(nye RAP a rib)
- Niraparib Tosylate
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral, as tosylate:
Zejula: 100 mg [contains fd&c blue #1 aluminum lake, fd&c yellow #5 aluminum lake]
Brand Names: U.S.
- Antineoplastic Agent, PARP Inhibitor
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.
Vd/F: 1,074 L
Metabolized by carboxylesterases to an inactive metabolite, which subsequently undergoes glucuronidation.
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
Use: Labeled Indications
Ovarian, fallopian tube, or primary peritoneal cancer: Maintenance treatment of recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who are in a complete or partial response to platinum-based chemotherapy.
There are no contraindications listed in the manufacturer's labeling.
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 treatment no later than 8 weeks following the most recent platinum-containing regimen.
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.
Refer to adult dosing.
Dosing: Renal Impairment
Renal function estimated using the Cockcroft-Gault formula.
CrCl 30 to <90 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
End stage renal disease (ESRD): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Dosing: Hepatic Impairment
Hepatic function estimated using the National Cancer Institute Organ Dysfunction Working Group Criteria.
Mild impairment: No dosage adjustment necessary.
Moderate to severe impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Dosing: Adjustment for Toxicity
Adverse reactions may be managed with treatment interruption, dose reduction, or discontinuation.
Recommended niraparib dosage adjustment levels:
Starting dose: 300 mg/day
First dose reduction: Reduce to 200 mg/day.
Second dose reduction: Reduce to 100 mg/day.
If further dose reduction below 100 mg/day is needed, discontinue niraparib.
First occurrence: Withhold treatment 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 treatment 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/day.
Neutrophils <1,000/mm3 or hemoglobin <8 g/dL: Withhold treatment 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/day.
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.
Grade 3 or higher adverse reaction (where prophylactic management is not feasible or persistent despite management): Withhold niraparib for up to 28 days or until resolution; may resume with the dose reduced (up to two dose reductions are permitted).
Grade 3 or higher adverse reaction lasting more than 28 days at a dose of 100 mg/day: Discontinue treatment.
Administer at approximately the same time each day, either with or without food. Swallow capsules whole. Consider administering at bedtime to diminish the potential for nausea and vomiting.
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).
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
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy
Cardiovascular: Hypertension (20%)
Central nervous system: Fatigue (≤57%), insomnia (27%), headache (26%), dizziness (18%), anxiety (11%)
Dermatologic: Skin rash (21%)
Gastrointestinal: Nausea (74%), constipation (40%), vomiting (34%), decreased appetite (25%), mucositis (≤20%), stomatitis (≤20%), dyspepsia (18%)
Genitourinary: Urinary tract infection (13%)
Hematologic & oncologic: Thrombocytopenia (61%; grades 3/4: 29%), anemia (50%; grades 3/4: 25%), neutropenia (30%; grades 3/4: 20%), leukopenia (17%; grades 3/4: 5%)
Hepatic: Increased serum AST (≤10% to 36%), increased serum ALT (≤10% to 28%)
Neuromuscular & skeletal: Weakness (≤57%), back pain (18%)
Respiratory: Nasopharyngitis (23%), dyspnea (20%), cough (16%)
1% to 10%:
Cardiovascular: Palpitations (10%), peripheral edema, tachycardia
Central nervous system: Depression
Endocrine & metabolic: Hypokalemia, increased gamma-glutamyl transferase, weight loss
Gastrointestinal: Dysgeusia (10%), xerostomia (10%)
Hepatic: Increased serum alkaline phosphatase
Renal: Increased serum creatinine
Respiratory: Bronchitis, epistaxis
<1%, postmarketing, and/or case reports: Acute myelocytic leukemia, hypertensive crisis, myelodysplastic syndrome
Concerns related to adverse effects:
• Bone marrow suppression: Thrombocytopenia, anemia and neutropenia commonly occur, including grade 3 and 4 events (which rarely required discontinuation). 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, or discontinuation. If hematologic toxicities do not resolve with 28 days following interruption, discontinue niraparib and obtain consult with hematology for further assessment, including marrow and cytogenetic analysis.
• Cardiovascular effects: Hypertension and hypertensive crisis have been reported, including grade 3 and 4 hypertension (hypertension required discontinuation in rare cases). Monitor blood pressure and heart rate monthly during 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.
• Gastrointestinal toxicity: Nausea, vomiting, constipation and mucositis/stomatitis have been reported. Consider administering niraparib at bedtime to diminish the potential for nausea and vomiting.
• 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 2 years. All patients had received prior chemotherapy, including platinum-based regimens. Discontinue niraparib if MDS/AML is confirmed.
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.
CBC with differential (weekly for the first month, then monthly for 11 months, then periodically); pregnancy test (prior to treatment; in females of reproductive potential). Monitor blood pressure and heart rate monthly during the first year and periodically thereafter.
Animal reproduction studies have not been conducted, however based on the mechanism of action, niraparib may cause fetal harm if used during pregnancy. 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 dose in women of reproductive potential. Fertility may be impaired if administered to males.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience back pain, nausea, vomiting, constipation, diarrhea, abdominal pain, heartburn, change in taste, insomnia, anxiety, rhinitis, pharyngitis, mouth irritation, mouth sores, dry mouth, lack of appetite, muscle pain, or joint pain. Have patient report immediately to prescriber signs of infection, signs of a urinary tract infection (hematuria, burning or painful urination, polyuria, fever, lower abdominal pain, or pelvic pain), signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; 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), severe headache, severe dizziness, passing out, vision changes, weight loss, abnormal heartbeat, abdominal edema, shortness of breath, or severe loss of strength and energy (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
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