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Niraparib is an

Oral active poly (ADP-ribose) polymerase (PARP) inhibitor.

By blocking the enzymes responsible for

DNA repair, niraparib induces cytotoxicity in cancer cells.

Niraparib is selective towards

First approved by the FDA on

March 27, 2017, 3 niraparib is used to treat epithelial ovarian, fallopian tube, or primary peritoneal cancer.

Niraparib was approved by the European Commission on November 16, 2017 7 and by Health Canada on June 27, 2019.

On December 12, 2025, the FDA expanded niraparib and abiraterone acetate (AKEEGA) with prednisone for the treatment of patients with BRCA2-mutated metastatic castration-sensitive prostate cancer (mCSPC). 12, 11.

Niraparib is indicated for the maintenance treatment of adult patients with advanced or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. 6, 7, 8 In Canada and the US, niraparib is also available in a with abiraterone, which is indicated with prednisone for the treatment of adults with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC). 9, 10 In Canada, this is also used with prednisolone and is reserved for patients who are asymptomatic or mildly symptomatic, and in whom chemotherapy is not clinically indicated.

In the

US, niraparib and abiraterone acetate with prednisone is also indicated for adults with deleterious or suspected deleterious BRCA2-mutated metastatic castration-sensitive prostate cancer (mCSPC). 12,

Niraparib mediated cytotoxic effects in tumour cell lines with or without deficiencies in BRCA1/2.

Decreased tumour growth was observed in both mouse xenograft models of human cancer cell lines with deficiencies in BRCA1/2 and human patient-derived xenograft tumour models with homologous recombination deficiency (HRD) that had either mutated or wild-type BRCA1/2.

In vitro studies suggest that niraparib inhibits dopamine, norepinephrine, and serotonin transporters, which may explain its off-target cardiovascular effects such as increased pulse rate and blood pressure.

Poly polymerase 1 Inhibitor Poly polymerase 2 Inhibitor.

Following a single-dose administration of 300 mg niraparib, the mean (±SD) peak plasma concentration (C max ) was 804 (±403) ng/mL.

The exposure (C max and AUC) of niraparib increased in a dose-proportional manner with daily doses ranging from 30 mg (0.1 times the approved recommended dose) to 400 mg (1.3 times the approved recommended dose).

The accumulation ratio of niraparib exposure following 21 days of repeated daily doses was approximately 2-fold for doses ranging from 30-400 mg. The Tmax is about three hours.

The absolute bioavailability of niraparib is approximately 73%.

Food does not appear to affect drug exposure.

The average (±SD) apparent volume of distribution (Vd/F) was 1,220 (±1,114) L. In a population pharmacokinetic analysis, the Vd/F of niraparib was 1,074 L in patients with cancer.

Niraparib is primarily metabolized by carboxylesterases (CEs) to form M1, which is a major inactive metabolite.

M1 metabolite can subsequently undergo glucuronidation mediated by UDP-glucuronosyltransferases (UGTs) to form the M10 metabolite.

In a mass balance study, M1 and M10 were the major circulating metabolites.

M1 metabolite can also undergo methylation, monooxygenation, and hydrogenation to form other minor metabolites.

Hover over products below to view reaction partners Niraparib Niraparib M1 metabolite Niraparib M10 metabolite.

Niraparib is eliminated via multiple pathways, including liver metabolism, hepatobiliary excretion, and renal elimination.

Following administration of a single oral 300-mg dose of radio-labeled niraparib, the average percent recovery of the administered dose over 21 days was 47.5% (range: 33.4% to 60.2%) in urine and 38.8% (range: 28.3% to 47.0%) in feces.

In pooled samples collected over 6 days, unchanged niraparib accounted for 11% and 19% of the administered dose recovered in urine and feces, respectively.

Following multiple daily doses of 300 mg of niraparib, the mean half-life (t 1/2 ) is 36 hours.

In a population pharmacokinetic analysis, the apparent total clearance (CL/F) of niraparib was 16.2 L/h in patients with cancer.

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There is limited information available regarding the acute toxicity profile and overdosage of niraparib.

BRCA2 m mCSPC: The recommended dosage of AKEEGA is 200 mg niraparib/1,000 mg abiraterone acetate orally once daily in combination with 5 mg prednisone daily until disease progression or unacceptable toxicity.

