm3:

First occurrence: Withhold niraparib for a maximum of 28 days and monitor blood counts weekly. When platelets are ≥100,000/mm3, resume niraparib at the same or at a reduced dose. If platelet count was <75,000/mm3, resume at a reduced dose.

Second occurrence: Withhold niraparib for a maximum of 28 days and monitor blood counts weekly. When platelets are ≥100,000/mm3, resume niraparib at a reduced dose. Discontinue if platelet count has not returned to acceptable levels within 28 days of interrupting dose, or if dose has already been reduced to 100 mg once daily.

Neutrophils <1,000/mm3 or hemoglobin <8 g/dL: Withhold niraparib for a maximum of 28 days and monitor blood counts weekly. When neutrophils are ≥1,500/mm3 or hemoglobin is ≥9 g/dL, resume niraparib at a reduced dose. Discontinue if neutrophils and/or hemoglobin have not returned to acceptable levels within 28 days of interrupting dose, or if dose has already been reduced to 100 mg once daily.

Hematologic toxicity requiring transfusion: Withhold niraparib. Consider platelet transfusion for platelets ≤10,000/mm3. If other risk factors (eg, concurrent anticoagulation or antiplatelet therapy), consider interrupting the anticoagulant/antiplatelet and/or transfusing to a higher platelet count. Resume niraparib at a reduced dose.

Secondary myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML): Discontinue niraparib with confirmed diagnosis of MDS or AML.

Nonhematologic toxicity:

Grade 3 or higher adverse reaction (where prophylactic management is not feasible or persistent despite management): Withhold niraparib for a maximum of 28 days or until resolution; resume with the dose reduced.

Grade 3 or higher adverse reaction lasting >28 days at a dose of 100 mg once daily: Discontinue niraparib.

Administration

Oral: Administer at approximately the same time each day, either with or without food. Swallow capsules whole; do not chew, crush, or split. Niraparib is associated with a moderate emetic potential; antiemetics may be necessary to prevent nausea and vomiting. Consider administering at bedtime to diminish the potential for nausea and vomiting.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F).

Drug Interactions

Baricitinib: Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted. Consider therapy modification

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy

Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Consider therapy modification

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Management: Consider avoiding Echinacea in patients receiving therapeutic immunosuppressants. If coadministered, monitor for reduced efficacy of the immunosuppressant during concomitant use. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Inebilizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Management: Avoid use of immunosuppressants (including systemic corticosteroids) prior to initiation of nivolumab. Use of immunosuppressants after administration of nivolumab (eg, for immune-related toxicity) is unlikely to affect nivolumab efficacy. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Ozanimod: Immunosuppressants may enhance the immunosuppressive effect of Ozanimod. Monitor therapy

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Management: Consider avoiding concomitant use of roflumilast and immunosuppressants as recommended by the Canadian product monograph. Inhaled or short-term corticosteroids are unlikely to be problematic. Consider therapy modification

Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification

Smallpox and Monkeypox Vaccine (Live): Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). Monitor therapy

Solriamfetol: May enhance the hypertensive effect of Hypertension-Associated Agents. Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification

Upadacitinib: Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib. Management: Concomitant use of upadacitinib with potent immunosuppressants is not recommended. Drugs listed as exceptions to this monograph are discussed in separate drug interaction monographs. Avoid combination

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: Smallpox and Monkeypox Vaccine (Live). Avoid combination

Adverse Reactions

>10%:

Cardiovascular: Hypertension (18% to 20%)

Dermatologic: Skin rash (21%)

Endocrine: Decreased serum magnesium (36%), increased serum glucose (66%)

Gastrointestinal: Constipation (40%), decreased appetite (19% to 25%), dyspepsia (18%), nausea (57% to 74%), stomatitis (20%), vomiting (22% to 34%)

Genitourinary: Urinary tract infection (13%)

Hematologic & oncologic: Anemia (50% to 64%; grades 3/4: 25% to 31%), leukopenia (17% to 28%; grades 3/4: 5%), lymphocytopenia (51%; grades 3/4: 7%), neutropenia (30% to 42%; grades 3/4: 20% to 21%), thrombocytopenia (61% to 66%; grades 3/4: 29% to 39%)

Hepatic: Increased serum alanine aminotransferase (≤29%), increased serum alkaline phosphatase (46%), increased serum aspartate aminotransferase (≤36%)

Nervous system: Anxiety (11%), dizziness (18% to 19%), fatigue (≤57%), headache (26%), insomnia (25% to 27%)

Neuromuscular & skeletal: Asthenia (≤57%), back pain (18%), musculoskeletal pain (39%)

Renal: Acute renal failure (12%), increased serum creatinine (40%)

Respiratory: Cough (16% to 18%), dyspnea (20% to 22%), nasopharyngitis (23%)

1% to 10%:

Cardiovascular: Palpitations (10%), peripheral edema, tachycardia

Endocrine & metabolic: Hypokalemia, increased gamma-glutamyl transferase, weight loss

Gastrointestinal: Dysgeusia (10%), intestinal obstruction (small intestinal obstruction: 3%), xerostomia (10%)

