Version July 2025
Note: Do not initiate niraparib/abiraterone acetate until after adequately recovered from hematologic toxicity due to previous therapy. Control hypertension and correct hypokalemia prior to and during niraparib/abiraterone acetate treatment.
Prostate cancer, metastatic, castration resistant, BRCA mutated: Oral: Niraparib 200 mg/abiraterone acetate 1,000 mg once daily (in combination with prednisone); continue until disease progression or unacceptable toxicity (Ref). Note: Patients receiving niraparib/abiraterone acetate should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently (or should have had a bilateral orchiectomy).
Missed doses: If a dose is missed, administer the dose as soon as possible on the same day and resume the next dose at the regularly scheduled time on the next day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl 15 to <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Monitor for increased adverse reactions and modify dosage as recommended for adverse reactions.
Initial dose with preexisting liver cirrhosis :
Mild impairment (Child-Turcotte-Pugh class A): No dosage adjustment necessary.
Moderate or severe impairment (Child-Turcotte-Pugh class B, C): Avoid niraparib/abiraterone acetate use.
Dosage adjustment for hepatotoxicity during treatment:
ALT and/or AST >5 times ULN or total bilirubin >3 times ULN: Withhold niraparib/abiraterone acetate and closely monitor liver function. When AST and ALT resolve to ≤2.5 times ULN and total bilirubin is ≤1.5 times ULN, may resume at a reduced dose of niraparib 100 mg/abiraterone acetate 500 mg once daily with serum transaminase monitoring every 2 weeks for 3 months, then monthly thereafter (and as clinically indicated).
Concurrent elevation of ALT >3 times ULN and total bilirubin >2 times ULN in the absence of biliary obstruction or other causes responsible for the concurrent elevation: Permanently discontinue niraparib/abiraterone acetate.
ALT or AST ≥20 times ULN at any time: Permanently discontinue niraparib/abiraterone acetate.
Recurrent hepatotoxicity at a dose of niraparib 100 mg/abiraterone acetate 500 mg: Permanently discontinue niraparib/abiraterone acetate.
Note: Do not reinitiate niraparib/abiraterone acetate until toxicity has resolved to ≤ grade 1. If the toxicity is attributed to one component of niraparib/abiraterone acetate, the other component may be continued (as a single agent) at the current dose until the adverse reaction resolves and niraparib/abiraterone acetate can be resumed. See "Dosage Modification" table.
|
Adverse reaction |
Severity |
Niraparib dosage modification |
|---|---|---|
|
a MDS = myelodysplastic syndrome; AML = acute myeloid leukemia; PRES = posterior reversible encephalopathy syndrome. | ||
|
Hematologic toxicity | ||
|
Anemia |
Hemoglobin <8 g/dL |
Withhold niraparib/abiraterone acetate and monitor blood counts weekly. When hemoglobin is ≥9 g/dL, resume at a reduced dose of niraparib 100 mg/abiraterone acetate 1,000 mg once daily and monitor blood counts weekly for 28 days or as clinically indicated. Permanently discontinue niraparib/abiraterone acetate if hemoglobin has not returned to acceptable levels within 28 days of interrupting the dose, or if dose has already been reduced to niraparib 100 mg/abiraterone acetate 1,000 mg once daily. |
|
Neutropenia |
Neutrophils <1,000/mm3 |
Withhold niraparib/abiraterone acetate and monitor blood counts weekly. When neutrophils are ≥1,500/mm3, resume at a reduced dose of niraparib 100 mg/abiraterone acetate 1,000 mg once daily and monitor blood counts weekly for 28 days or as clinically indicated. Permanently discontinue niraparib/abiraterone acetate if neutrophils have not returned to acceptable levels within 28 days of interrupting the dose, or if dose has already been reduced to niraparib 100 mg/abiraterone acetate 1,000 mg once daily. |
|
Thrombocytopenia |
Platelets <100,000/mm3 |
