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AKEEGA®

(niraparib and abiraterone acetate)

This information is intended for US healthcare professionals to access current scientific information about J&J Innovative Medicine products. It is prepared by Medical Information and is not intended for promotional purposes, nor to provide medical advice.

AKEEGA® (niraparib and abiraterone acetate)

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AKEEGA® - Dosage and Administration

Last Updated: 10/23/2024

Indication1

  • AKEEGA with prednisone is indicated for the treatment of adult patients with deleterious or suspected deleterious BRCAm mCRPC. Select patients for therapy based on an FDA-approved test for AKEEGA.
  • Please refer to the full PRESCRIBING INFORMATION for complete information.

Dosage and Administration1

  • The recommended dosage of AKEEGA is 200 mg niraparib/1000 mg abiraterone acetate orally once daily in combination with 10 mg prednisone daily until disease progression or unacceptable toxicity.
    • Take AKEEGA on an empty stomach. Do not eat food 2 hours before and 1 hour after taking AKEEGA.
  • For ARs, consider interruption of treatment, dose reduction, or dose discontinuation.

Use in Specific Populations1

  • Safety and effectiveness of AKEEGA in pediatric patients have not been established.
  • There was an insufficient number of patients with BRCA gene alteration(s) treated with AKEEGA in the MAGNITUDE study to accurately characterize the efficacy or safety by age.
  • Avoid use of AKEEGA in patients with moderate or severe hepatic impairment.
    • No dosage modification is necessary for patients with mild hepatic impairment.
  • Monitor patients with severe renal impairment for increased ARs and modify dosage as recommended for ARs.
    • No dosage modification is recommended for patients with mild to moderate renal impairment.

Note: AR, adverse reaction; BRCAm, BRCA-mutated; mCRPC, metastatic castration-resistant prostate cancer.

Indication

  • AKEEGA with prednisone is indicated for the treatment of adult patients with deleterious or suspected deleterious BRCAm mCRPC.1
  • Select patients for therapy based on an FDA-approved test for AKEEGA.1

Patient Selection

  • Select patients for the treatment of mCRPC with AKEEGA based on the presence of a BRCA gene alteration.1
  • Information on FDA-approved tests is available at: http://www.fda.gov/CompanionDiagnostics.
  • Data from the BEDIVERE study supported comparable pharmacokinetics for niraparib 200 mg compared with niraparib 300 mg. Both were taken in combination with abiraterone acetate and prednisone.2
  • No (0%) patients experienced DLTs in the group receiving niraparib 200 mg in combination with abiraterone acetate and prednisone. Three (37.5%) patients experienced DLTs in the group receiving niraparib 300 mg in combination with abiraterone acetate and prednisone.2
  • Based on a more tolerable safety profile and comparable pharmacokinetics, niraparib 200 mg in combination with abiraterone acetate and prednisone was selected as the recommended phase 2 dose.2
  • The AKEEGA DAT was developed with the aim of simplifying the combination regimen by reducing the pill burden for cancer patients receiving multiple oral medications.3
  • The reduced-strength (50 mg niraparib/500 mg abiraterone acetate) tablet was developed to address the need for patients who may require a lower dosage of niraparib due to reports of toxicity (eg, anemia, thrombocytopenia, and neutropenia).3
  • A tablet formulation with reduced strength of abiraterone acetate is not being developed given the low rate of abiraterone acetate dose reduction in the groups receiving niraparib in combination with abiraterone acetate and prednisone in the BEDIVERE study.3
  • No additional published data regarding the dose rationale for AKEEGA has been identified. For further details, please refer to the clinical trial protocol for the MAGNITUDE study.3
  • Treatment with AKEEGA should not be reinitiated until the toxicity has resolved to grade 1 or baseline.1
  • If the toxicity is attributed to 1 component of AKEEGA, the other component of AKEEGA may be continued as a single agent at the current dose until the AR resolves and AKEEGA can be resumed.1
Hemoglobin
<8 g/dL
Withholding / Monitoring
  • Withhold AKEEGA and monitor blood counts weekly.1
Dosage Modification
  • When hemoglobin levels return to ≥9 g/dL, resume AKEEGA at the reduced dose of 100 mg/1000 mg once daily and monitor blood counts weekly for 28 days and as clinically indicated.1,a
Discontinuation
  • Permanently discontinue AKEEGA if hemoglobin levels 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/1000 mg once daily (discontinue AKEEGA if MDS/AML is confirmed).1
Platelet
<100,000/mcL
First Occurrence
Withholding / Monitoring
  • Withhold AKEEGA for a maximum of 28 days and monitor blood counts weekly until platelet counts return to ≥100,000/mcL.1,a
Dosage Modification
  • Resume AKEEGA at the same or the reduced dose of 100 mg/1000 mg once daily.1
  • If platelet count is <75,000/mcL, resume AKEEGA at the reduced dose 100 mg/1000 mg once daily.1,a
Second Occurrence
Withholding / Monitoring
  • Withhold AKEEGA for a maximum of 28 days and monitor blood counts weekly until platelet counts return to ≥100,000/mcL.1,a
Dosage Modification
  • Resume AKEEGA at the reduced dose of 100 mg/1000 mg once daily.1
Discontinuation
  • Permanently discontinue 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/1000 mg once daily (discontinue AKEEGA if MDS/AML is confirmed).1

