Niraparib tosylate, an inhibitor of poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP), is an antineoplastic agent.1
Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Niraparib is used as first-line maintenance therapy for the treatment of adults with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD)-positive status defined by the presence of either a deleterious or suspected deleterious BRCA mutation and/or genomic instability.1
Niraparib is also used as maintenance therapy for the treatment of adults with deleterious or suspected deleterious germline BRCA -mutated recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.1
Patients should be selected for niraparib therapy based on an FDA-authorized companion diagnostic.1
The drug has been designated an orphan drug by FDA for the treatment of ovarian cancer.3
Niraparib was previously indicated, based on the QUADRA study, for the treatment of adults with HRD-positive advanced ovarian, fallopian tube, or primary peritoneal cancer previously treated with 3 or more chemotherapy regimens;1, 14 however, the manufacturer voluntarily withdrew this indication in September 2022 based on the totality of information from PARP inhibitors in the late line treatment setting in ovarian cancer.16 A potential detrimental effect on overall survival was observed with other PARP inhibitors in 2 independent randomized, active-controlled clinical trials conducted in a BRCA mutant 3L+ advanced ovarian cancer population.16 .1
First-line Maintenance Treatment of HRD-positive Advanced Ovarian Cancer
In the PRIMA study, 733 patients with stage 3 or 4 high grade serous or endometrioid tumors were randomized in a 2:1 ratio to receive niraparib or placebo within 12 weeks of the last dose of platinum-based chemotherapy.1, 9 In the initial trial protocol, niraparib was given at a dosage of 300 mg once daily; however, the trial protocol was amended when predictive modeling of the NOVA study indicated that patients with a body weight less than 77 kg or platelet count less than 150,000/mm3 should receive an initial niraparib dosage of 200 mg once daily and those with a body weight of 77 kg or greater and platelet count of 150,000/mm3 or greater should receive an initial niraparib dosage of 300 mg once daily.1, 9, 15 Approximately 35% of patients enrolled in the study received an initial niraparib dosage of 200 or 300 mg according to baseline body weight and platelet count.1 Treatment cycles were repeated every 28 days and continued for 36 months or until disease progression occurred.9 Patients randomized to receive placebo were not permitted to cross over to niraparib therapy upon disease progression.9 Patients were stratified by best response during the front-line platinum-based regimen, neoadjuvant chemotherapy, and homologous recombination deficiency (HRD) status.1, 9
The primary endpoint of the PRIMA study was progression-free survival as assessed by a blinded independent central review (BICR) committee according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and, in some cases, additional criteria (e.g., increasing serum cancer antigen-125 [CA-125] concentration, clinical signs and symptoms) were applied.1, 9 In the overall study population, the median age of patients was 62 years; 89% of patients were white, 71% had a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 0, 65% had stage III disease, 67% had received neoadjuvant chemotherapy, and 69% had a complete response to first-line platinum-based chemotherapy.1 Approximately one-half of patients enrolled in the study were HRD-positive (defined as the presence of a BRCA mutation and/or a genomic instability score of 42 or greater as determined by the Myriad myChoice CDx assay).1, 9
Patients receiving niraparib had a substantially longer median progression-free survival than those receiving placebo in the HRD-positive cohort (21.9 versus 10.4 months; hazard ratio: 0.43; 95% confidence interval, 0.31-0.59) and overall study population (13.8 versus 8.2 months; hazard ratio: 0.62; 95% confidence interval, 0.50-0.76).1, 9 Results of subgroup analyses (based on response to platinum-based chemotherapy, receipt of neoadjuvant chemotherapy, and presence/absence of BRCA mutation or HRD) suggested that the effect of niraparib on progression-free survival was generally consistent across subgroups.1, 9 In an exploratory analysis of patients who received a weight- and platelet count-based starting dosage of niraparib, the hazard ratio for progression-free survival was 0.39 (95% confidence interval of 0.22-0.72) in the HRD cohort and 0.68 (95% confidence interval of 0.48-0.97) in the overall study population.1 At the time of analysis, overall survival data were immature; however, estimated overall survival at 24 months was 84% in patients receiving niraparib compared with 77% in those receiving placebo (hazard ratio: 0.70; 95% confidence interval, 0.44-1.11) in the overall study population and 91 or 85% (hazard ratio: 0.61; 95% confidence interval, 0.27-1.39), respectively, in the HRD-positive cohort.9