BRCA m mCRPC

The recommended dosage of AKEEGA is 200 mg niraparib/1,000 mg abiraterone acetate orally once daily in combination with 10 mg prednisone daily until disease progression or unacceptable toxicity.

Patients receiving

AKEEGA should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy.

AKEEGA on an empty stomach at least one hour before or two hours after food.

For adverse reactions, consider interruption of treatment, dose reduction, or dose discontinuation. 2.1 Patient Selection Select patients for the treatment of mCSPC with AKEEGA based on the presence of a BRCA2 gene alteration.

Select patients for the treatment of mCRPC with AKEEGA based on the presence of a BRCA gene alteration.

Information on

FDA-approved tests is available at: 2.2 Recommended Dosage BRCA2.

• mutated ( BRCA2 m) Metastatic Castration-Sensitive Prostate Cancer (mCSPC) The recommended dosage of AKEEGA is 200 mg niraparib/1,000 mg abiraterone acetate orally once daily in combination with 5 mg prednisone once daily until disease progression or unacceptable toxicity.

BRCA -mutated ( BRCA m) Metastatic Castration-Resistant Prostate Cancer (mCRPC) The recommended dosage of AKEEGA is 200 mg niraparib/1,000 mg abiraterone acetate orally once daily in combination with 10 mg prednisone once daily until disease progression or unacceptable toxicity.

Swallow tablets whole with water.

Do not break, crush, or chew tablets.

If a patient misses a dose, instruct patients to take the dose as soon as possible on the same day and resume their next dose at the normal schedule the following day. 2.3 Dosage Modification for Adverse Reactions The recommended dosage modifications for AKEEGA are provided in Table 1.

Treatment with

AKEEGA should not be reinitiated until the toxicity has resolved to Grade 1 or baseline.

If the toxicity is attributed to one component of AKEEGA, the other component of AKEEGA may be continued as a single agent at the current dose until the adverse reaction resolves and AKEEGA can be resumed.

Table 1: Dosage Modifications for Adverse Reactions Adverse Reaction Severity Dosage Modification Myelosuppression Hemoglobin <8 g/dL Withhold AKEEGA and monitor blood counts weekly.

When hemoglobin returns to ≥9 g/dL, resume at the reduced dose of AKEEGA 100 mg/1,000 mg once daily and monitor blood counts weekly for 28 days and as clinically indicated.

Permanently discontinue

AKEEGA if hemoglobin 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/1,000 mg once daily.

If myelodysplastic syndrome or acute myeloid leukemia (MDS/AML) is confirmed, discontinue AKEEGA.

Platelet count <100,000/mcL First occurrence: Withhold AKEEGA for a maximum of 28 days and monitor blood counts weekly until platelet counts return to ≥100,000/mcL.

AKEEGA at same or the reduced dose of 100 mg/1,000 mg once daily.

If platelet count is <75,000/mcL, resume at the reduced dose of AKEEGA 100 mg/1,000 mg once daily.

Second occurrence

Withhold AKEEGA for a maximum of 28 days and monitor blood counts weekly until platelet counts return to ≥100,000/mcL.

Resume at the reduced dose of

AKEEGA 100 mg/1,000 mg once daily.

AKEEGA 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/1,000 mg once daily.

Neutrophil <1,000/mcL Withhold AKEEGA and monitor blood counts weekly.

When neutrophil counts return to ≥1,500/mcL, resume at the reduced dose of AKEEGA 100 mg/1,000 mg once daily and monitor blood counts weekly for 28 days and as clinically indicated.

AKEEGA if neutrophils have 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/1,000 mg once daily.

Hematologic adverse reaction requiring transfusion

Consider platelet transfusion for patients with platelet count ≤10,000/mcL.

If there are other risk factors such as coadministration of anticoagulation or antiplatelet drugs, consider interrupting these drugs and/or transfusion at a higher platelet count.

ALT and/or AST greater than 5 × ULN or total bilirubin greater than 3 × ULN Withhold AKEEGA and closely monitor liver function.

Permanently discontinue AKEEGA if

ALT or AST ≥ 20 times the ULN – OR– ALT > 3 × ULN and total bilirubin > 2 × ULN in the absence of biliary obstruction or other causes responsible for the concurrent elevation -OR.

