Dosing & Uses
Dosage Forms & Strengths
niraparib/abiraterone acetate
tablet
- 50mg/500mg
- 100mg/500mg
Prostate Cancer
Indicated with prednisone for adults with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC)
200 mg niraparib/1,000 mg abiraterone PO qDay, PLUS
Prednisone 10 mg PO qDay
Continue until disease progression or unacceptable toxicity
Patients should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy
Dosage Modifications
If toxicity is attributed to one component of the drug combination, the other component may be continued as a single agent at the current dose until the adverse reaction resolves and the drug combination can be resumed
Hemoglobin (Hgb) <8 g/dL
- Withhold for up to 28 days and monitor blood counts weekly until Hgb ≥9 g/dL
- Resume at reduced dose of 100 mg niraparib/1,000 mg abiraterone acetate PO qDay
- Monitor blood cell counts weekly for 28 days and as clinically indicated
-
Permanently discontinue
- If Hgb has not returned to acceptable levels within 28 days of dose interruption period
- If dose was already reduced to 100 mg niraparib/1,000 mg abiraterone PO qDay
- If myelodysplastic syndrome or acute myeloid leukemia (MDS/AML) confirmed
Platelet counts <100,000/mcL
-
First occurrence
- Withhold for up to 28 days and monitor blood counts weekly until platelet counts return to ≥100,000/mcL
- Resume at same or reduced dose of 100 mg niraparib/1,000 mg abiraterone qDay
- If platelet count <75,000/mcL, resume at reduced dose 100 mg niraparib/1,000 mg abiraterone qDay
Platelet counts <100,000/mcL
-
Second occurrence
- Withhold for up to 28 days and monitor blood counts weekly until platelet counts return to ≥100,000/mcL
- Resume at reduced dose of 100 mg niraparib/1,000 mg abiraterone qDay
- Permanently discontinue if platelet count has not returned to acceptable levels within 28 days of dose interruption period or if dose was already reduced to 100 mg niraparib/1,000 mg abiraterone PO qDay
Neutrophil <1,000/mcL
- Withhold and monitor blood counts weekly until neutrophil counts return to ≥1,500/mcL
- Resume at reduced dose of 100 mg niraparib/1,000 mg abiraterone qDay and monitor blood counts weekly for 28 days and as clinically indicated
-
Permanently discontinue
- If neutrophil count has not returned to acceptable levels within 28 days of dose interruption period
- If dose was already reduced to 100 mg niraparib/1,000 mg abiraterone PO qDay
Hematologic adverse reaction requiring transfusion
- Consider platelet transfusion for platelet count ≤10,000/mcL
- If there are other risk factors (eg, coadministration of anticoagulation or antiplatelet drugs), consider interrupting these drugs and/or transfusion at a higher platelet count
- Resume at reduced dose of 100 mg niraparib/1,000 mg abiraterone qDay
Hepatoxicity
- Defined as alanine transaminase (ALT) and/or aspartate transaminase (AST) >5x upper limit of normal (ULN) or total bilirubin >3x ULN
- Withhold and closely monitor liver function
- When AST and ALT resolves to ≤2.5x ULN and total bilirubin ≤1.5x ULN, may resume at reduced dose of 100 mg niraparib/500 mg abiraterone
- When resumed, monitor serum transaminases q2Weeks for 3 months, monthly thereafter, and as clinically indicated
-
Permanently discontinue
- If ALT/AST ≥20x ULN, or
- If ALT >3x ULN and total bilirubin >2x ULN in absence of biliary obstruction or other causes responsible for concurrent elevation, or
- Hepatotoxicity recurs at reduced dose of 100 mg niraparib/500 mg abiraterone
Other nonhematologic adverse reactions (Grade 3 or 4)
- Persistent despite medical management
- Withhold until resolution of adverse reaction or for up to 28 days
- If resolves in ≤28 days, may resume at reduced dose
- Permanently discontinue if adverse reaction(s) has not resolved after 28 days or Grade 3 or 4 adverse reaction recurs after dose reduction
- Discontinue if hypertensive crisis or other severe cardiovascular adverse reactions develop
Renal impairment
- Mild or moderate (CrCl 30-90 mL/min): No dosage adjustment necessary
- Severe (CrCl 15-30 mL/min): Monitor for increased adverse reactions and modify dosage as recommended for adverse reactions
Hepatic impairment
- Mild: No dosage adjustment necessary
- Moderate or severe: Avoid use
Dosing Considerations
Patient selection
- Select for treatment based on presence of a BRCA gene alteration (eg, FoundationOne CDx diagnostic companion test)
- Information on FDA-approved tests is available at: http://www.fda.gov/CompanionDiagnostics
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (2)
- mavacamten
abiraterone will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.
- ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)
abiraterone will increase the level or effect of ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) by decreasing metabolism. Contraindicated. Strong CYP2C8 inhibitors are shown to increase dasabuvir plasma concentrations (~10-fold), and therefore increase risk of QT prolongation
Serious - Use Alternative (11)
- apalutamide
apalutamide will decrease the level or effect of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.
- bosutinib
abiraterone increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- edoxaban
abiraterone will increase the level or effect of edoxaban by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Dose adjustment may be required with strong P-gp inhibitors. DVT/PE treatment: Decrease dose to 30 mg PO once daily. NVAF: No dose reduction recommended
- ivosidenib
ivosidenib will decrease the level or effect of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.
- metoclopramide intranasal
abiraterone will increase the level or effect of metoclopramide intranasal by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Concurrent use of metoclopramide intranasal and strong CYP2D6 inhibitors is not recommended since the metoclopramide intranasal dose cannot be adjusted.
- palifermin
palifermin increases toxicity of niraparib by Other (see comment). Avoid or Use Alternate Drug. Comment: Palifermin should not be administered within 24 hr before, during infusion of, or within 24 hr after administration of antineoplastic agents. Coadministration of palifermin within 24 hr of chemotherapy resulted in increased severity and duration of oral mucositis.
palifermin increases toxicity of abiraterone by Other (see comment). Avoid or Use Alternate Drug. Comment: Palifermin should not be administered within 24 hr before, during infusion of, or within 24 hr after administration of antineoplastic agents. Coadministration of palifermin within 24 hr of chemotherapy resulted in increased severity and duration of oral mucositis. - pomalidomide
abiraterone increases levels of pomalidomide by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- spironolactone
spironolactone increases toxicity of abiraterone by pharmacodynamic synergism. Contraindicated. Spironolactone binds to androgen receptor and may increase prostate-specific antigen (PSA) levels in abiraterone-treated prostate cancer patients.
- topotecan
abiraterone will increase the level or effect of topotecan by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Product labeling for PO topotecan recommends avoiding concomitant use of P-gp inhibitors; the interaction with IV topotecan may be less severe but is still likely of clinical significance
- tucatinib
abiraterone will increase the level or effect of tucatinib by Other (see comment). Avoid or Use Alternate Drug. Coadministration of tucatinib (a CYP2C8 substrate) with a strong or moderate CYP2C8 inhibitors increases tucatinib plasma concentrations and risk of toxicities.
- venetoclax
abiraterone will increase the level or effect of venetoclax by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If a P-gp inhibitor must be used, reduce the venetoclax dose by at least 50%. Monitor more closely for signs of venetoclax toxicities.
Monitor Closely (120)
- amitriptyline
abiraterone increases levels of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- amobarbital
amobarbital will decrease the level or effect of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- amoxapine
abiraterone increases levels of amoxapine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- apalutamide
abiraterone will increase the level or effect of apalutamide by Other (see comment). Use Caution/Monitor. Coadministration of apalutamide with strong CYP2C8 inhibitors does not require initial dosage modification; however, dose reduction may be needed based on tolerability.
- aripiprazole
abiraterone increases levels of aripiprazole by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- atomoxetine
abiraterone increases levels of atomoxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Reduced initial doses of atomoxetine are recommended with strong CYP2D6 inhibitors.
- belzutifan
belzutifan will decrease the level or effect of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.
- betaxolol
abiraterone increases levels of betaxolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- betrixaban
abiraterone increases levels of betrixaban by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Decrease betrixaban dose to 80 mg PO once, then 40 mg PO qDay if coadministered with a P-gp inhibitor.
- bosentan
bosentan decreases levels of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of abiraterone with strong CYP3A4 inducers; if a strong CYP3A4 inducer must be used, increase abiraterone dosage frequency from once daily to twice daily.
- butabarbital
butabarbital will decrease the level or effect of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- butalbital
butalbital will decrease the level or effect of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- cannabidiol
abiraterone will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP2C19 inhibitor.
- captopril
abiraterone increases levels of captopril by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- carbamazepine
carbamazepine decreases levels of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of abiraterone with strong CYP3A4 inducers; if a strong CYP3A4 inducer must be used, increase abiraterone dosage frequency from once daily to twice daily.
- carvedilol
abiraterone increases levels of carvedilol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- cenobamate
cenobamate will decrease the level or effect of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.
- ceritinib
abiraterone increases levels of ceritinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- chlordiazepoxide
abiraterone increases levels of chlordiazepoxide by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- chloroquine
abiraterone increases levels of chloroquine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- chlorpromazine
abiraterone increases levels of chlorpromazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- cinacalcet
abiraterone increases levels of cinacalcet by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- citalopram
abiraterone increases levels of citalopram by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- clobazam
abiraterone will increase the level or effect of clobazam by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Dosage adjustment may be required; CYP2C19 inhibitors may result in increased exposure to N-desmethylclobazam (active metabolite).
- clomipramine
abiraterone increases levels of clomipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- codeine
abiraterone increases levels of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- crizotinib
abiraterone increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution should be exercised with concomitant use of moderate CYP3A inhibitors. .
- dabigatran
abiraterone will increase the level or effect of dabigatran by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Atrial fibrillation: Avoid coadministering dabigatran with P-gp inhibitors if CrCl <30 mL/min. DVT/PE treatment: Avoid coadministering dabigatran with P-gp inhibitors if CrCl <50 mL/min
- dabrafenib
dabrafenib decreases levels of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of abiraterone with strong CYP3A4 inducers; if a strong CYP3A4 inducer must be used, increase abiraterone dosage frequency from once daily to twice daily.
- daprodustat
abiraterone will increase the level or effect of daprodustat by Other (see comment). Modify Therapy/Monitor Closely. Moderate CYP2C8 inhibitors increase daprodustat exposure. If coadministered with moderate CYP2C8 inhibitors, reduce daprodustat starting dose by half (except if starting dose is already 1 mg). Monitor hemoglobin and adjust daprodustat dose when initiating or stopping therapy with moderate CYP2C8 inhibitors during treatment
- desipramine
abiraterone increases levels of desipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- deutetrabenazine
abiraterone will increase the level or effect of deutetrabenazine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Strong CYP2D6 inhibitors increase the systemic exposure to the active dihydro-metabolites of deutetrabenazine by approximately 3-fold. Do not exceed 18 mg/dose and 36 mg/day of deutetrabenazine if coadministered with strong CYP2D6 inhibitors.
- dexamethasone
dexamethasone decreases levels of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of abiraterone with strong CYP3A4 inducers; if a strong CYP3A4 inducer must be used, increase abiraterone dosage frequency from once daily to twice daily.
- dextroamphetamine transdermal
abiraterone will increase the level or effect of dextroamphetamine transdermal by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during dextroamphetamine initiation and after a dosage increase. If serotonin syndrome occurs, discontinue dextroamphetamine transdermal and CYP2D6 inhibitor.
- dextromethorphan
abiraterone increases levels of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- diazepam intranasal
abiraterone will increase the level or effect of diazepam intranasal by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Strong or moderate CYP2C19 inhibitors may decrease rate of diazepam elimination, thereby increasing adverse reactions to diazepam.