Maintenance Treatment of Platinum-sensitive Germline BRCA -mutated Recurrent Ovarian Cancer
The initial approved indication for niraparib as maintenance therapy for adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in complete or partial response following platinum-based chemotherapy was based principally on the results of a randomized, double-blind, placebo-controlled phase 3 study (NOVA).1, 2 Patients in the NOVA study were enrolled into 1 of 2 cohorts based on BRCA mutation status (confirmed or suspected deleterious); those with germline BRCA mutations were assigned to the germline BRCA -mutated (g BRCA -mutation) cohort and those without germline BRCA mutations were assigned to the non-g BRCA -mutation cohort (including those with wild-type g BRCA using the BRACAnalysis CDx diagnostic test).1, 2 The non-g BRCA -mutation cohort included patients with HRD-positive tumors, including those with somatic BRCA mutations and other defects, as well as patients with HRD-negative tumors.2
In the NOVA study, 553 patients were randomized in a 2:1 ratio to receive either niraparib (300 mg once daily) or placebo within 8 weeks following the last dose of platinum-based chemotherapy.1, 2 Treatment was continued until disease progression or unacceptable toxicity occurred or the patient withdrew from the study.2 Patients randomized to receive placebo were not permitted to cross over to niraparib therapy upon disease progression.2 Patients were stratified according to time to progression following the penultimate platinum-based regimen, concomitant use of bevacizumab with the penultimate or last platinum-based regimen, and best response following the most recent platinum-based regimen.1
The primary end point of the NOVA study was progression-free survival as assessed by a BICR according to RECIST v1.1 and, in some cases, additional criteria (e.g., increasing serum CA-125 concentrations, clinical signs and symptoms) were considered.1, 2, 4 The median age of patients ranged from 57-64 years in those receiving niraparib and 58-67 years in those receiving placebo; 86% of all patients were White and 67 and 69% of patients in the niraparib and placebo groups, respectively, had a baseline ECOG performance status of 0.1, 2 All enrolled patients had previously received at least 2 platinum-based regimens; approximately 40% of all patients had received 3 or more previous lines of therapy, 26% of the niraparib-treated patients had previously received bevacizumab therapy, 51% of all patients were in complete response following platinum-based chemotherapy, and 6-12 months had elapsed since penultimate platinum-based chemotherapy in 39% of patients in both the niraparib and placebo groups.1, 2 In the initial NOVA analysis, patients receiving niraparib had a substantially longer median progression-free survival than those receiving placebo in both the g BRCA -mutation (21 versus 5.5 months; hazard ratio: 0.26) and non-g BRCA -mutation cohorts (9.3 versus 3.9 months; hazard ratio: 0.45).1 Median progression-free survival also was significantly longer in niraparib-treated patients with HRD-positive epithelial ovarian, fallopian tube, or primary peritoneal cancer in the non-g BRCA -mutation cohort compared with those receiving placebo (12.9 versus 3.8 months; hazard ratio: 0.38).1, 2 A subgroup analysis of patients 70 years of age or older suggested that progression-free survival benefit and the incidence of adverse effects in patients receiving niraparib were comparable to those observed in younger adults.10 In a post-hoc analysis, significant progression-free survival benefit was observed regardless of the best response to the last platinum-based chemotherapy in patients receiving niraparib compared with those receiving placebo.11 At the time of the progression-free survival analysis, limited overall survival data were available; deaths were reported in 17% of patients across the 2 cohorts.1
In 2022, an FDA review of the final overall survival analysis of the NOVA trial revealed that, in the non- gBRCA -mutation cohort only, median overall survival (a secondary endpoint) was substantially reduced among patients administered niraparib versus those administered placebo (31 versus 35.8 months; hazard ratio: 1.06).32 This resulted in the FDA requesting restriction of the second-line maintenance indication for niraparib to only the patient population with deleterious or suspected gBRCA mutations.32
