Abiraterone / Niraparib Dosage

Medically reviewed by Drugs.com. Last updated on Nov 7, 2023.

Usual Adult Dose for Prostate Cancer

Recommended dose: Niraparib 200 mg-abiraterone acetate 1000 mg orally once a day in combination with prednisone 10 mg orally once a day
Duration of therapy: Until disease progression or unacceptable toxicity

Patients receiving this drug should also receive concurrent treatment with a gonadotropin-releasing hormone analog or should have had bilateral orchiectomy.

Comments:

• Select patients for treatment based on the presence of a BRCA gene alteration.
• For adverse reactions, consider interruption of treatment, dose reduction, or dose discontinuation.

Use: For the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated metastatic castration-resistant prostate cancer.

• Select patients for therapy based on an FDA-approved test for this drug.

Renal Dose Adjustments

Mild to Moderate Renal Dysfunction: No adjustment recommended
Severe Renal Dysfunction:

• Use with caution as treatment in this population has not been studied.
• Monitor patients with severe renal dysfunction for increased adverse reactions and modify dosage as recommended for adverse reactions.

Liver Dose Adjustments

Mild Liver Dysfunction: No dosage adjustment recommended
Moderate to Severe Liver Dysfunction: Avoid use

Dose Adjustments

Dosage Modifications for Adverse Reactions:
MYELOSUPPRESSION:
Hemoglobin Less Than 8 g/dL:

• Withhold therapy and monitor blood counts weekly.
• When hemoglobin increases to 9 g/dL or greater, resume therapy at a reduced dose of niraparib 100 mg-abiraterone acetate 1000 mg once daily and monitor blood counts weekly for 28 days and as indicated.
• Permanently discontinue therapy if hemoglobin has not returned to acceptable levels within 28 days after dose interruption or if patient has already undergone a dose reduction.

Platelet Count Less Than 100,000/mcL (First Occurrence):

• Withhold therapy for a maximum of 28 days and monitor blood counts weekly until platelets return to 100,000/mcL or greater.
• Resume therapy at same dose or at a reduced dose of niraparib 100 mg-abiraterone acetate 1000 mg once daily.
• If platelet count is less than 75,000/mcL resume at a reduced dose of niraparib 100 mg-abiraterone acetate 1000 mg once daily.

Platelet Count Less Than 100,000/mcL (Second Occurrence):

• Withhold therapy for a maximum of 28 days and monitor blood counts weekly until platelets are greater 100,000/mcL or greater.
• Resume therapy at a reduced dose of niraparib 100 mg-abiraterone acetate 1000 mg once daily.
• Permanently discontinue therapy if platelet count has not returned to acceptable levels within 28 days after dose interruption or if patient has already undergone a dose reduction.
• If myelodysplastic syndrome or acute myeloid leukemia (MDS/AML) is confirmed, discontinue treatment.

Neurophil Count Less Than 1000/mcL:

• Withhold therapy and monitor blood counts weekly.
• When neutrophil count returns to 1500/mcL or greater, resume therapy at a reduced dose of niraparib 100 mg-abiraterone acetate 1000 mg once daily and monitor blood counts weekly for 28 days and as indicated.
• Permanently discontinue therapy if neutrophils have not returned to acceptable levels within 28 days after dose interruption or if patient has already undergone a dose reduction.

Hematologic Adverse Reaction Requiring Transfusion:

• Consider platelet transfusion if platelet count is 10,000/mcL or less.
• 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 therapy at a reduced dose of niraparib 100 mg-abiraterone acetate 1000 mg once daily.

HEPATOTOXICITY
ALT and/or AST greater than 5 times the upper limit of normal (5 x ULN) or total bilirubin greater than 3 × ULN:

• Withhold therapy and closely monitor liver function.
• Permanently discontinue therapy if:
• ALT or AST is 20 x ULN or greater, OR
• ALT is greater than 3 x ULN and total bilirubin is greater than 2 x ULN in the absence of biliary obstruction or other causes responsible for the concurrent elevation, OR
• Hepatotoxicity recurs at the reduced dose of niraparib 100 mg-abiraterone acetate 500 mg once daily
• When AST and ALT resolves to 2.5 x ULN or less and total bilirubin is 1.5 X ULN or less, therapy may be resumed at the reduced dose of niraparib 100 mg-abiraterone acetate 500 mg once daily.
• After resuming, 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 Reactions:

• Withhold therapy until resolution of adverse reaction or for a maximum of 28 days.
• If reaction resolution occurs in 28 days or less, therapy may be resumed at the reduced dose.
• Permanently discontinue treatment if adverse reaction(s) has not resolved after 28 days or Grade 3 or 4 adverse reaction reoccurs after dose reduction.
• Discontinue therapy in patients who develop hypertensive crisis or other severe cardiovascular adverse reactions.

Precautions

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Take on an empty stomach; instruct patient to avoid eating 2 hours before and 1 hour after taking this drug.
• Do not break, crush, or chew tablets.
• Females who are pregnant or may become pregnant should handle tablets with protection.
• Missed 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.

Storage requirements:

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

General:

• Do not start therapy with this drug in patients who have not adequately recovered from hematologic toxicity caused by previous treatments.

Monitoring:

• Cardiovascular: Closely monitor patients with underlying cardiovascular conditions. Screen patients for increased blood pressure, hypertension, or hypertensive crisis during therapy. Monitor patients for hypertension at least weekly for the first two months, then once a month.
• Endocrine: Evaluate for symptoms and signs of adrenocortical insufficiency during therapy, particularly if patients are withdrawn from prednisone, have prednisone dose reductions, or experience unusual stress.
• Hematologic: Monitor complete blood counts weekly during the first month of treatment, every two weeks for the next two months, monthly for the remainder of the first year and then every other month, and as clinically indicated.
• Hepatic: Measure serum transaminases (ALT/AST) and bilirubin levels prior to starting treatment, every two weeks for the first three months of treatment, and then monthly thereafter.
• Metabolic: Assess for fluid retention and hypokalemia at least weekly for the first

two months, then once a month; untreated hypokalemia has been associated with adverse cardiovascular outcomes. Monitor blood glucose in patients with diabetes during and after discontinuation of treatment.

• Neurologic: Assess for signs and symptoms of posterior reversible encephalopathy syndrome during therapy.

Patient advice:

• Read the FDA-approved patient labeling (Patient Information).
• Instruct patients to take this drug orally once daily on an empty stomach with prednisone daily and to not interrupt doses without prior consultation with healthcare provider.
• Inform patients taking concurrent gonadotropin-releasing hormone analog therapy to maintain this treatment during the course of therapy with this drug.
• Advise patients that periodic monitoring of their blood counts is recommended.
• Inform patients to contact their healthcare provider for new onset of pallor, weakness, dyspnea, fatigue, bleeding, fever, or symptoms of infection.
• Encourage patients to adhere to corticosteroids and to report symptoms of hypokalemia or edema to their healthcare provider.
• Alert patients to immediately report symptoms of hepatotoxicity to their healthcare provider.
• Advise diabetic patients to monitor blood glucose during and after discontinuation of treatment.
• Inform patients to report symptoms of adrenocortical insufficiency.
• Educate patients on the signs and symptoms of posterior reversible encephalopathy syndrome that can present with seizure, headaches, altered mental status, or vision changes.
• Counsel patients that this drug may harm a developing fetus and/or cause pregnancy loss; females who are pregnant or may become pregnant should handle tablets with protection.
• Counsel males with female partners of reproductive potential to use effective contraception during treatment and for 4 months after the last dose.

See also:

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer