Version May 2024
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 labeling.
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): $375.00
100-500 mg (per each): $375.00
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 acetate: Hazardous agent (NIOSH 2016 [group 1]).
Niraparib: This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Niraparib may cause carcinogenicity, teratogenicity, reproductive toxicity, and genotoxicity.
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 2016; USP-NF 2020).
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.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its lists of drug classes which have a heightened risk of causing significant patient harm when used in error.
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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Ajmaline: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Ajmaline. Risk C: Monitor therapy
Amitriptyline: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Amitriptyline. CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Amitriptyline. Risk C: Monitor therapy
Amoxapine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Amoxapine. Risk C: Monitor therapy
Amphetamines: CYP2D6 Inhibitors (Moderate) may increase the 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 therapy
Androgens: Hypertension-Associated Agents may enhance the hypertensive effect of Androgens. Risk C: Monitor therapy
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Apalutamide: May enhance the adverse/toxic effect of Niraparib. Apalutamide may decrease the 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: CYP2D6 Inhibitors (Moderate) may increase the 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 therapy
ARIPiprazole Lauroxil: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of ARIPiprazole Lauroxil. Risk C: Monitor therapy
Atomoxetine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Atomoxetine. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brexpiprazole: CYP2D6 Inhibitors (Moderate) may increase the 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 therapy
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Carvedilol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Carvedilol. Risk C: Monitor therapy
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Choline C 11: Antiandrogens may diminish the therapeutic effect of Choline C 11. Risk C: Monitor therapy
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
ClomiPRAMINE: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of ClomiPRAMINE. CYP2D6 Inhibitors (Moderate) may increase the serum concentration of ClomiPRAMINE. Risk C: Monitor therapy
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
CloZAPine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. 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 diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk C: Monitor therapy
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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 diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Abiraterone Acetate. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Abiraterone Acetate. Management: Avoid when possible. If the combination cannot be avoided, increase abiraterone acetate dosing frequency from once daily to twice daily during combined use. Reduce abiraterone dose back to the prior dose and frequency once strong inducer is discontinued. Risk D: Consider therapy modification
Daprodustat: CYP2C8 Inhibitors (Weak) may increase the serum concentration of Daprodustat. Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect 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 enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect 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 the serum concentration of Desipramine. Risk C: Monitor therapy
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Deutetrabenazine: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Deutetrabenazine. Risk C: Monitor therapy
Dextromethorphan: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Dextromethorphan. Risk C: Monitor therapy
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Doxepin (Systemic): CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Doxepin (Systemic). Risk C: Monitor therapy
Doxepin (Topical): CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Doxepin (Topical). Risk C: Monitor therapy
DOXOrubicin (Conventional): CYP2D6 Inhibitors (Moderate) may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
Eliglustat: CYP2D6 Inhibitors (Moderate) may increase the 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 enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Flecainide: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Flecainide. Risk C: Monitor therapy
Flotufolastat F18: Antiandrogens may diminish the diagnostic effect of Flotufolastat F18. 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 diminish the therapeutic effect 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 the serum concentration of Haloperidol. Risk C: Monitor therapy
HMG-CoA Reductase Inhibitors (Statins): Abiraterone Acetate may enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Iboga: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Iboga. Risk C: Monitor therapy
Iloperidone: CYP2D6 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P95 may be decreased. CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P88 may be increased. CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Iloperidone. Risk C: Monitor therapy
Imipramine: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Imipramine. Concentrations of desipramine may be increased. CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Imipramine. Risk C: Monitor therapy
Indium 111 Capromab Pendetide: Antiandrogens may diminish the diagnostic effect of Indium 111 Capromab Pendetide. Risk X: Avoid combination
Indoramin: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Indoramin. Risk C: Monitor therapy
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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 enhance the immunosuppressive effect 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
Lofepramine: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Lofepramine. The active metabolite of lofepramine is desipramine. Risk C: Monitor therapy
Mequitazine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Mequitazine. Risk X: Avoid combination
Methadone: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Methadone. Risk C: Monitor therapy
Metoclopramide: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Metoclopramide. Risk C: Monitor therapy
Metoprolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Metoprolol. Risk C: Monitor therapy
Mumps- Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Nebivolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nebivolol. Risk C: Monitor therapy
Nortriptyline: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nortriptyline. Risk C: Monitor therapy
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Oliceridine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Oliceridine. Risk C: Monitor therapy
Olmutinib: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Olmutinib. Risk C: Monitor therapy
PARoxetine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of PARoxetine. Risk C: Monitor therapy
Perhexiline: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Perhexiline. Risk C: Monitor therapy
Perphenazine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Perphenazine. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Piflufolastat F18: Antiandrogens may diminish the diagnostic effect of Piflufolastat F18. 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 enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Pimozide: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Pimozide. Risk C: Monitor therapy
Pitolisant: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Pitolisant. Risk C: Monitor therapy
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to 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 enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Propafenone: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Propafenone. Risk C: Monitor therapy
Propranolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Propranolol. Risk C: Monitor therapy
Protriptyline: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Protriptyline. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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 enhance the adverse/toxic effect of Abiraterone Acetate. Specifically, the risk for fractures and death may be increased. Risk X: Avoid combination
Repaglinide: CYP2C8 Inhibitors (Weak) may increase the serum concentration of Repaglinide. Risk C: Monitor therapy
Rifabutin: May decrease the serum concentration of Abiraterone Acetate. Risk C: Monitor therapy
Rifapentine: May decrease the serum concentration of Abiraterone Acetate. Risk C: Monitor therapy
RisperiDONE: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of RisperiDONE. Risk C: Monitor therapy
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect 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 enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sertindole: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Sertindole. Risk C: Monitor therapy
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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
Solriamfetol: May enhance the hypertensive effect of Hypertension-Associated Agents. Risk C: Monitor therapy
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy
Spironolactone: May diminish the therapeutic effect 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 enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect 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 combination
Tamoxifen: CYP2D6 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) 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 the serum concentration of Tamsulosin. Risk C: Monitor therapy
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tetrabenazine: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Risk C: Monitor therapy
Thiazolidinediones: Abiraterone Acetate may enhance the hypoglycemic effect of Thiazolidinediones. Risk C: Monitor therapy
Thioridazine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Thioridazine. Risk X: Avoid combination
Timolol (Systemic): CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Timolol (Systemic). Risk C: Monitor therapy
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
TraMADol: CYP2D6 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of TraMADol. CYP2D6 Inhibitors (Moderate) may increase the serum concentration of TraMADol. Risk C: Monitor therapy
Trimipramine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Trimipramine. Risk C: Monitor therapy
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Valbenazine: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Valbenazine. Risk C: Monitor therapy
Vortioxetine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Vortioxetine. Risk C: Monitor therapy
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Zuclopenthixol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Zuclopenthixol. Risk C: Monitor therapy
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.
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