First occurrence: Withhold niraparib/abiraterone acetate for a maximum of 28 days and monitor blood counts weekly. When platelets are ≥100,000/mm3, resume at the same dose or at a reduced dose of niraparib 100 mg/abiraterone acetate 1,000 mg once daily. If platelet count was <75,000/mm3, resume at reduced dose of niraparib 100 mg/abiraterone acetate 1,000 mg once daily. Second occurrence: Withhold niraparib/abiraterone acetate for a maximum of 28 days and monitor blood counts weekly. When platelets are ≥100,000/mm3, resume at reduced dose of niraparib 100 mg/abiraterone acetate 1,000 mg once daily. Permanently discontinue niraparib/abiraterone acetate if platelet count has not returned to acceptable levels within 28 days of interrupting dose, or if dose has already been reduced to niraparib 100 mg/abiraterone acetate 1,000 mg once daily. |
|
Hematologic toxicity |
Transfusion dependence |
Withhold niraparib/abiraterone acetate; resume at a reduced dose of niraparib 100 mg/abiraterone acetate 1,000 mg once daily. Consider platelet transfusion for platelets ≤10,000/mm3. If other risk factors (eg, concurrent anticoagulation or antiplatelet therapy), consider interrupting the anticoagulant/antiplatelet therapy and/or transfusing to a higher platelet count. |
|
Persistent (>28 days following treatment interruption) |
Permanently discontinue niraparib/abiraterone acetate. Obtain consult with hematology for further assessment, including bone marrow and cytogenetic analysis. | |
|
Secondary MDS or AML |
Suspected |
Refer to a hematologist for further evaluation if MDS/AML is suspected. |
|
Confirmed |
Permanently discontinue niraparib/abiraterone acetate. | |
|
Nonhematologic toxicity | ||
|
Adrenocortical insufficiency |
Any |
Increased doses of corticosteroids may be indicated before, during, and after stressful situations. |
|
Cardiovascular adverse reactions |
Severe |
Permanently discontinue niraparib/abiraterone acetate. |
|
Hypertensive crisis |
Any |
Permanently discontinue niraparib/abiraterone acetate. |
|
PRES |
Suspected |
Permanently discontinue niraparib/abiraterone acetate. Manage appropriately if suspected; the safety of reinitiating niraparib/abiraterone in patients previously experiencing PRES is not known. |
|
Other treatment-related adverse reaction that persist despite medical management |
Grade 3 or 4 |
Withhold niraparib/abiraterone acetate for a maximum of 28 days or until resolution. If resolves in ≤28 days, resume niraparib/abiraterone at a reduced dose. Permanently discontinue niraparib/abiraterone acetate if adverse reaction(s) has not resolved after 28 days or for recurrent grade 3 or 4 adverse reaction after dose reduction. |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults receiving concomitant prednisone.
>10%:
Cardiovascular: Edema (17%), hypertension (33%)
Endocrine & metabolic: Decreased serum potassium (20%), increased serum potassium (25%)
Gastrointestinal: Abdominal pain (12%), constipation (34%), decreased appetite (15%), nausea (33%), vomiting (15%)
Genitourinary: Urinary tract infection (12%)
Hematologic & oncologic: Anemia (67%; grades 3/4: 26% to 28%), decreased white blood cell count (48%; grades 3/4: 6%), hemorrhage (4% to 12%; grade 3/4: 2%), lymphocytopenia (55%; grades 3/4: 22%), neutropenia (32%; grades 3/4: 7%), thrombocytopenia (37%; grades 3/4: 8%)
Hepatic: Increased serum alanine aminotransferase (5% to 18%), increased serum alkaline phosphatase (34%), increased serum aspartate aminotransferase (5% to 20%), increased serum bilirubin (12%)
Nervous system: Dizziness (14%), fatigue (43%), headache (12%), insomnia (12%)
Neuromuscular & skeletal: Musculoskeletal pain (44%)
Renal: Increased serum creatinine (30%)
Respiratory: Cough (12%), dyspnea (15%)
1% to 10%:
Cardiovascular: Cardiac arrhythmia (10%), deep vein thrombosis (3%), pulmonary embolism (3%)
Dermatologic: Skin rash (7%)
Endocrine & metabolic: Weight loss (10%)
Nervous system: Cerebrovascular accident (4%), falling (10%)
Renal: Acute kidney injury (3%)
Respiratory: Pneumonia (4%)
Miscellaneous: Fever (10%)
Frequency not defined:
Genitourinary: Hematuria
Nervous system: Asthenia
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to niraparib, abiraterone acetate, or any component of the formulation.
Concerns related to adverse effects:
• Adrenocortical insufficiency: Niraparib/abiraterone acetate may cause adrenal insufficiency; adrenocortical insufficiency has been reported with abiraterone acetate (in combination with prednisone), following interruption of daily corticosteroids and/or with concurrent infection or stress. The risk for adrenocortical insufficiency may be increased if prednisone is withdrawn, with prednisone dose reductions, or with unusual stress. Signs/symptoms of adrenocortical insufficiency may be masked by adverse reactions associated with mineralocorticoid excess. If clinically indicated, perform appropriate tests to confirm the diagnosis of adrenocortical insufficiency. Increased doses of corticosteroids may be indicated before, during, and after stressful situations.
• Bone marrow suppression: Niraparib/abiraterone acetate may cause myelosuppression (anemia, thrombocytopenia, or neutropenia), including grade 3 and 4 events. Some patients required red blood cell transfusions, while some patients required multiple transfusions. A small percentage of patients required discontinuation due to anemia. Prolonged hematologic toxicity may require hematology evaluation for bone marrow analysis and cytogenetics.
• Cardiovascular effects: Niraparib/abiraterone acetate may cause hypokalemia and fluid retention as a consequence of increased mineralocorticoid levels due to CYP17 inhibition. QT prolongation and torsades de pointes have been observed in patients who develop abiraterone-associated hypokalemia. Hypertension and hypertensive crisis have also been reported with niraparib. In a cohort of the clinical study that used prednisone 10 mg/day in combination with niraparib/abiraterone acetate, grades 3 to 4 hypokalemia were reported in a small percentage of patients in the niraparib/abiraterone acetate arm; grades 3 to 4 hypertension were also observed in the niraparib/abiraterone acetate arm. Patients with New York Heart Association class II to IV heart failure were excluded from the clinical trial and safety has not been established in these patients. Patients with underlying medical conditions (eg, heart failure, recent myocardial infarction, cardiovascular disease, or ventricular arrhythmia) could be compromised by increases in BP, hypokalemia, or fluid retention.
• Hepatotoxicity: Niraparib/abiraterone acetate may cause hepatotoxicity. Hepatotoxicity has been reported with abiraterone acetate; may be severe, including fulminant hepatitis, acute liver failure, and deaths. Grade 3 or 4 ALT or AST elevations have been reported in a small percentage of patients. Patients with moderate or severe hepatic impairment were excluded from the clinical trial and the safety of niraparib/abiraterone acetate in these patients has not been established.
• Hypoglycemia: Niraparib/abiraterone acetate may cause hypoglycemia in patients being treated with other medications for diabetes; severe hypoglycemia has been reported when abiraterone acetate is administered to patients also receiving medications containing thiazolidinediones (including pioglitazone) or repaglinide. Assess if antidiabetic therapy needs to be adjusted to minimize the risk of hypoglycemia.
• Posterior reversible encephalopathy syndrome: Niraparib/abiraterone acetate may cause posterior reversible encephalopathy syndrome (PRES). PRES has been observed with niraparib (as a single agent) at doses higher than the recommended dose of niraparib/abiraterone acetate.
• Secondary malignancy: Niraparib/abiraterone acetate may cause myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), including cases with fatal outcome. MDS/AML has been observed with niraparib; all patients who developed treatment-related secondary MDS/AML had received prior chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy. Refer to a hematologist for further evaluation if MDS/AML is suspected and/or for prolonged hematological toxicities.
Concurrent drug therapy issues:
• Radium Ra 223 dichloride: Due to an increase in the incidence of fractures and a risk for mortality, niraparib/abiraterone (with prednisone) is not recommended for use in combination with Ra-223 dichloride outside of a clinical trial. Subsequent treatment with Ra-223 should not be initiated for at least 5 days after the last niraparib/abiraterone acetate (with prednisone) dose.