aTreatment with AKEEGA should not be reinitiated until the toxicity has resolved to grade 1 or baseline.

ALT and/or AST >5xULN
or Total Bilirubin >3xULN
Withholding / Monitoring
  • Withhold AKEEGA and closely monitor liver function.1
Dosage Modification
  • When AST and ALT resolve to ≤2.5xULN and total bilirubin to ≤1.5xULN, AKEEGA may be resumed at the reduced dose of 100 mg/500 mg once daily. When resumed, monitor serum transaminases every 2 weeks for 3 months, monthly thereafter, and as clinically indicated.1,a
Discontinuation
  • Permanently discontinue AKEEGA if1:
    • ALT or AST ≥20xULN, or
    • ALT >3xULN and total bilirubin >2xULN in the absence of biliary obstruction or other causes responsible for the concurrent elevation, or
    • Hepatotoxicity recurs at the reduced dose of 100 mg/500 mg.

aTreatment with AKEEGA should not be reinitiated until the toxicity has resolved to grade 1 or baseline.

Grade 3 or 4
Withholding / Monitoring
  • Withhold AKEEGA until resolution of AR or for a maximum of 28 days.1
Dosage Modification
  • If resolved in 28 days or less, AKEEGA may be resumed at the reduced dose.1
Discontinuation
  • Permanently discontinue AKEEGA if AR(s) has not resolved after 28 days, or grade 3 or 4 AR reoccurs after dose reduction.1
  • Discontinue AKEEGA in patients who develop hypertensive crisis or other severe cardiovascular ARs.1

Pediatric Use

  • Safety and effectiveness of AKEEGA in pediatric patients have not been established.1

Geriatric Use

  • Of the 113 patients with BRCA gene alteration(s) who received AKEEGA in the MAGNITUDE study, 34.5% of patients were <65 years old, 38.9% of patients were 65-74 years old, and 26.5% were ≥75 years old.1
  • There was an insufficient number of patients with BRCA gene alteration(s) treated with AKEEGA in the MAGNITUDE study to accurately characterize the efficacy or safety by age.1

Hepatic Impairment

  • Avoid use of AKEEGA in patients with moderate or severe hepatic impairment.1
  • No dosage modification is necessary for patients with mild hepatic impairment.1

Renal Impairment

  • Monitor patients with severe renal impairment for increased ARs and modify dosage as recommended for ARs.1
  • No dosage modification is recommended for patients with mild to moderate renal impairment.1
ALT Alanine transaminase DLT Dose-limiting toxicity
AML Acute myeloid leukemia FDA Food and Drug Administration
AR Adverse reaction GnRH Gonadotropin-releasing hormone
AST Aspartate transaminase mCRPC Metastatic castration-resistant prostate cancer
BRCAm BRCA-mutated MDS Myelodysplastic syndrome
DAT Dual action tablet ULN Upper limit of normal

A literature search of MEDLINE®, Embase®, BIOSIS Previews®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 24 September 2024.

  1. AKEEGA (niraparib and abiraterone acetate) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/AKEEGA-pi.pdf.
  2. Saad F, Chi KN, Shore ND, et al. Niraparib with androgen receptor-axis-targeted therapy in patients with metastatic castration-resistant prostate cancer: safety and pharmacokinetic results from a phase 1b study (BEDIVERE). Cancer Chemother Pharmacol. 2021;88(1):25-37.
  3. Chi KN, Rathkopf D, Smith MR, et al. Protocol for: Niraparib and abiraterone acetate for metastatic castration-resistant prostate cancer. J Clin Oncol. 2023;41(18):3339-3351.