- dichlorphenamide
dichlorphenamide and abiraterone both decrease serum potassium. Use Caution/Monitor.
- doxepin
abiraterone increases levels of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- doxepin cream
abiraterone increases levels of doxepin cream by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- doxorubicin
abiraterone increases levels of doxorubicin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- doxorubicin liposomal
abiraterone increases levels of doxorubicin liposomal by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- duloxetine
abiraterone increases levels of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- efavirenz
efavirenz decreases levels of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of abiraterone with strong CYP3A4 inducers; if a strong CYP3A4 inducer must be used, increase abiraterone dosage frequency from once daily to twice daily.
- elagolix
elagolix will decrease the level or effect of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.
- eluxadoline
abiraterone increases levels of eluxadoline by decreasing metabolism. Use Caution/Monitor. As a precautionary measure due to incomplete information on the metabolism of eluxadoline, use caution when coadministered with strong CYP2C8 inhibitors.
- encorafenib
encorafenib, abiraterone. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.
- enzalutamide
enzalutamide decreases levels of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of abiraterone with strong CYP3A4 inducers; if a strong CYP3A4 inducer must be used, increase abiraterone dosage frequency from once daily to twice daily.
- eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of abiraterone with strong CYP3A4 inducers; if a strong CYP3A4 inducer must be used, increase abiraterone dosage frequency from once daily to twice daily
- etravirine
etravirine decreases levels of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of abiraterone with strong CYP3A4 inducers; if a strong CYP3A4 inducer must be used, increase abiraterone dosage frequency from once daily to twice daily.
- flecainide
abiraterone increases levels of flecainide by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- flotufolastat F 18
abiraterone, flotufolastat F 18. Other (see comment). Use Caution/Monitor. Comment: Androgen deprivation therapy (ADT) and other therapies targeting the androgen pathway (eg, androgen receptor antagonists) can result in changes in uptake of flotufolastat F 18 in prostate cancer. Effects of these therapies on performance of flotufolastat F 18 PET has not been established.
- fluoxetine
abiraterone increases levels of fluoxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- fluphenazine
abiraterone increases levels of fluphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- fluvoxamine
abiraterone will increase the level or effect of fluvoxamine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. If therapy cannot be avoided, exercise caution and consider a dose reduction of CYP2D6 substrate
- fosphenytoin
fosphenytoin decreases levels of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of abiraterone with strong CYP3A4 inducers; if a strong CYP3A4 inducer must be used, increase abiraterone dosage frequency from once daily to twice daily.
- gallium Ga 68 PSMA-11
abiraterone will decrease the level or effect of gallium Ga 68 PSMA-11 by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Androgen deprivation therapy and other therapies targeting the androgen pathway may result in changes in the uptake of gallium Ga 68 PSMA-11 in prostate cancer. The effect of ADT on the performance of gallium Ga 68 PSMA-11 is unknown.
- glecaprevir/pibrentasvir
abiraterone will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- haloperidol
abiraterone increases levels of haloperidol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- ifosfamide
abiraterone will decrease the level or effect of ifosfamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Use of a CYP3A4 inhibitor may decrease metabolism of ifosfamide, potentially reducing ifosfamide therapeutic effects.
- iloperidone
abiraterone increases levels of iloperidone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- imipramine
abiraterone increases levels of imipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- indacaterol, inhaled
indacaterol, inhaled, abiraterone. QTc interval. Use Caution/Monitor. Drugs that are known to prolong the QTc interval may have an increased the risk of ventricular arrhythmias.
- ivosidenib
abiraterone will increase the level or effect of ivosidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with moderate CYP3A4 inhibitors may increase ivosidenib plasma concentrations, thus increasing the risk of QTc prolongation. Monitor for increased risk of QTc interval prolongation.
- lenacapavir
lenacapavir will increase the level or effect of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.
- lofexidine
abiraterone will increase the level or effect of lofexidine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Concomitant use of lofexidine with strong CYP2D6 inhibitors may increase lofexidine plasma levels. Monitor for symptoms of orthostasis and bradycardia if coadministered with a CYP2D6 inhibitor. Consider lofexidine dose reduction.