In a long-term safety analysis, hematologic adverse events generally decreased in incidence over time, with dosage reductions due to hematologic adverse events occurring most frequently during the first 3 months of niraparib therapy.13 Quality of life (measured with the Functional Assessment of Cancer Therapy-Ovarian Symptoms Index [FOSI], European quality of life (QOL) five-dimension five-level questionnaire [EQ-5D-5L], and European QOL-visual analog scale [EQ-VAS]) did not change substantially from baseline during the maintenance period, and were similar between both treatment groups.12
Newly Diagnosed Ovarian Cancer
Substantial progression-free survival benefit has been observed in patients with newly diagnosed advanced ovarian cancer who have achieved complete or partial response to first-line platinum-based chemotherapy receiving maintenance therapy with a PARP inhibitor.31
The American Society of Clinical Oncology (ASCO) recommends that olaparib, niraparib, or rucaparib should be offered based on identification of deleterious germline or somatic mutations in BRCA1 or BRCA2 in patients with platinum-sensitive disease.33 ASCO recommends olaparib or rucaparib maintenance therapy for a duration of 2 years and niraparib maintenance therapy for a duration of 3 years.33 A longer treatment duration may be considered in selected individuals after a discussion of risks.33 For patients who are HRD-positive, rucaparib and niraparib are options.32 Niraparib or rucaparib may be offered for non- BRCA mut/HRD-negative patients.33
ASCO strongly encourages clinicians and patients to consider the full life cycle of advanced ovarian cancer against current data (i.e., lack of overall survival benefit to date and the unknown short-term and late risks) and development of collateral resistance to other drugs (e.g., platinum agents) in determining when to use PARP inhibitors for individual care.31
In the recurrent ovarian cancer setting, ASCO states that PARP inhibitor maintenance (second-line or more) monotherapy may be offered to patients who have not already received a PARP inhibitor and who have responded to platinum-based therapy regardless of BRCA mutation status.33 Treatment may be continued until disease progression or unacceptable toxicity; options include olaparib, rucaparib, or niraparib.33 ASCO notes that maintenance treatment with niraparib for patients without germline or somatic BRCA mutation should weigh the potential progression-free survival benefit against the potential negative effect on overall survival.33
ASCO also states that PARP inhibitor monotherapy should not be routinely offered to patients for the treatment of recurrent platinum-sensitive disease and that PARP inhibitor monotherapy is not recommended for the treatment of patients with either BRCA wild-type or platinum-resistant recurrent ovarian cancer.33
Niraparib tosylate is administered orally without regard to meals at approximately the same time each day.1 The manufacturer states that bedtime administration may help relieve nausea.1
ASCO also states that a light meal or snack prior to each dose of a PARP inhibitor may mitigate nausea.31 According to ASCO, many patients will have tachyphylaxis of nausea symptoms during the first cycle of PARP inhibitor therapy, often without antiemetic therapy or dose reduction.31 If persistent nausea/vomiting, weight loss exceeding 5%, and/or reduction in performance status occurs, patients should be evaluated to rule out other causes, such as bowel obstruction.31 In the absence of other causes, ASCO recommends temporarily withholding therapy followed by dosage reduction.31
The tablets should be swallowed whole and should not be chewed, crushed, or split.1
If a dose of niraparib is missed or vomited, patients should not take an extra dose.1 The next dose should be taken at the regularly scheduled time.1
Niraparib tablets should be stored in the original bottle at 20‒25°C; excursions permitted between 15‒30°C.1
Dosage of niraparib tosylate monohydrate is expressed in terms of niraparib.1
First-line Maintenance Treatment of HRD-Positive Advanced Ovarian Cancer
The recommended adult dosage of niraparib for the first-line maintenance therapy of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with HRD-positive status defined by the presence of either a deleterious or suspected deleterious BRCA mutation and/or genomic instability is based on body weight and platelet count.1
For patients weighing less than 77 kg or with a platelet count less than 150,000/mm3, the recommended dosage is 200 mg orally once daily.1
For patients weighing 77 kg or greater and with a platelet count of 150,000/mm3 or greater, the recommended dosage is 300 mg orally once daily.1
Niraparib therapy should be initiated no later than 12 weeks following the most recent platinum-based chemotherapy regimen.1 Therapy should be continued until disease progression or unacceptable toxicity occurs.1