Other warnings/precautions:
• Appropriate use: Select patients for therapy based on the presence of deleterious or suspected deleterious BRCA mutation. Information on approved tests may be found at http://www.fda.gov/companiondiagnostics.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Akeega: Abiraterone acetate 500 mg and niraparib tosylate 50 mg, Abiraterone acetate 500 mg and niraparib tosylate 100 mg
No
Tablets (Akeega Oral)
50-500 mg (per each): $382.50
100-500 mg (per each): $382.50
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Akeega: Abiraterone acetate 500 mg and niraparib tosylate 50 mg, Abiraterone acetate 500 mg and niraparib tosylate 100 mg
Oral: Administer on an empty stomach, at least 1 hour before and 2 hours after food (per the manufacturer); no food should be consumed for at least 2 hours before or for at least 1 hour after the dose. Swallow tablets whole with water. Do not break, crush, or chew.
Caregivers who are or could become pregnant should wear gloves when handling niraparib/abiraterone acetate.
Abiraterone is a hazardous agent (NIOSH 2024 [table 2]); niraparib is not on the NIOSH (2024) list; however, it may meet the criteria for a hazardous drug.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Prostate cancer, metastatic, castration resistant, BRCA-mutated: Treatment of deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC) (in combination with prednisone) in adults. Select patients for therapy based on an approved test.
Niraparib/abiraterone acetate may be confused with abiraterone, niraparib.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care Settings).
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Ajmaline: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Ajmaline. Risk C: Monitor
Amitriptyline: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Amitriptyline. CYP2D6 Inhibitors (Moderate) may increase active metabolite exposure of Amitriptyline. Risk C: Monitor
Amoxapine: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Amoxapine. Risk C: Monitor
Amphetamines: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Amphetamines. Management: Monitor for amphetamine toxicities (including serotonin syndrome) if used with a moderate CYP2D6 inhibitor. Initiate amphetamine therapy at lower doses, monitor frequently, and adjust doses as needed. Discontinue amphetamines if serotoinin syndrome occurs Risk C: Monitor
Androgens: Hypertension-Associated Agents may increase hypertensive effects of Androgens. Risk C: Monitor
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Apalutamide: May increase adverse/toxic effects of Niraparib. Apalutamide may decrease serum concentration of Niraparib. Management: Consider alternatives to this combination when possible. If combined, monitor for decreased niraparib concentrations and efficacy, as well as for increased niraparib toxicities. Risk D: Consider Therapy Modification
ARIPiprazole Lauroxil: CYP2D6 Inhibitors (Moderate) may increase active metabolite exposure of ARIPiprazole Lauroxil. Risk C: Monitor
ARIPiprazole: CYP2D6 Inhibitors (Moderate) may increase serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy, indication, or dosage form. Consult full interaction monograph for specific recommendations. Risk C: Monitor
Atomoxetine: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Atomoxetine. Risk C: Monitor
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of BCG Products. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Brexpiprazole: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Brexpiprazole. Management: If brexpiprazole is to be used together with both a moderate CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor, the brexpiprazole dose should be reduced to 25% of the usual dose when treating indications other than major depressive disorder. Risk C: Monitor
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Carvedilol: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Carvedilol. Risk C: Monitor
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Choline C 11: Antiandrogens may decrease therapeutic effects of Choline C 11. Risk C: Monitor
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
ClomiPRAMINE: CYP2D6 Inhibitors (Moderate) may increase serum concentration of ClomiPRAMINE. CYP2D6 Inhibitors (Moderate) may increase active metabolite exposure of ClomiPRAMINE. Risk C: Monitor
CloZAPine: CYP2D6 Inhibitors (Moderate) may increase serum concentration of CloZAPine. Risk C: Monitor
CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Miscellaneous Oncologic Agents) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
Codeine: CYP2D6 Inhibitors (Moderate) may decrease therapeutic effects of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk C: Monitor
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease serum concentration of Abiraterone Acetate. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Abiraterone Acetate. Management: Avoid coadministration with strong CYP3A4 inducers. For patients treated with single-agent abiraterone who require therapy with a strong CYP3A4 inducers, abiraterone frequency may increased to twice daily. See full mono for details. Risk D: Consider Therapy Modification
Daprodustat: CYP2C8 Inhibitors (Weak) may increase serum concentration of Daprodustat. Risk C: Monitor
Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Desipramine: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Desipramine. Risk C: Monitor
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Deutetrabenazine: CYP2D6 Inhibitors (Moderate) may increase active metabolite exposure of Deutetrabenazine. Risk C: Monitor
Dextromethorphan: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Dextromethorphan. Risk C: Monitor
Doxepin (Systemic): CYP2D6 Inhibitors (Moderate) may increase serum concentration of Doxepin (Systemic). Risk C: Monitor
Doxepin (Topical): CYP2D6 Inhibitors (Moderate) may increase serum concentration of Doxepin (Topical). Risk C: Monitor
DOXOrubicin (Conventional): CYP2D6 Inhibitors (Moderate) may increase serum concentration of DOXOrubicin (Conventional). Risk X: Avoid
Eliglustat: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Eliglustat. Management: Eliglustat dose is 84 mg daily with CYP2D6 inhibitors. Use is contraindicated (COI) when also combined with strong CYP3A4 inhibitors. When also combined with a moderate CYP3A4 inhibitor, use is COI in CYP2D6 EMs or IMs and should be avoided in CYP2D6 PMs. Risk D: Consider Therapy Modification
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Flecainide: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Flecainide. Risk C: Monitor
Flotufolastat F18: Coadministration of Antiandrogens and Flotufolastat F18 may alter diagnostic results. Management: Therapies targeting the androgen pathway may result in changes in the uptake of flotufolastat F18 in prostate cancer. The impact of these therapies on the performance of flotufolastat F18 is unknown; consider use of alternative agents. Risk D: Consider Therapy Modification
Gallium Ga 68 PSMA-11: Antiandrogens may decrease therapeutic effects of Gallium Ga 68 PSMA-11. Management: Therapies targeting the androgen pathway may result in changes in the uptake of gallium Ga 68 PSMA-11 (gozetotide) in prostate cancer. The impact on the performance of gallium Ga 68 PSMA-11 (gozetotide) is unknown; consider use of alternative agents. Risk D: Consider Therapy Modification
Haloperidol: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Haloperidol. Risk C: Monitor
HMG-CoA Reductase Inhibitors (Statins): Abiraterone Acetate may increase myopathic (rhabdomyolysis) effects of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor
Iboga: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Iboga. Risk C: Monitor
Iloperidone: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Iloperidone. CYP2D6 Inhibitors (Moderate) may decrease active metabolite exposure of Iloperidone. Specifically, concentrations of the metabolite P95 may be decreased. CYP2D6 Inhibitors (Moderate) may increase active metabolite exposure of Iloperidone. Specifically, concentrations of the metabolite P88 may be increased. Risk C: Monitor
Imipramine: CYP2D6 Inhibitors (Moderate) may increase active metabolite exposure of Imipramine. Concentrations of desipramine may be increased. CYP2D6 Inhibitors (Moderate) may increase serum concentration of Imipramine. Risk C: Monitor
Indium 111 Capromab Pendetide: Coadministration of Antiandrogens and Indium 111 Capromab Pendetide may alter diagnostic results. Risk X: Avoid
Indoramin: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Indoramin. Risk C: Monitor
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider Therapy Modification
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Lofepramine: CYP2D6 Inhibitors (Moderate) may increase active metabolite exposure of Lofepramine. The active metabolite of lofepramine is desipramine. Risk C: Monitor
Mequitazine: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Mequitazine. Risk X: Avoid
Methadone: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Methadone. Risk C: Monitor
Metoclopramide: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Metoclopramide. Risk C: Monitor
Metoprolol: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Metoprolol. Risk C: Monitor
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Mumps- Rubella- or Varicella-Containing Live Vaccines may increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Nebivolol: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Nebivolol. Risk C: Monitor
Nortriptyline: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Nortriptyline. Risk C: Monitor
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor
Oliceridine: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Oliceridine. Risk C: Monitor
Olmutinib: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Olmutinib. Risk C: Monitor
PARoxetine: CYP2D6 Inhibitors (Moderate) may increase serum concentration of PARoxetine. Risk C: Monitor
Perhexiline: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Perhexiline. Risk C: Monitor
Perphenazine: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Perphenazine. Risk C: Monitor
