Dosing & Uses
Dosage Forms & Strengths
capsule
- 100mg
Ovarian Cancer
Recurrent ovarian 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
- Start treatment no later than 8 weeks after their most recent platinum-containing regimen
- 300 mg PO qDay
- Continue until disease progression or unacceptable toxicity
Advanced ovarian cancer
First-line maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy
Start treatment no later than 12 weeks after their most recent platinum-containing regimen
<77 kg (170 lbs) OR with a platelet count <150,000/μL: 200 mg PO qDay
≥77 kg AND who have a platelet count ≥150,000/μL: 300 mg PO qDay
Continue until disease progression or unacceptable toxicity
Dosage Modifications
Dose reductions
-
300 mg starting dose
- First dose reduction: 200 mg/day
- Second dose reduction: 100 mg/day
- Discontinue if further dose reduction <100 mg/day required
-
200 mg starting dose
- First dose reduction: 100 mg/day
- Discontinue if further dose reduction <100 mg/day required
Nonhematologic adverse reactions
-
Persistent Grade ≥3 despite medical management
- Withhold for a maximum of 28 days or until adverse reaction resolves
- Resume at reduced dose level
-
Grade ≥3 reactions lasting >28 days and taking niraparib 100 mg/day
- Discontinue treatment
Hematologic adverse reactions
-
Platelet count <1000,000/mcL
- First occurrence: Withhold up to 28 days and monitor blood cell counts weekly until platelets ≥100,000/mcL; resume at same or reduced dose; if platelet count is <75,000/mcL, resume at reduced dose
- Second occurrence: Withhold up to 28 days and monitor blood cell counts weekly until platelets ≥100,000/mcL; resume at reduced dose; discontinue if platelet count has not returned to acceptable levels within 28 days or if the patient is already on 100 mg/day
-
Neutrophil count <1000/mcL or hemoglobin <8 g/dL
- Withhold up to 28 days and monitor blood cell counts weekly until neutrophils ≥1500/mcL or hemoglobin ≥9 g/dL; resume at reduced dose
- Discontinue if neutrophils and/or hemoglobin have not returned to acceptable levels within 28 days or if the patient is already on 100 mg/day
-
Hematologic adverse reaction requiring transfusion
- Platelet count ≤10,000/mcL: Consider platelet transfusion
- If other risk factors exist (eg anticoagulants, antiplatelets), consider interrupting anticoagulants or antiplatelet drugs and/or transfuse at a higher platelet count
- Resume at a reduced dose
Renal impairment
- Mild-to-moderate (CrCl ≥30 mL/min): No dose adjustment required
- Severe or ESRD: Not studied
Hepatic impairment
- Mild (total bilirubin [TB] <1.5x ULN and any AST level): No dosage adjustment necessary
- Moderate [TB 1.5x-3x ULN and any AST): Reduce starting dose to 200 mg PO qDay
- Severe [TB >3x ULN and any AST): Not established
Dosing Considerations
Patient selection
- For maintenance treatment of recurrent ovarian cancer
- Select based on deleterious or suspected deleterious BRCA mutation
- Information on FDA-approved tests is available at: http://www.fda.gov/CompanionDiagnostics
Safety and efficacy not established
Adverse Effects
Adverse effects include all grades unless otherwise stated
>10%
Nausea (74%)
Thrombocytopenia (61%)
Fatigue/asthenia (57%)
Fatigue (55%)
Anemia (50%)
Constipation (40%)
Musculoskeletal pain (36%)
Vomiting (34%)
Abdominal pain/distention (33%)
Neutropenia (30%)
Thrombocytopenia, grades 3 or 4 (29%)
Insomnia (27%)
Headache (26%)
Anemia, grades 3 or 4 (25%)
Decreased appetite (24%)
Nasopharyngitis (23%)
Rash (21%)
Hypertension (20%)
Neutropenia, grades 3 or 4 (20%)
Mucositis/stomatitis (20%)
Diarrhea (20%)
Dyspepsia (20%)
Myalgia (19%)
Back pain (18%)
Dyspepsia (18%)
Dizziness (18%)
Leukopenia (17%)
Cough (16%)
Acute kidney injury (13%)
UTI (13%)
Arthralgia (13%)
Anxiety (11%)
Hypomagnesemia (11%)
1-10%
Palpitations (10%)
Dry mouth (10%)
AST/ALT elevation (10%)
Dysgeusia (10%)
Hypertension, grade 3 or 4 (9%)
Leukopenia, grades 3 or 4 (5%)
Postmarketing Reports
Immune system disorders: Hypersensitivity (including anaphylaxis)
Nervous system disorders: Posterior reversible encephalopathy syndrome (PRES)
Psychiatric disorders: Confusional state/disorientation, hallucination, cognitive impairment (eg, memory impairment, concentration impairment)