Maintenance Treatment of Platinum-sensitive Germline BRCA -mutated Recurrent Ovarian Cancer
The recommended adult dosage of niraparib for maintenance therapy of deleterious or suspected deleterious germline BRCA-mutated recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy is 300 mg orally once daily.1
Niraparib therapy should be initiated no later than 8 weeks following the most recent platinum-based chemotherapy regimen.1, 2 Therapy should be continued until disease progression or unacceptable toxicity occurs.1
Dosage Modification for Toxicity
Dosing interruption and/or dosage reduction or discontinuance of niraparib therapy may be necessary based on severity and persistence of an adverse effect.1 If dosage reduction from an initial dose of 300 mg once daily is necessary, the dosage should be reduced to 200 mg once daily.1 If the toxicity recurs on a dosage of 200 mg once daily, the dosage should be reduced to 100 mg once daily.1 If the toxicity recurs on a dosage of 100 mg once daily, niraparib therapy should be discontinued.1
If dosage reduction from an initial dose of 200 mg once daily is necessary, the dosage should be reduced to 100 mg once daily; if the toxicity recurs on this dose, niraparib therapy should be discontinued.1
For the first occurrence of platelet count <100,000/mm3, niraparib therapy should be withheld for no more than 28 days and CBCs should be monitored weekly until platelet counts reach or exceed 100,000/mm3.1 Niraparib therapy may then be resumed at the same dosage or at a reduced dosage.1 If platelet count is <75,000/mm3, resume at a reduced dosage.1
For a second occurrence of a platelet count <100,000/mm3, niraparib therapy should be withheld for no more than 28 days and CBCs should be monitored weekly until platelet counts reach or exceed 100,000/mm3.1 Niraparib therapy may then be resumed at a reduced dosage.1 Niraparib therapy should be discontinued if the platelet count has not returned to acceptable levels within 28 days of the dose interruption period or if the patient has already undergone dose reduction to 100 mg once daily.1
For a platelet count ≤10,000/mm3, clinicians should consider a platelet transfusion.1 If there are other risk factors (e.g., concurrent use of anticoagulation or antiplatelet drugs), clinicians should consider interrupting these drugs and/or transfusion at a higher platelet count.1 Niraparib therapy should be resumed at a reduced dose.1
For neutropenia (absolute neutrophil count [ANC] <1,000/mm3) or anemia (hemoglobin concentration <8 g/dL), niraparib therapy should be withheld for no more than 28 days and CBCs should be monitored weekly.1 Niraparib therapy may be resumed when ANC reaches or exceeds 1,500/mm3 or hemoglobin concentrations reach or exceed 9 g/dL.1 Upon resumption of therapy, the daily dosage of niraparib should be reduced.1 If ANC and/or hemoglobin concentrations do not return to acceptable levels within 28 days of withholding the drug or if the dosage has already been reduced to 100 mg once daily, niraparib therapy should be discontinued.1
If MDS/AML is confirmed, niraparib therapy should be discontinued.1
For grade 3 or greater nonhematologic toxicity that persists despite medical management, niraparib therapy should be withheld until the toxicity resolves or for no longer than 28 days.1 Upon resumption of therapy, the daily dosage of niraparib should be reduced.1
If prolonged grade 3 or greater nonhematologic toxicity (lasting more than 28 days) occurs on a dosage of 100 mg once daily, niraparib should be discontinued.1
For patients with moderate hepatic impairment (total bilirubin ≥1.5-3 times the upper limit of normal [ULN] with any AST), the manufacturer recommends an initial niraparib dosage of 200 mg once daily, regardless of body weight or platelet count.1 These patients should be monitored for hematologic toxicity, and the dosage reduced further if necessary.1 No initial dosage adjustment of niraparib is necessary in patients with mild hepatic impairment.1, 4 Niraparib has not been studied in patients with severe hepatic impairment.1
No initial dosage adjustment of niraparib is necessary in patients with mild or moderate renal impairment.1, 4 Niraparib has not been studied in patients with severe renal impairment (creatinine clearance <30 mL/minute) or end-stage renal disease requiring hemodialysis.1
The manufacturer makes no specific dosage recommendations for geriatric patients.1
Myelodysplastic Syndrome/Acute Myeloid Leukemia
Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), including fatal cases, have been reported in niraparib-treated patients.1 Overall, MDS/AML have been reported in 18 of 381 patients receiving niraparib versus 5 of 190 patients treated with placebo in clinical studies (PRIMA and NOVA).1 All of these patients had received previous chemotherapy with platinum-containing agents and/or other DNA-damaging antineoplastic agents and radiotherapy.1 The duration of niraparib therapy in patients who developed MDS/AML varied from 3.6 months to 5.9 years.1