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Piflufolastat F18: Coadministration of Antiandrogens and Piflufolastat F18 may alter diagnostic results. Management: Therapies targeting the androgen pathway may result in changes in the uptake of piflufolastat F18 in prostate cancer. The impact of these therapies on the performance of piflufolastat F18 is unknown; consider use of alternative agents. Risk D: Consider Therapy Modification
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Pimozide: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Pimozide. Risk C: Monitor
Pitolisant: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Pitolisant. Risk C: Monitor
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Propafenone: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Propafenone. Risk C: Monitor
Propranolol: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Propranolol. Risk C: Monitor
Protriptyline: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Protriptyline. Risk C: Monitor
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Radium Ra 223 Dichloride: May increase adverse/toxic effects of Abiraterone Acetate. Specifically, the risk for fractures and death may be increased. Risk X: Avoid
Repaglinide: CYP2C8 Inhibitors (Weak) may increase serum concentration of Repaglinide. Risk C: Monitor
Rifabutin: May decrease serum concentration of Abiraterone Acetate. Risk C: Monitor
Rifapentine: May decrease serum concentration of Abiraterone Acetate. Risk C: Monitor
RisperiDONE: CYP2D6 Inhibitors (Moderate) may increase serum concentration of RisperiDONE. Risk C: Monitor
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sertindole: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Sertindole. Risk C: Monitor
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Sofpironium: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Sofpironium. Risk C: Monitor
Solriamfetol: May increase hypertensive effects of Hypertension-Associated Agents. Risk C: Monitor
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor
Spironolactone: May decrease therapeutic effects of Abiraterone Acetate. Management: Consider alternatives to the combined use of spironolactone and abiraterone. If combined, monitor the clinical response to abiraterone closely, looking specifically for signs of clinical failure and/or disease progression. Risk D: Consider Therapy Modification
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Tamoxifen: CYP2D6 Inhibitors (Moderate) may decrease active metabolite exposure of Tamoxifen. Specifically, CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites. Management: Consider alternatives to the use of moderate CYP2D6 inhibitors with tamoxifen when possible, as the combination may be associated with reduced clinical effectiveness of tamoxifen. Risk D: Consider Therapy Modification
Tamsulosin: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Tamsulosin. Risk C: Monitor
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tetrabenazine: CYP2D6 Inhibitors (Moderate) may increase active metabolite exposure of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Risk C: Monitor
Thiazolidinediones: Abiraterone Acetate may increase hypoglycemic effects of Thiazolidinediones. Risk C: Monitor
Thioridazine: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Thioridazine. Risk X: Avoid
Timolol (Systemic): CYP2D6 Inhibitors (Moderate) may increase serum concentration of Timolol (Systemic). Risk C: Monitor
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
TraMADol: CYP2D6 Inhibitors (Moderate) may increase serum concentration of TraMADol. CYP2D6 Inhibitors (Moderate) may decrease active metabolite exposure of TraMADol. Risk C: Monitor
Trimipramine: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Trimipramine. Risk C: Monitor
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before or during therapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Valbenazine: CYP2D6 Inhibitors (Moderate) may increase active metabolite exposure of Valbenazine. Risk C: Monitor
Vortioxetine: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Vortioxetine. Risk C: Monitor
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Zuclopenthixol: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Zuclopenthixol. Risk C: Monitor
Administration of abiraterone acetate with food results in up to a 10-fold increase in AUC and up to a 17-fold increase in Cmax, depending on the fat content of the meal (compared with administration in a fasted state). Management: Do not administer niraparib/abiraterone acetate with food; administer on an empty stomach, at least 1 hour before and 2 hours after food.
Patients with partners who could become pregnant should use effective contraception during therapy and for 4 months after the last dose of niraparib/abiraterone acetate.
The manufacturer recommends caregivers who are or could become pregnant wear gloves when handling niraparib/abiraterone acetate tablets.
Based on data from animal reproduction studies, in utero exposure to niraparib/abiraterone acetate may cause fetal harm.
It is not known if niraparib or abiraterone acetate are present in breast milk.