- lorlatinib
lorlatinib will decrease the level or effect of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- maprotiline
abiraterone increases levels of maprotiline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- metaxalone
abiraterone increases levels of metaxalone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- methamphetamine
abiraterone increases levels of methamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- methohexital
methohexital will decrease the level or effect of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- metoprolol
abiraterone increases levels of metoprolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- mexiletine
abiraterone increases levels of mexiletine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- mirtazapine
abiraterone increases levels of mirtazapine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- mitotane
mitotane decreases levels of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.
- nafcillin
nafcillin decreases levels of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of abiraterone with strong CYP3A4 inducers; if a strong CYP3A4 inducer must be used, increase abiraterone dosage frequency from once daily to twice daily.
- naldemedine
abiraterone increases levels of naldemedine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor naldemedine for potential adverse effects if coadministered with P-gp inhibitors.
- nebivolol
abiraterone increases levels of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- nevirapine
nevirapine decreases levels of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of abiraterone with strong CYP3A4 inducers; if a strong CYP3A4 inducer must be used, increase abiraterone dosage frequency from once daily to twice daily.
- nintedanib
abiraterone increases levels of nintedanib by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. If nintedanib adverse effects occur, management may require interruption, dose reduction, or discontinuation of therapy .
- nortriptyline
abiraterone increases levels of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- oliceridine
abiraterone will increase the level or effect of oliceridine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. If concomitant use is necessary, may require less frequent oliceridine dosing. Closely monitor for respiratory depression and sedation and titrate subsequent doses accordingly. If inhibitor is discontinued, consider increase oliceridine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.
- olodaterol inhaled
abiraterone and olodaterol inhaled both increase QTc interval. Use Caution/Monitor. Drugs that prolong the QTc interval and may potentiate the effects of beta2 agonists on the cardiovascular system; increased risk of ventricular arrhythmias
- oxaliplatin
oxaliplatin and niraparib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Use of oxaliplatin with concomitant immunosuppressants or with impaired immune systems may increased risk for serious infections.
- oxcarbazepine
oxcarbazepine decreases levels of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of abiraterone with strong CYP3A4 inducers; if a strong CYP3A4 inducer must be used, increase abiraterone dosage frequency from once daily to twice daily.
- paroxetine
abiraterone increases levels of paroxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- pentobarbital
pentobarbital will decrease the level or effect of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- perphenazine
abiraterone increases levels of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- phenobarbital
phenobarbital decreases levels of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of abiraterone with strong CYP3A4 inducers; if a strong CYP3A4 inducer must be used, increase abiraterone dosage frequency from once daily to twice daily.
- phenytoin
phenytoin decreases levels of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of abiraterone with strong CYP3A4 inducers; if a strong CYP3A4 inducer must be used, increase abiraterone dosage frequency from once daily to twice daily.
- pindolol
abiraterone increases levels of pindolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- pitolisant
abiraterone will increase the level or effect of pitolisant by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. If coadministered with strong CYP2D6 inhibitors, initiate pitolisant at 8.9 mg/day and increase after 7 days to maximum of 17.8 mg/day. For patients currently taking pitolisant, reduce pitolisant dose by half upon initiating strong CYP2D6 inhibitors.
- primidone
primidone decreases levels of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of abiraterone with strong CYP3A4 inducers; if a strong CYP3A4 inducer must be used, increase abiraterone dosage frequency from once daily to twice daily.
- procainamide
abiraterone increases levels of procainamide by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- promethazine
abiraterone increases levels of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- propafenone
abiraterone increases levels of propafenone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- propranolol
abiraterone increases levels of propranolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- protriptyline
abiraterone increases levels of protriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- rifabutin
rifabutin decreases levels of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of abiraterone with strong CYP3A4 inducers; if a strong CYP3A4 inducer must be used, increase abiraterone dosage frequency from once daily to twice daily.