Complete blood cell (CBC) counts should be monitored in patients receiving niraparib.1 If MDS/AML is confirmed, niraparib should be discontinued.1
Adverse hematologic effects (e.g., thrombocytopenia, anemia, neutropenia) have been reported in patients receiving niraparib therapy.1 In the PRIMA study, grade 3 or greater thrombocytopenia, anemia, and neutropenia occurred in 39, 31, and 21%, respectively, of patients receiving niraparib.1 Discontinuance of therapy was necessary in 4, 2, and 2% of patients experiencing thrombocytopenia, anemia, and neutropenia, respectively.1 In patients who received a weight- or platelet count-based initial dose of niraparib, grade 3 or greater thrombocytopenia, anemia, and neutropenia occurred in 22, 23, and 15%, respectively.1 Discontinuance of therapy was necessary in 3, 3, and 2% of patients experiencing thrombocytopenia, anemia, and neutropenia, respectively.1 In the NOVA study, grade 3 or greater thrombocytopenia, anemia, and neutropenia occurred in 29, 25, and 20%, respectively, of patients receiving niraparib.1 Discontinuance of therapy was necessary in 3, 1, and 2% of patients experiencing thrombocytopenia, anemia, and neutropenia, respectively.1
Niraparib therapy should not be initiated until patients have recovered from hematologic toxicity caused by previous chemotherapy (to grade 1 or less).1 CBC counts should be monitored weekly for the first month of therapy, monthly for the next 11 months, and then periodically thereafter.1 If hematologic toxicity develops and persists for more than 28 days following interruption of niraparib therapy, patients should be referred to a hematologist for further evaluation, including bone marrow analysis and cytogenetic testing of a blood sample.1
Hypertension and hypertensive crisis have been reported in niraparib-treated patients.1
In the PRIMA study, grade 3 or greater hypertension occurred in 6% of niraparib-treated patients compared with 1% of those receiving placebo; discontinuance of therapy was not necessary in any patient.1 Median time to onset was 43 days (range: 1-531 days), and median duration of hypertension was 12 days (range: 1-61 days).1 Maximum mean increases from baseline in pulse rate, systolic blood pressure, and diastolic blood pressure were 22.4 beats per minute, 24.4 mm Hg, and 15.9 mm Hg, respectively, in patients receiving niraparib compared with 14 beats per minute, 19.6 mm Hg, and 13.9 mm Hg, respectively, in those receiving placebo.1
In the NOVA study, grade 3 or greater hypertension occurred in 9% of niraparib-treated patients compared with 2% of those receiving placebo; discontinuance of therapy was necessary in less than 1% of patients receiving niraparib or placebo.1 Median time to onset was 77 days (range: 4-504 days), and median duration of hypertension was 15 days (range: 1-86 days).1 Maximum mean increases from baseline in pulse rate, systolic blood pressure, and diastolic blood pressure were 24.1 beats per minute, 24.5 mm Hg, and 16.5 mm Hg, respectively, in patients receiving niraparib compared with 15.8 beats per minute, 18.3 mm Hg, and 11.6 mm Hg, respectively, in those receiving placebo.1
In a randomized, placebo-controlled study in patients with cancer, substantial changes in the mean QT interval corrected for rate (QTc) (i.e., greater than 20 msec) were not observed when niraparib 300 mg was administered once daily.1
Blood pressure and heart rate should be monitored at least weekly for the first 2 months of niraparib therapy, then monthly for the first year and periodically thereafter.1 Patients with cardiovascular disorders, particularly those with coronary insufficiency, cardiac arrhythmias, and/or hypertension, should be closely monitored.1 Hypertension should be managed with antihypertensive therapy and adjustment of the niraparib dosage, if necessary.1
Posterior Reversible Encephalopathy Syndrome
In clinical trials, posterior reversible encephalopathy syndrome occurred in 0.1% of 2165 patients; it has also been described in postmarketing reports.1
Patients should be monitored for signs and symptoms of posterior reversible encephalopathy syndrome, including seizure, headache, altered mental status, visual disturbance, and cortical blindness with or without associated hypertension.1 The diagnosis of posterior reversible encephalopathy syndrome requires confirmation by brain imaging (preferably magnetic resonance imaging).1 If posterior reversible encephalopathy syndrome is suspected, niraparib should be discontinued promptly, and appropriate treatment should be initiated.1 The safety of restarting niraparib in patients who previously experienced posterior reversible encephalopathy syndrome is not known.1