Respiratory, thoracic, and mediastinal disorders: Non-infectious pneumonitis
Skin and SC tissue disorders: Photosensitivity
Hematologic disorders: Neutropenic infection, neutropenic sepsis, febrile neutropenia, pancytopenia
Vascular disorders: Hypertensive crisis
Warnings
Contraindications
None
Cautions
Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), including cases with fatal outcome, reported; for suspected MDS/AML or prolonged hematological toxicities, refer the patient to a hematologist for further evaluation; discontinue drug if MDS/AML confirmed
Hypertension and hypertensive crisis reported; monitor BP and HR monthly for the first year and periodically thereafter during treatment; medically manage hypertension with antihypertensive medications and niraparib dose adjustment
Capsules contain FD&C Yellow No. 5 (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons; incidence of sensitivity in the general population is low, frequently seen in patients who also have aspirin hypersensitivity
Based on its mechanism of action, can cause fetal harm if administered to a pregnant woman (see Pregnancy)
Encephalopathy syndrome
- Posterior reversible encephalopathy syndrome (PRES) reported; signs and symptoms of PRES include seizure, headache, altered mental status, visual disturbance, or cortical blindness, with or without associated hypertension
- A diagnosis of PRES requires confirmation by brain imaging, preferably magnetic resonance imaging
- Monitor all patients receiving treatment for signs and symptoms of PRES; if PRES is suspected, promptly discontinue drug and administer appropriate treatment
- The safety of reinitiating treatment in patients previously experiencing PRES not known
Bone marrow suppression
- May cause bone marrow suppression resulting in hematologic toxicities (eg, thrombocytopenia, anemia, neutropenia)
- Do not initiate until patients have recovered from hematological toxicities caused by previous chemotherapy (grade ≤1)
- Monitor complete blood cell counts weekly for the first month, monthly for the next 11 months of treatment, and periodically after this time (also see Dosage Modifications)
Pregnancy
Pregnancy
Niraparib has the potential to cause teratogenicity and/or embryo-fetal death since niraparib is genotoxic and targets actively dividing cells in animals and patients (eg, bone marrow)
A pregnancy test is recommended for females of reproductive potential prior to initiating drug
Based on animal studies, may impair fertility in males of reproductive potential
Contraception
- Advise females of reproductive potential to use effective contraception during treatment for at least 6 months following the last dose
Lactation
No data are available regarding the presence of niraparib or its metabolites in human milk, or on its effects on the breastfed infant or milk production
Owing to the potential for serious adverse reactions in breastfed infants, advise a lactating woman not to breastfeed during treatment and for 1 month after receiving the final dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Poly (ADP-ribose) polymerase (PARP) inhibitor; niraparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes, resulting in DNA damage, apoptosis, and cell death
Absorption
Bioavailability: 73%
Peak plasma time: 3 hr
Peak plasma concentration: 804 ng/mL
Distribution
Protein bound: 83%
Vd: 1200 L
Metabolism
Metabolized primarily by carboxylesterases (CEs) to form a major inactive metabolite, which subsequently undergoes glucuronidation
Elimination
Half-life: 36 hr
Excretion: 47.5% urine; 38.8% feces
Administration
Oral Administration
May take with or without food
Take dose at about the same time each day
Swallow each capsule whole
Bedtime administration may be a potential method for managing nausea
Missed or vomited dose
- Take next dose at its regularly scheduled time
- Do not take an additional dose
Storage
Store at 20-25°C (68-77°F); excursions are permitted between 15-30°C (59-86°F)
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Zejula oral - | 100 mg capsule |  |
Copyright © 2010 First DataBank, Inc.
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