Niraparib-Abiraterone

Niraparib-Abiraterone is a combination medication used with prednisone for the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC).

• Niraparib-Abiraterone is available under the following different brand names: Akeega

Common side effects of Niraparib-Abiraterone include:

• musculoskeletal pain
• fatigue
• constipation
• high blood pressure (hypertension)
• nausea
• fluid retention (edema)
• shortness of breath
• decreased appetite
• vomiting
• dizziness
• COVID-19
• headache
• abdominal pain
• bleeding
• urinary tract infection
• cough
• insomnia
• weight loss
• irregular heartbeats (arrhythmia)
• falls
• fever
• decreased hemoglobin
• decreased white blood cells
• decreased platelets
• increased alkaline phosphatase
• increased creatinine
• increased or decreased potassium
• increased AST levels
• increased ALT levels
• increased bilirubin

Serious side effects of Niraparib-Abiraterone include:

• anemia
• high blood pressure
• thrombocytopenia
• neutropenia
• increase levels of the liver enzyme alkaline phosphatase
• liver problems
• adrenal problems
• low blood sugar (hypoglycemia)
• posterior reversible encephalopathy syndrome (PRES)

Rare side effects of Niraparib-Abiraterone include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 50 mg/500 mg
• 100 mg/500 mg

Prostate cancer

Adult dosage

• 200 mg niraparib/1000 mg abiraterone orally once a day, plus
• Prednisone 10 mg orally once a day
• Continue until disease progression or unacceptable toxicity
• Patients should also receive a gonadotropin-releasing hormone analog concurrently or should have had bilateral orchiectomy

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Niraparib-Abiraterone has severe interactions with the following drugs:
  • mavacamten
  • ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)
• Niraparib-Abiraterone has serious interactions with the following drugs:
  • apalutamide
  • bosutinib
  • edoxaban
  • ivosidenib
  • metoclopramide intranasal
  • palifermin
  • pomalidomide
  • spironolactone
  • topotecan
  • tucatinib
  • venetoclax
• Niraparib-Abiraterone has moderate interactions with at least 120 other drugs
• Niraparib-Abiraterone has minor interactions with the following drugs:
  • acetazolamide
  • anastrozole
  • cyclophosphamide
  • larotrectinib

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Niraparib-Abiraterone?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Niraparib-Abiraterone?”

Cautions

• Hepatotoxicity in patients receiving abiraterone acetate has been reported; safety in patients with moderate or severe hepatic impairment has not been established; promptly measure serum total bilirubin, AST, and ALT if clinical symptoms or signs suggestive of hepatotoxicity develop
• Adrenocortical insufficiency has been reported in clinical trials in patients receiving abiraterone in combination with prednisone, following interruption of daily steroids and/or with concurrent infection or stress; monitor for symptoms and signs of adrenocortical insufficiency, particularly if patients have been withdrawn from prednisone, have prednisone dose reductions, or experience unusual stress
• If clinically indicated, perform appropriate tests to confirm the diagnosis of adrenocortical insufficiency
• May cause hypoglycemia in patients being treated with other medications for diabetes
• Severe hypoglycemia has been reported when abiraterone was administered to patients receiving medications containing thiazolidinediones (including pioglitazone) or repaglinide
• Monitor blood glucose in patients with diabetes during and after discontinuation of treatment; assess if antidiabetic drug dosage needs to be adjusted to minimize risk
• Niraparib-Abiraterone with prednisone is not recommended for use in combination with Ra-223 dichloride outside of clinical trials
• Posterior reversible encephalopathy syndrome (PRES) has been observed in patients treated with niraparib as a single agent; monitor for signs and symptoms of PRES; if PRES is suspected, promptly discontinue the drug, and administer appropriate treatment
• Based on animal reproductive studies and the drug’s mechanism of action, Niraparib-Abiraterone may cause fetal harm and loss of pregnancy when administered to pregnant women
• Women who are or may become pregnant should handle tablets with protection (eg, gloves)
• Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
  • MDS/AML, including cases with fatal outcomes, has been observed
  • For suspected MDS/AML or prolonged hematologic toxicities, refer to a hematologist for further evaluation
  • Discontinue if MDS/AML is confirmed
• Myelosuppression
  • May cause myelosuppression (anemia, thrombocytopenia, or neutropenia)
  • Monitor complete blood cell counts weekly during the first month of treatment, every 2 weeks for the next 3 months, monthly for the remainder of the first year, and then every other month, and as clinically indicated
  • Do not start Niraparib-Abiraterone until patients have adequately recovered from hematologic toxicity caused by previous therapy
  • If hematologic toxicities do not resolve within 28 days following the interruption of the drug, discontinue and refer to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics
• Hypokalemia, fluid retention, and cardiovascular adverse reactions
  • May cause hypokalemia and fluid retention because of increased mineralocorticoid levels resulting from CYP17 inhibition
  • In postmarketing experience, QT interval prolongation and torsades de pointes have been observed in patients who develop hypokalemia while taking abiraterone
• Hypertension and hypertensive crisis have also been reported
  • Safety in patients with New York Heart Association Class II to IV heart failure has not been established
  • Monitor for hypertension, hypokalemia, and fluid retention at least weekly for the first 2 months, then once a month
  • Closely monitor patients whose underlying medical conditions (such as heart failure, recent myocardial infarction, cardiovascular disease, or ventricular arrhythmia) might be compromised by increases in blood pressure, hypokalemia, or fluid retention
  • Control hypertension and correct hypokalemia before and during treatment
  • Discontinue in patients who develop hypertensive crisis or other severe cardiovascular adverse reactions
• Drug interaction overview
  • Abiraterone: CYP3A4 substrate, CYP2D6 moderate inhibitor, CYP2C8 inhibitor
  • Strong CYP3A4 inducers
    • Avoid coadministration
  • Strong CYP3A4 inducers may decrease abiraterone concentrations, leading to decreased efficacy
  • Sensitive CYP2D6 substrates
    • Avoid coadministration unless otherwise recommended in prescribing information for CYP2D6 substrates for which minimal changes in concentration may lead to serious toxicities
    • If unavoidable, consider reducing the dose of CYP2D6 substrate
    • Abiraterone increases the concentration of CYP2D6 substrates, which may increase the risk of adverse reactions of substrates
  • Sensitive CYP2C8 substrates
    • Monitor for signs of toxicity related to a CYP2C8 substrate for which a minimal change in plasma concentration may lead to serious or life-threatening adverse reactions
    • Abiraterone increases the concentration of CYP2C8 substrates, which may increase the risk for adverse reactions of substrates

Pregnancy and Lactation

• Based on findings from animal studies and the drug’s mechanism of action, abiraterone can cause fetal harm and potential loss of pregnancy
• Niraparib has the potential to cause teratogenicity and/or embryofetal death since niraparib is genotoxic and targets actively dividing cells into animals and patients (eg, bone marrow)
• There are no human data regarding use in pregnant women
• Contraception
  • Advise patients with women partners of reproductive potential to use effective contraception during treatment and for 4 months after the last dose
• Infertility
  • Based on animal studies, may impair reproductive function and fertility in males of reproductive potential
• Lactation
  • Safety and efficacy not established in women
  • There is no information available on the presence of Niraparib or Abiraterone in human milk, or its effects on breastfed children or milk production