Fetal/Neonatal Morbidity and Mortality
Based on its mechanism of action, niraparib may cause fetal harm (e.g., teratogenicity, embryofetal death) in humans.1 There are no data regarding use of niraparib in pregnant women to inform the drug-associated risk.1 Niraparib has the potential to cause teratogenicity and/or embryofetal death since the drug is genotoxic and targets actively dividing cells in animals and patients (e.g., bone marrow).1 Due to the potential risk to the fetus based on its mechanism of action, animal developmental and reproductive toxicology studies have not been conducted with niraparib.1
Pregnancy should be avoided during niraparib therapy.1 Pregnancy status should be verified prior to starting niraparib therapy.1 Females of reproductive potential should be advised to use effective contraceptive methods while receiving niraparib and for at least 6 months after discontinuance of therapy.1 If niraparib is used during pregnancy or if the patient becomes pregnant while receiving the drug, the patient should be apprised of the potential risk to the fetus and the potential risk for loss of the pregnancy.1
Although there are no available data in pregnant women, niraparib may cause fetal harm based on its mechanism of action.1 If niraparib is used during pregnancy or if the patient becomes pregnant while receiving the drug, the patient should be apprised of the potential fetal hazard and potential for loss of the pregnancy.1
In females of reproductive potential, the manufacturer recommends a pregnancy test prior to initiating niraparib therapy.1
It is not known whether niraparib or its metabolites are distributed into human milk or if the drug has any effect on milk production or the breast-fed infant.1 Because of the potential for serious adverse reactions to niraparib in breast-fed infants, women should be advised to discontinue breast-feeding while receiving the drug and for 1 month after last dose.1
Females and Males of Reproductive Potential
Females of reproductive potential should be advised to use effective contraceptive methods while receiving niraparib and for at least 6 months after discontinuance of therapy.1 If niraparib is used during pregnancy or if the patient becomes pregnant while receiving the drug, the patient should be apprised of the potential risk to the fetus and the potential risk for loss of the pregnancy.1
Results of animal studies suggest that niraparib may impair male fertility.1 The effect of the drug on fertility in humans is not known.1
Fertility studies have not been conducted with niraparib in animals.1 In a general toxicity study, reduced sperm, spermatids, and germ cells in epididymides and testes were observed in male animals receiving niraparib at exposure levels approximately 0.3 and 0.012 times the human exposure at a dose of 300 mg daily.1 A trend toward reversibility of these findings 4 weeks after discontinuance of therapy was observed.1
Safety and efficacy of niraparib have not been established in pediatric patients.1
In the PRIMA study, 39% of patients were 65 years of age or older and 10% were 75 years of age or older.1 In the NOVA study, 35% of patients were 65 years of age or older and 8% were 75 years of age or older.1 No overall differences in safety and efficacy were observed between geriatric patients and younger adults.1 However, the possibility of increased sensitivity to the drug in some geriatric patients cannot be ruled out.1
In pharmacokinetic studies, mild hepatic impairment had no clinically significant effect on the pharmacokinetics of niraparib; therefore, no initial dosage adjustment of niraparib is necessary in such patients.1
In patients with moderate hepatic impairment (total bilirubin ≥1.5-3 times the ULN with any AST), the niraparib area under the serum concentration-time curve (AUC) was 1.6 times higher than the AUC observed in patients with normal hepatic function.1 Therefore, a reduction in the initial dosage of niraparib is recommended for such patients.1
Pharmacokinetics and safety of niraparib in patients with severe hepatic impairment have not been evaluated to date.1, 4
Population pharmacokinetic analyses indicate that the pharmacokinetics of niraparib in patients with mild or moderate renal impairment (creatinine clearance 30-90 mL/minute) are similar to those in patients with normal renal function; therefore, no initial dosage adjustment of the drug is necessary in such patients.1, 4
Pharmacokinetics and safety of niraparib in patients with severe renal impairment (creatinine clearance <30 mL/minute) or end-stage renal disease requiring hemodialysis have not been established to date.1
