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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 Modifications

Last Updated: 05/31/2024

SUMMARY

Please refer to the full PRESCRIBING INFORMATION for complete information.¹
AKEEGA tablets are available in the strengths listed below¹^,²:
- 50 mg niraparib/500 mg abiraterone acetate film-coated tablets
- 100 mg niraparib/500 mg abiraterone acetate film-coated tablets
The recommended dosage of AKEEGA is 200 mg niraparib/1000 mg abiraterone acetate (two 100 mg/500 mg tablets) orally once daily in combination with 10 mg prednisone daily until disease progression or unacceptable toxicity.¹
For adverse reactions, consider interruption of treatment, dose reduction, or dose discontinuation. The recommended dosage modifications for AKEEGA are described in Table: Dosage Modification for Adverse Reactions.¹

DOsAGE modifications

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 adverse reaction resolves and AKEEGA can be resumed.¹

Dosage Modification for Adverse Reactions¹

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/1000 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/1000 mg once daily.^a
	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. Resume AKEEGA at the same or the reduced dose of 100 mg/1000 mg once daily. If platelet count is <75,000/mcL, resume at the reduced dose of AKEEGA 100 mg/1000 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/1000 mg once daily. 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.^a
	Neutrophil <1000/mcL	Withhold AKEEGA and monitor blood counts weekly. When neutrophil counts return to ≥1500/mcL, resume at the reduced dose of AKEEGA 100 mg/1000 mg once daily and monitor blood counts weekly for 28 days and as clinically indicated. Permanently discontinue 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/1000 mg once daily.^a
	Hematologic adverse reaction requiring transfusion	Consider platelet transfusion for patients with a platelet count of ≤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. Resume at the reduced dose of AKEEGA 100 mg/1000 mg once daily.
Hepatotoxicity	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×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 resolve to ≤2.5×ULN and total bilirubin to ≤1.5×ULN, 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.
Other nonhematological adverse reactions that persist despite medical management	Grade 3 or 4ᵇ	Withhold 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. Permanently discontinue AKEEGA if adverse reaction(s) has not resolved after 28 days, or grade 3 or 4 adverse reaction reoccurs after dose reduction.
Abbreviations: ALT, alanine transaminase; AML, acute myeloid leukemia; AST, aspartate transaminase; MDS, myelodysplastic syndrome; ULN, upper limit of normal. ^aIf MDS/AML is confirmed, discontinue AKEEGA. ^bDiscontinue AKEEGA in patients who develop hypertensive crisis or other severe cardiovascular adverse reactions.

Dosage Modification in Specific Populations

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 adverse reactions and modify dosage as recommended for adverse reactions.¹
No dosage modification is recommended for patients with mild to moderate renal impairment.¹

DOSE RATIONALE

Data from the BEDIVERE study supported comparable pharmacokinetics (PK) for niraparib 200 mg compared to niraparib 300 mg. Both were taken in combination with abiraterone acetate with prednisone (AAP).³
No (0%) patients experienced dose-limiting toxicities (DLTs) in the niraparib 200 mg in combination with AAP group. Three (37.5%) patients experienced DLTs in the niraparib 300 mg in combination with AAP group.³
Based on a more tolerable safety profile and comparable PK, niraparib 200 mg in combination with AAP was selected as the recommended phase 2 dose (RP2D).³
The AKEEGA dual action tablet (DAT) was developed with the aim of simplifying the combination regimen by reducing the pill burden for cancer patients receiving multiple oral medications.⁴
The low-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).⁴
- A tablet formulation with a lower strength of abiraterone acetate is not being developed given the low rate of abiraterone acetate dose reduction in the niraparib in combination with AAP groups in the BEDIVERE study.⁴
No additional published data regarding the rationale for the AKEEGA DAT was identified. For further details, please refer to the clinical trial protocol for the MAGNITUDE study.⁴

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 20 May 2024.

References

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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	Chi KN, Rathkopf D, Smith MR, et al. Niraparib and abiraterone acetate for metastatic castration-resistant prostate cancer. J Clin Oncol. 2023;41(18):3339-3351.
3	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.
4	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.