Nervous system: Depression

Ophthalmic: Conjunctivitis

Respiratory: Bronchitis, epistaxis

<1%: Hematologic & oncologic: Acute myelocytic leukemia, myelodysplastic syndrome

Postmarketing:

Cardiovascular: Hypertensive crisis

Dermatologic: Skin photosensitivity

Hypersensitivity: Anaphylaxis, hypersensitivity reaction

Nervous system: Cognitive dysfunction, confusion, disorientation, hallucination, reversible posterior leukoencephalopathy syndrome

Respiratory: Pneumonia

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Thrombocytopenia, anemia, and neutropenia commonly occur, including grade 3 and 4 events. Monitor blood counts weekly for the first month, then monthly for 11 months, then periodically thereafter. Do not initiate niraparib until hematologic toxicity due to previous chemotherapy has resolved to grade 1 or lower. Hematologic toxicity may require treatment interruption, dose reduction, and/or discontinuation. If hematologic toxicities do not resolve within 28 days following interruption, discontinue niraparib and obtain consult with hematology for further assessment, including marrow and cytogenetic analysis. In patients with low body weight (<77 kg) and/or low baseline platelets (<150,000/mm3), an initial reduced dosing strategy is suggested to reduce hematologic toxicity while maintaining efficacy (Berek 2018; González-Martin 2019; Moore 2018).

• Cardiovascular effects: Hypertension and hypertensive crisis have been reported, including grade 3 and 4 hypertension (hypertension required discontinuation in rare cases). The median time from the first niraparib dose to hypertension onset was 15 to 77 days (range: 1 to 531 days). The median duration of hypertension was 7 to 15 days (range: 1 to 118 days). Monitor BP and heart rate at least weekly for the first 2 months of therapy, then monthly for the first year and periodically thereafter. Patients with cardiac disorders (especially coronary insufficiency, arrhythmias, and hypertension) should be monitored closely. If necessary, hypertension should be managed with antihypertensives and niraparib dose adjustment.

• GI toxicity: Niraparib is associated with a moderate emetic potential; antiemetics may be necessary to prevent nausea and vomiting. Consider administering niraparib at bedtime to diminish the potential for nausea and vomiting. Nausea, vomiting, constipation, and mucositis/stomatitis have been reported.

• Secondary malignancy: Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) have been reported (rare), including fatal cases. The duration of niraparib treatment prior to the development of MDS/AML varied from <1 month to ~5 years. All patients had received prior chemotherapy with platinum-based regimens and/or other DNA-damaging agents, including radiotherapy. Discontinue niraparib if MDS/AML is confirmed.

Dosage form specific issues:

• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007). See manufacturer’s labeling.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Homologous recombination deficiency status: Select patients for the treatment of advanced ovarian cancer (after ≥3 prior chemotherapy regimens) based on the presence of homologous recombination deficiency positive status, as defined by either deleterious or suspected deleterious BRCA mutation, or genomic instability and progression >6 months after response to the last platinum-based chemotherapy. Select patients for therapy based on an approved companion diagnostic for niraparib. Information on approved diagnostic tests may be found at http://www.fda.gov/companiondiagnostics.

Monitoring Parameters

Homologous recombination deficiency status in patients with advanced ovarian cancer (after ≥3 prior chemotherapy regimens); CBC with differential (weekly for the first month, then monthly for 11 months, then periodically); evaluate pregnancy status prior to treatment (in females of reproductive potential). Monitor BP and heart rate at least weekly for the first 2 months, then monthly for the first year and periodically thereafter. Monitor adherence.

Reproductive Considerations

Pregnancy testing should be conducted prior to treatment and effective contraception should be used during therapy and for at least 6 months after the last niraparib dose in females of reproductive potential.

Pregnancy Considerations

Animal reproduction studies have not been conducted, however based on the mechanism of action, niraparib may cause fetal harm if used during pregnancy.

Patient Education

What is this drug used for?

• It is used to treat ovarian, fallopian tube, or peritoneal cancer.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Back pain

• Upset stomach

• Throwing up

• Constipation

• Diarrhea

• Stomach pain

• Heartburn

• Change in taste

• Trouble sleeping

• Anxiety

• Nose irritation

• Throat irritation

• Mouth irritation

• Mouth sores

• Dry mouth

• Not hungry

• Feeling tired or weak

• Muscle pain

• Joint pain

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Infection

• High blood sugar like confusion, feeling tired, more thirst, more hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit

• Urinary tract infection like blood in the urine, burning or painful urination, passing a lot of urine, fever, lower stomach pain, or pelvic pain

• Bleeding like throwing up blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding

• Electrolyte problems like mood changes, confusion, muscle pain or weakness, abnormal heartbeat, seizures, not hungry, or severe upset stomach or throwing up

• Kidney problems like not able to pass urine, blood in your urine, change in amount of urine passed, or weight gain

• Severe headache

• Severe dizziness

• Passing out

• Vision changes

• Weight loss

• Abnormal heartbeat

• Swelling of belly

• Shortness of breath

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.