Adverse effects reported in 10% or more of patients receiving niraparib include nausea, thrombocytopenia, anemia, fatigue, constipation, musculoskeletal pain, abdominal pain, vomiting, neutropenia, decreased appetite, leukopenia, insomnia, headache, dyspnea, rash, diarrhea, hypertension, cough, dizziness, acute kidney injury, urinary tract infection, and hypomagnesemia.1
Niraparib is principally metabolized by carboxylesterases to form a major inactive metabolite, M1, which subsequently undergoes glucuronidation.1, 4 In vitro studies indicate that niraparib is not an inhibitor of UGT1A1, UGT1A4, UGT1A9, or UGT2B7.1
In vitro studies indicate that neither niraparib nor its major metabolite (M1) are inhibitors of cytochrome P-450 (CYP) isoenzymes 1A, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A or inducers of CYP3A.1, 4
Niraparib is an inhibitor of multidrug and toxin extrusion (MATE) 1 and 2K, but is not a substrate of MATE1 or 2K.1 The M1 metabolite is a substrate but not an inhibitor of MATE1 and 2K.1 In vitro studies indicate that niraparib is a substrate, but not an inhibitor, of P-glycoprotein (P-gp).1 Niraparib is also a substrate and inhibitor of breast cancer resistance protein (BCRP).1 In vitro, neither niraparib nor M1 is a substrate or inhibitor of bile salt export pump (BSEP),1, 8 organic anion transport protein (OATP) 1B1, OATP1B3, organic cation transporter (OCT) 1, OCT2, organic anion transporter (OAT) 1, and OAT3.1, 4 In vitro studies also show that M1 is not a substrate or inhibitor of P-gp and BCRP.1 Neither niraparib nor M1 is a substrate or inhibitor of multidrug resistance-associated protein (MRP) 2.1
Drugs Affecting Gastric Acidity
Although not specifically studied in drug interaction studies to date, clinically important pharmacokinetic interactions between niraparib and drugs affecting gastric acidity (e.g., histamine H2-receptor antagonists, proton-pump inhibitors) appear unlikely based on the drug's solubility in an acidic pH range.4
Anticoagulants and Antiplatelet Agents
There is a potential for increased risk of adverse hematologic effects and hemorrhagic events in patients concurrently receiving niraparib and anticoagulants or antiplatelet agents.1
Niraparib, an inhibitor of mammalian poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) enzymes PARP-1 and PARP-2, is an antineoplastic agent.1 The drug is a highly selective inhibitor of PARP-1 and PARP-2, which are involved in detection of DNA damage and its repair.1, 2 In vitro studies have demonstrated that niraparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes, which result in DNA damage, apoptosis, and cell death.1 In vitro, niraparib exhibits cytotoxic activity in tumor cell lines with or without deficiencies in BRCA1/2 .1 In addition, niraparib reduced tumor growth in xenograft models of human cancer cell lines with BRCA1/2 deficiencies in mice and in patient-derived xenograft tumor models with HRD expressing either mutated or wild-type BRCA1/2 .1, 7
Following oral administration, the absolute bioavailability of niraparib is approximately 73%.1, 4 Peak plasma concentrations and AUCs of niraparib are proportional to dose following repeated administration of the drug over the dosage range of 30-400 mg once daily.1, 6 Following oral administration, niraparib is rapidly absorbed with peak plasma concentrations occurring within 5 hours.1, 4, 6 Oral administration of niraparib with a high-fat meal (800-1000 calories with fat accounting for approximately 50% of the caloric content) resulted in an increase in peak plasma concentrations of 11% and an increase in AUC of 28%; however, these effects were not considered clinically important.1, 4 The drug is 83% bound to plasma proteins.1 The mean half-life of niraparib is 50 hours.1, 6 Niraparib is metabolized to inactive metabolites by carboxylesterases followed by glucuronidation.1, 4 Following oral administration of a single radiolabeled dose of niraparib, 48% of the dose was recovered in urine (11% of the dose as unchanged drug) and 39% was recovered in feces (19% of the dose as unchanged drug).1 Population pharmacokinetic analyses indicate that age (18-65 years), race/ethnicity, and mild to moderate renal impairment do not have clinically important effects on the pharmacokinetics of niraparib.1, 4
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets | 100 mg (of niraparib) | GlaxoSmithKline | |
200 mg (of niraparib) | Zejula® | GlaxoSmithKline | ||
300 mg (of niraparib) | Zejula® | GlaxoSmithKline |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions July 10, 2026. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. GlaxoSmithKline. Zejula® (niraparib tosylate) tablets prescribing information. Durham, NC; 2026 Mar.
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