Akeega (niraparib and abiraterone acetate) plus prednisone for BRCA2-mutated metastatic castration-sensitive prostate cancer

Initial US Approval:

2023

Key Clinical Studies:

AMPLITUDE (NCT04497844)

Drug Class/Description:

a combinationof niraparib, a poly(ADP-ribose) polymerase (PARP)inhibitor, and abiraterone acetate, a CYP17 inhibitor

Indications and Usage:

AKEEGA is a combination of niraparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, and abiraterone acetate, a CYP17 inhibitor indicated with prednisone for the treatment of adult patients with:

• deleterious or suspected deleterious BRCA2-mutated (BRCA2m) metastatic castration-sensitive prostate cancer (mCSPC). 
• deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC).
• Select patients for therapy based on an FDA-approved test for AKEEGA.

Dosage and Administration:

BRCA2m 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. 

BRCAm 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.
• Take AKEEGA on an empty stomach at least one hour before ort wo hours after food.
• For adverse reactions, consider interruption of treatment, dose reduction, or dose discontinuation.

Dosage Forms and Strengths:

Tablets: 

• 50 mg niraparib/500 mg abiraterone acetate
• 100 mg niraparib/500 mg abiraterone acetate

Contraindications:

None.

Warnings and Precautions:

• Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): MDS/AML, including a case with fatal outcome, has been observed in patients treated with AKEEGA. Monitor patients for hematological toxicity and discontinue if MDS/AML is confirmed. 
• Myelosuppression: Test complete blood counts weekly for the first month, every two weeks for the next two months, monthly for the remainder of the first year, then every other month, and as clinically indicated. 
• Hypokalemia, Fluid Retention, and Cardiovascular Adverse Reactions: Monitor patients for hypertension, hypokalemia, and fluid retention at least weekly for the first two months, then once a month. Closely monitor patients whose underlying medical conditions might be compromised by increases in blood pressure, hypokalemia, or fluid retention. Control hypertension and correct hypokalemia before and during treatment with AKEEGA. 
• Hepatotoxicity: Can be severe and fatal. Monitor liver function and modify, interrupt, or discontinue treatment as recommended.
• Adrenocortical insufficiency: Monitor for symptoms and signs of adrenocortical insufficiency. Increased dosage of corticosteroids may be indicated before, during and after stressful situations. 
• Hypoglycemia: Severe hypoglycemia has been reported when abiraterone acetate, a component of AKEEGA, was administered to patients receiving medications containing thiazolidinediones (including pioglitazone) or repaglinide. Monitor blood glucose in patients with diabetes during and assess if antidiabetic agent dose modifications are required. 
• Increased fractures and mortality in combination with radium Ra 223 dichloride: Use of AKEEGA plus prednisone in combination with radium Ra 223 dichloride is not recommended. 
• Posterior Reversible Encephalopathy Syndrome (PRES):PRES has been observed in patients treated with niraparib, a component of AKEEGA. Discontinue AKEEGA if PRES is confirmed. 
• Embryo-Fetal Toxicity: AKEEGA can cause fetal harm. Advise males with female partners of reproductive potential to use effective contraception.

Adverse Reactions:

• The most common adverse reactions (≥20%), including laboratory abnormalities, are decreased hemoglobin, decreased lymphocytes, musculoskeletal pain, fatigue, decreased platelets, increased alkaline phosphatase, constipation, hypertension, nausea, decreased neutrophils, increased creatinine, increased potassium, decreased potassium, increased AST, fluid retention/edema, increased bilirubin, respiratory tract infection and arrhythmia.

Drug Interactions:

• Strong CYP3A4 Inducers: Avoid coadministration.
• CYP2D6 Substrates: Avoid coadministration of AKEEGA with CYP2D6 substrates for which minimal changes in concentration may lead to serious toxicities. If alternative treatments cannot be used, consider a dose reduction of the concomitantCYP2D6 substrate. 

Use in Specific Populations:

• Moderate or Severe Hepatic impairment: Avoid use.

Adapted From:

https://www.jnjlabels.com/package-insert/product-monograph/prescribing-information/AKEEGA-pi.pdf

 

Every health-care provider should make their own determination regarding specific safe and appropriate patient care practices, including drug dosages and indications. The provider should always consult the most recent prescribing/product information. FDA Focus information is not guaranteed to be accurate, complete, or current. JADPRO and its editors, authors, reviewers, and commentators cannot be held responsible for any liability incurred as a consequence of the application of any of the information listed within.