- rifampin
rifampin decreases levels of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of abiraterone with strong CYP3A4 inducers; if a strong CYP3A4 inducer must be used, increase abiraterone dosage frequency from once daily to twice daily.
- rifapentine
rifapentine decreases levels of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of abiraterone with strong CYP3A4 inducers; if a strong CYP3A4 inducer must be used, increase abiraterone dosage frequency from once daily to twice daily.
- rifaximin
abiraterone increases levels of rifaximin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- risperidone
abiraterone increases levels of risperidone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- secobarbital
secobarbital will decrease the level or effect of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- selexipag
abiraterone will increase the level or effect of selexipag by decreasing metabolism. Modify Therapy/Monitor Closely. Reduce selexipag dose to once daily if coadministered with moderate CYP2C8 inhibitors.
- sertraline
abiraterone increases levels of sertraline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- siponimod
siponimod and abiraterone both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.
siponimod and niraparib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects. - St John's Wort
St John's Wort decreases levels of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of abiraterone with strong CYP3A4 inducers; if a strong CYP3A4 inducer must be used, increase abiraterone dosage frequency from once daily to twice daily.
- stiripentol
stiripentol, abiraterone. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.
- tamoxifen
abiraterone, tamoxifen. affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. CYP2D6 inhibition decreases metabolism of tamoxifen to hydroxytamoxifen, and N-desmethyl tamoxifen to endoxifen (active metabolites with 100-fold greater affinity for estrogen receptor); decreased endoxifen levels may result in poor clinical outcome.
- tamsulosin
abiraterone increases levels of tamsulosin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- tazemetostat
tazemetostat will decrease the level or effect of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tecovirimat
tecovirimat will decrease the level or effect of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.
- teniposide
abiraterone will increase the level or effect of teniposide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- tetrabenazine
abiraterone increases levels of tetrabenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- thioridazine
abiraterone increases levels of thioridazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- tolterodine
abiraterone increases levels of tolterodine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- tramadol
abiraterone increases levels of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider increasing tramadol dose if clinically appropriate; if abiraterone is discontinued, consider reducing tramadol dose and frequently monitor for signs of respiratory depression and sedation.
- trimipramine
abiraterone increases levels of trimipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- vemurafenib
abiraterone increases levels of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- venlafaxine
abiraterone increases levels of venlafaxine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
Minor (4)
- acetazolamide
acetazolamide will increase the level or effect of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- anastrozole
anastrozole will increase the level or effect of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- cyclophosphamide
cyclophosphamide will increase the level or effect of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- larotrectinib
larotrectinib will increase the level or effect of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
Adverse Effects
>10%
All grades
- Hemoglobin decreased (67%)
- Lymphocytes decreased (55%)
- White blood cell (WBC) decreased (48%)
- Musculoskeletal pain (44%)
- Fatigue (43%)
- Platelets decreased (37%)
- Constipation (34%)
- Alkaline phosphatase (ALP) increased (34%)
- Hypertension (33%)
- Nausea (33%)
- Neutrophils decreased (32%)
- Creatinine increased (30%)
- Potassium increased (25%)
- Potassium decreased (20%)
- AST increased (20%)
- ALT increased (18%)
- Edema (17%)
- Dyspnea (15%)
- Decreased appetite (15%)
- Vomiting (15%)