CBC (monitor weekly during the first month of niraparib/abiraterone acetate treatment, every 2 weeks for the next 2 months, monthly for the remainder of the first year, and then every other month and as clinically indicated; monitor weekly if hematologic toxicity occurs). Prolonged hematologic toxicity may require hematology evaluation for bone marrow analysis and cytogenetics. Monitor serum transaminases (ALT and AST) and bilirubin levels prior to treatment initiation, every 2 weeks for the first 3 months, then monthly thereafter (monitor more frequently if elevations occur); if clinical symptoms or signs suggestive of hepatotoxicity develop, promptly assess serum total bilirubin, AST, and ALT, and monitor every 2 weeks for 3 months, then monthly thereafter (and as clinically indicated). Monitor serum potassium (baseline, at least weekly for the first 2 months, then monthly). Monitor blood glucose (in patients with diabetes) during treatment and after discontinuation. Assess antidiabetic therapy (in patients with diabetes) for possible dosage adjustments to minimize the risk for hypoglycemia. Monitor BP (at least weekly for the first 2 months, then monthly). Monitor for signs/symptoms of fluid retention (at least weekly for the first 2 months, then monthly). Closely monitor for hypertension, hypokalemia, and fluid retention in patients with underlying medical conditions (eg, heart failure, recent myocardial infarction, cardiovascular disease, or ventricular arrhythmia). Monitor for signs/symptoms of adrenocortical insufficiency, particularly if prednisone is withdrawn, with prednisone dose reductions, or with unusual stress. Monitor for signs/symptoms of hepatotoxicity, hypoglycemia, posterior reversible encephalopathy syndrome, and /or secondary malignancy. Monitor adherence.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Niraparib is a poly (ADP-ribose) polymerase (PARP) enzyme inhibitor, including PARP-1 and PARP-2. PARP-1 and PARP-2 are involved in DNA repair. Inhibiting PARP enzymatic activity forms PARP-DNA complexes that result in DNA damage, apoptosis, and cell death. Niraparib induces cytotoxicity in tumor cell lines with and without BRCA1/2 deficiencies.
Abiraterone acetate is converted to abiraterone, which is an androgen biosynthesis inhibitor. Abiraterone inhibits CYP17 (17 alpha-hydroxylase/C17,20-lyase), an enzyme required for androgen biosynthesis, which is expressed in testicular, adrenal, and prostatic tumor tissues. It inhibits the formation of the testosterone precursors dehydroepiandrosterone (DHEA) and androstenedione.
Distribution: Niraparib: 1,117 L; Abiraterone: 25,774 L.
Protein binding: Niraparib: 83% (to plasma proteins); Abiraterone: >99% (to plasma proteins and alpha-1 acid glycoprotein).
Metabolism: Niraparib: Metabolized by carboxylesterases; Abiraterone acetate: Rapidly converted in vivo to abiraterone and further metabolized via CYP3A4 and SULT2A1.
Bioavailability: Niraparib: ~73%; Abiraterone acetate: Systemic exposure is increased by food.
Half-life elimination: Niraparib: ~62 hours; Abiraterone: ~20 hours.
Time to peak: Niraparib: 3 hours; Abiraterone: 1.5 hours.
Excretion: Niraparib: Urine (~48%; 11% as unchanged drug); feces (~39%; 19% as unchanged drug); Abiraterone: Feces (~88%; 55% as abiraterone acetate and 22% as abiraterone); urine (~5%).
Clearance: Niraparib: 16.7 L/hour; Abiraterone: 1,637 L/hour.
Hepatic function impairment: Moderate hepatic impairment (total bilirubin >1.5 to 3 times ULN and any AST) increased niraparib AUC by 56%, compared to normal hepatic function. Mild hepatic impairment (Child-Turcotte-Pugh class A) increased the abiraterone AUC by 1.1-fold and moderate hepatic impairment (Child-Turcotte-Pugh class B) increased the abiraterone AUC by 3.6-fold, compared to normal hepatic function. Severe hepatic impairment (Child-Turcotte-Pugh class C) increased abiraterone AUC by 7-fold and the fraction of free drug increased by 2-fold, compared to normal hepatic function.