• Hepatotoxicity recurs at the reduced dose 100 mg/500 mg. When AST and ALT resolves to less ≤ 2.5 × ULN and total bilirubin ≤ 1.5 × ULN, AKEEGA may be resumed at the reduced dose of 100 mg/500 mg once daily.

When resumed, monitor serum transaminases every two weeks for three months, monthly thereafter, and as clinically indicated.

Other non-hematological adverse reactions that persist despite medical management Grade 3 or 4 Discontinue AKEEGA in patients who develop hypertensive crisis or other severe cardiovascular adverse reactions.

AKEEGA until resolution of adverse reaction or for a maximum of 28 days.

If resolves in 28 days or less, AKEEGA may be resumed at the reduced dose.

AKEEGA if adverse reaction(s) has not resolved after 28 days or Grade 3 or 4 adverse reaction reoccurs after dose reduction.

® (niraparib and abiraterone acetate) tablets are available in the strengths and packages listed below: AKEEGA 50 mg/500 mg film-coated tablets Yellowish orange to yellowish brown, oval, film-coated tablets debossed with "N 50 A" on one side and plain on the other side.

They are available in bottles of 60 tablets.

NDC 57894-050-60 AKEEGA 100 mg/500 mg film-coated tablets Orange, oval, film-coated tablets debossed with "N 100 A" on one side and plain on the other side.

NDC 57894-100-60 Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) .

Based on its mechanism of action, AKEEGA may harm a developing fetus.

Females who are or may become pregnant should handle AKEEGA tablets with protection, e.g., gloves.

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

Based on its mechanism of action, AKEEGA may harm a developing fetus.

Females who are or may become pregnant should handle AKEEGA tablets with protection, e.g., gloves.

Risk Summary The safety and efficacy of AKEEGA have not been established in females.

Based on findings from animal studies and mechanism of action, AKEEGA can cause fetal harm and potential loss of pregnancy.

There are no human data on the use of AKEEGA in pregnant women.

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 (e.g., bone marrow) .

Due to the potential risk to a fetus based on its mechanism of action, animal developmental and reproductive toxicology studies were not conducted with niraparib.

In animal reproduction studies, oral administration of abiraterone acetate to pregnant rats during organogenesis caused adverse developmental effects at maternal exposures approximately ≥ 0.03 times the human exposure (AUC) at the recommended dose.

Niraparib is genotoxic and targets actively dividing cells.

Animal developmental and reproductive toxicology studies were not conducted with niraparib.

In an embryo-fetal developmental toxicity study in rats, abiraterone acetate caused developmental toxicity when administered at oral doses of 10, 30 or 100 mg/kg/day throughout the period of organogenesis (gestational days 6–17).

Findings included embryo-fetal lethality (increased post implantation loss and resorptions and decreased number of live fetuses), fetal developmental delay (skeletal effects) and urogenital effects (bilateral ureter dilation) at doses ≥10 mg/kg/day, decreased fetal ano-genital distance at ≥30 mg/kg/day, and decreased fetal body weight at 100 mg/kg/day. Doses ≥10 mg/kg/day caused maternal toxicity.

The doses tested in rats resulted in systemic exposures (AUC) approximately 0.03, 0.1 and 0.3 times, respectively, the AUC in patients receiving 1,000 mg daily of abiraterone acetate.

Safety and effectiveness of

AKEEGA in pediatric patients have not been established.

Of the 162 patients with BRCA2 gene alteration(s) who received AKEEGA in AMPLITUDE, 40% of patients were less than 65 years, 36% of patients were 65 years to 74 years, and 23% were 75 years and over.

Of the 113 patients with BRCA gene alteration(s) who received AKEEGA in MAGNITUDE, 34.5% of patients were less than 65 years, 38.9% of patients were 65 years to 74 years, and 26.5% were 75 years and over.

No overall differences in effectiveness were observed between patients 65 years of age or older and younger patients in AMPLITUDE or MAGNITUDE.

Patients 75 years of age or older who received AKEEGA experienced a higher incidence of fatal adverse reactions than younger patients.

The incidence of fatal adverse reactions was 4.3% in patients younger than and 13% in patients 75 or older.