- Dizziness (14%)
- Abdominal pain (12%)
- Hemorrhage (12%)
- Headache (12%)
- Urinary tract infection (12%)
- Cough (12%)
- Insomnia (12%)
- Bilirubin increased (12%)
Grade 3 or 4
- Hemoglobin decreased (26%)
- Lymphocytes decreased (22%)
- Hypertension (14%)
1-10%
Rash (7%)
ALT increased (5%)
AST increased (5%)
Cerebrovascular accident (4.4%)
Pulmonary embolism (2.7%)
Deep vein thrombosis (2.7%)
Acute kidney injury (2.7%)
All grades
- Weight decreased (10%)
- Arrhythmia (10%)
- Fall (10%)
- Pyrexia (10%)
Grade 3 or 4
- Platelets decreased (8%)
- Neutrophils decreased (7%)
- WBC decreased (6%)
- Fatigue (5%)
- Potassium decreased (5%)
- Musculoskeletal pain (4%)
- Urinary tract infection (3%)
- Decreased appetite (2%)
- Abdominal pain (2%)
- Hemorrhage (2%)
- Arrhythmia (2%)
- Pyrexia (2%)
- ALP increased (1.8%)
- AST increased (1.8%)
- Constipation (1%)
- Nausea (1%)
- Dyspnea (1%)
- Headache (1%)
- Weight decreased (1%)
- Fall (1%)
<1%
Grade 3 or 4
- Potassium increased (0.9%)
- ALT increased (0.9%)
Warnings
Contraindications
None
Cautions
Hepatotoxicity in patients receiving abiraterone acetate has been reported; safety in patients with moderate or severe hepatic impairment has not been established; promptly measure serum total bilirubin, AST, and ALT if clinical symptoms or signs suggestive of hepatotoxicity develop
Adrenocortical insufficiency has been reported in clinical trials in patients receiving abiraterone in combination with prednisone, following interruption of daily steroids and/or with concurrent infection or stress; monitor for symptoms and signs of adrenocortical insufficiency, particularly if patients have been withdrawn from prednisone, have prednisone dose reductions, or experience unusual stress
If clinically indicated, perform appropriate tests to confirm diagnosis of adrenocortical insufficiency
May cause hypoglycemia in patients being treated with other medications for diabetes
Severe hypoglycemia has been reported when abiraterone was administered to patients receiving medications containing thiazolidinediones (including pioglitazone) or repaglinide
Monitor blood glucose in patients with diabetes during and after discontinuation of treatment; assess if antidiabetic drug dosage needs to be adjusted to minimize risk
Niraparib/abiraterone with prednisone is not recommended for use in combination with Ra-223 dichloride outside of clinical trials
Posterior reversible encephalopathy syndrome (PRES) has been observed in patients treated with niraparib as a single agent; monitor for signs and symptoms of PRES; if PRES is suspected, promptly discontinue, and administer appropriate treatment
Based on animal reproductive studies and mechanism of action, may cause fetal harm and loss of pregnancy when administered to pregnant females
Females who are or may become pregnant should handle tablets with protection (eg, gloves)
Myelodysplastic syndrome/acute myeloid leukemia
- MDS/AML, including cases with fatal outcome, has been observed
- For suspected MDS/AML or prolonged hematologic toxicities, refer to a hematologist for further evaluation
- Discontinue if MDS/AML is confirmed
Myelosuppression
- May cause myelosuppression (anemia, thrombocytopenia, or neutropenia)
- Monitor complete blood cell counts weekly during first month of treatment, q2Weeks for the next 3months, monthly for the remainder of the first year and then every other month, and as clinically indicated
- Do not start niraparib/abiraterone until patients have adequately recovered from hematologic toxicity caused by previous therapy
- If hematologic toxicities do not resolve within 28 days following interruption, discontinue and refer to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics
Hypokalemia, fluid retention, and cardiovascular adverse reactions
- May cause hypokalemia and fluid retention because of increased mineralocorticoid levels resulting from CYP17 inhibition
- In postmarketing experience, QT interval prolongation and torsades de pointes have been observed in patients who develop hypokalemia while taking abiraterone
- Hypertension and hypertensive crisis have also been reported
- Safety in patients with New York Heart Association (NYHA) Class II to IV heart failure has not been established
- Monitor for hypertension, hypokalemia, and fluid retention at least weekly for the first 2 months, then once a month
- Closely monitor patients whose underlying medical conditions might be compromised by increases in blood pressure, hypokalemia, or fluid retention, such as those with heart failure, recent myocardial infarction, cardiovascular disease, or ventricular arrhythmia
- Control hypertension and correct hypokalemia before and during treatment
- Discontinue in patients who develop hypertensive crisis or other severe cardiovascular adverse reactions
Drug interaction overview
- Abiraterone: CYP3A4 substrate, CYP2D6 moderate inhibitor, CYP2C8 inhibitor
-
Strong CYP3A4 inducers
- Avoid coadministration
- Strong CYP3A4 inducers may decrease abiraterone concentrations, leading to decreased efficacy
-
Sensitive CYP2D6 substrates
- Avoid coadministration unless otherwise recommended in prescribing information for CYP2D6 substrates for which minimal changes in concentration may lead to serious toxicities
- If unavoidable, consider reducing dose of CYP2D6 substrate
- Abiraterone increases concentration of CYP2D6 substrates, which may increase risk of adverse reactions of substrates
-
Sensitive CYP2C8 substrates
- Monitor for signs of toxicity related to a CYP2C8 substrate for which a minimal change in plasma concentration may lead to serious or life-threatening adverse reactions
- Abiraterone increases concentration of CYP2C8 substrates, which may increase risk of adverse reactions of substrates
Pregnancy & Lactation
Pregnancy
Based on findings from animal studies and mechanism of action, abiraterone can cause fetal harm and potential loss of pregnancy
Niraparib has the potential to cause teratogenicity and/or embryofetal death since niraparib is genotoxic and targets actively dividing cells in animals and patients (eg, bone marrow)
There are no human data regarding use in pregnant females
Animal data
- Due to potential risk to a fetus based on its mechanism of action, animal developmental and reproductive toxicology studies were not conducted with niraparib
- Oral administration of abiraterone acetate to pregnant rats during organogenesis caused adverse developmental effects at maternal exposures ~≥0.03x the human exposure (AUC) at the recommended dose
Contraception
- Advise patients with female partners of reproductive potential to use effective contraception during treatment and for 4 months after last dose
Infertility
- Based on animal studies, may impair reproductive function and fertility in males of reproductive potential
Lactation
Safety and efficacy not established in females
There is no information available on presence of niraparib or abiraterone in human milk, or on effects on breastfed children or milk production
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Niraparib
- Poly (ADP-ribose) polymerase (PARP) inhibitor; niraparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes, resulting in DNA damage, apoptosis, and cell death
Abiraterone
- Androgen biosynthesis inhibitor that inhibits 17 alpha-hydroxylase/C17, 20-lyase (CYP17); this enzyme is expressed in testicular, adrenal, and prostatic tumor tissues and is required for androgen biosynthesis
- Inhibition of CYP17 by abiraterone can also result in increased mineralocorticoid production by the adrenal glands
Absorption
Peak plasma concentration
- Niraparib: 831 ng/mL (steady-state)
- Abiraterone: 151 ng/mL (steady-state)
AUC
- Niraparib: 13,616 ng⋅hr/mL (steady-state)
- Abiraterone: 707 ng⋅hr/mL (steady-state)
Peak plasma time
- Niraparib: 3 hr
- Abiraterone: 1.5 hr
Distribution
Vd
- Niraparib: 1,117 L
- Abiraterone: 25,774 L
Protein bound
- Niraparib: 83% to human plasma proteins
- Abiraterone: >99% to human plasma proteins, albumin, and alpha-1 acid glycoprotein
Metabolism
Niraparib: Metabolized by carboxylesterases
Abiraterone acetate
- Rapidly converted in vivo to abiraterone
- Metabolized by CYP3A4 and SULT2A1
Elimination
Half-life
- Niraparib: 62 hr
- Abiraterone: 20 hr
Clearance
- Niraparib: 16.7 L/hr
- Abiraterone: 1673 L/hr
Excretion
- Niraparib: 48% (urine [11% unchanged]); 39% (feces [19% unchanged])
- Abiraterone: 88% (feces); 5% (urine)
Administration
Oral Administration
Take on an empty stomach
Do not eat food 2 hr before and 1 hr after administration
Swallow tablets whole with water; do not break, crush, or chew
Missed dose
- Instruct patient to take missed dose as soon as possible on the same day and resume next dose at normal schedule the following day
Storage
Tablets: Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)
Images
Formulary
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