ZYTIGA

Cytostatic Androgen Biosynthesis Inhibitors

Hazardous Drugs Classification
NIOSH 2016 List: Group 1
NIOSH (Draft) 2020 List: Table 2
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs. Cutting, crushing, or otherwise manipulating tablets will increase exposure.
The manufacturer of Yonsa advises that women who are pregnant or who may become pregnant should not touch abiraterone.
The manufacturer of Zytiga advises that women who are pregnant or who may become pregnant should not touch abiraterone without protection, such as gloves.[44156]

Oral Administration Oral Solid Formulations

To avoid overdose, be aware that abiraterone (Yonsa) has different dosing and food effects than abiraterone (Zytiga).
Administer whole; have patient swallow tablets intact with water.[44156] [63206]
Abiraterone (Zytiga) must be taken on an empty stomach, at least 1 hour before or 2 hours after a meal.[44156]
Abiraterone (Yonsa) must be taken as a single dose once daily with or without food.[63206]
If a dose of either abiraterone or prednisone/methylprednisolone is missed, take your prescribed dose the next day. Tell your health care provider right away if you miss more than one dose.

Severe

hypertension / Early / 1.3-20.0
hypokalemia / Delayed / 2.8-10.0
lymphopenia / Delayed / 4.1-8.7
hypophosphatemia / Delayed / 0-7.2
hyperglycemia / Delayed / 0-6.5
elevated hepatic enzymes / Delayed / 1.4-6.4
bone fractures / Delayed / 0-5.9
arthralgia / Delayed / 2.0-4.2
hypernatremia / Delayed / 0-4.0
myalgia / Early / 0-3.0
dyspnea / Early / 0-2.4
fatigue / Early / 0-2.2
edema / Delayed / 0.4-1.9
heart failure / Delayed / 1.3-1.9
hematuria / Delayed / 0-1.3
diarrhea / Early / 0.6-0.9
fever / Early / 0-0.6
chest pain (unspecified) / Early / 0-0.5
constipation / Delayed / 0-0.4
hypertriglyceridemia / Delayed / 0-0.4
hot flashes / Early / 0.2-0.3
cardiac arrest / Early / 0-0.3
respiratory arrest / Rapid / 0-0.3
increased urinary frequency / Early / 0-0.3
headache / Early / 0-0.3
hyperbilirubinemia / Delayed / 0.1-0.2
infection / Delayed / 0-0.2
insomnia / Early / 0-0.2
hepatic failure / Delayed / Incidence not known
hepatotoxicity / Delayed / Incidence not known
rhabdomyolysis / Delayed / Incidence not known
musculoskeletal pain / Early / Incidence not known
supraventricular tachycardia (SVT) / Early / Incidence not known
atrial fibrillation / Early / Incidence not known
bradycardia / Rapid / Incidence not known
atrial tachycardia / Early / Incidence not known
AV block / Early / Incidence not known
atrial flutter / Early / Incidence not known
cardiomyopathy / Delayed / Incidence not known
torsade de pointes / Rapid / Incidence not known
ventricular tachycardia / Early / Incidence not known
angioedema / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known

Moderate

adrenocortical insufficiency / Delayed / 0.3-0.3
anemia / Delayed / 20.0
hypercholesterolemia / Delayed / 20.0
fluid retention / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
myopathy / Delayed / Incidence not known
sinus tachycardia / Rapid / Incidence not known
QT prolongation / Rapid / Incidence not known
pneumonitis / Delayed / Incidence not known
hypoglycemia / Early / Incidence not known

Mild

cough / Delayed / 6.5-17.0
dyspepsia / Early / 6.1-11.0
pharyngitis / Delayed / 0-11.0
rash / Early / 8.1-8.1
nocturia / Early / 0-6.2
vomiting / Early / 10.0
urticaria / Rapid / Incidence not known

Yonsa, ZYTIGA

Rx

Alpha-hydroxylase/C17,20-lyase (CYP17) inhibitor that blocks androgen biosynthesis
Used in combination with a corticosteroid for the treatment of metastatic high-risk castration-sensitive prostate cancer and metastatic castration-resistant prostate cancer
2 formulations (Zytiga and Yonsa) have different dosing recommendations and different food effects; do not substitute one for the other

For the treatment of metastatic prostate cancer. For the treatment of metastatic high risk hormone-sensitive prostate cancer, in combination with prednisone and androgen-deprivation therapy. Oral dosage (i.e., Zytiga and generic equivalents) Adult males

1,000 mg PO once daily in combination with prednisone 5 mg PO once daily and androgen deprivation therapy (ADT) (e.g., concurrent gonadotropin-releasing hormone (GnRH) analog or bilateral orchiectomy), until disease progression or unacceptable toxicity. Do not substitute Yonsa for or with Zytiga. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. First-line treatment with abiraterone and prednisone in combination with ADT significantly improved survival in patients with metastatic, hormone-sensitive prostate cancer compared with ADT alone in two clinical trials. In addition, a meta-analysis, indicated that adding abiraterone plus prednisone to ADT is an effective first-line treatment option for men with metastatic hormone-sensitive prostate cancer, offering an alternative to docetaxel.

For the treatment of metastatic castration-resistant prostate cancer, in combination with prednisone. Oral dosage (i.e., Zytiga and generic equivalents) Adult males

1,000 mg PO once daily in combination with prednisone 5 mg PO twice daily and androgen deprivation therapy (ADT) (e.g., concurrent gonadotropin-releasing hormone (GnRH) analog or bilateral orchiectomy), until disease progression or unacceptable toxicity. Do not substitute Yonsa for or with Zytiga. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter clinical trial, patients with metastatic castration resistant prostate cancer (CRPC) who had previously been treated with docetaxel were randomized to receive either abiraterone plus prednisone (n = 797) had significantly improved median overall survival (OS) compared with placebo plus prednisone (n = 398) (15.8 vs. 11.2 months). In a separate multicenter clinical trial, patients with metastatic CRPC who had not previously received cytotoxic chemotherapy who were treated with abiraterone plus prednisone (n = 546) also experienced significantly improved median OS compared with placebo plus prednisone (n = 542) (34.7 vs. 30.3 months), despite 44% of patients in the placebo arm receiving subsequent treatment with abiraterone. Additionally, patients treated with abiraterone had a significantly longer median time to initiation of cytotoxic chemotherapy (25.2 vs. 16.8 months) and median time to pain requiring the use of opioids (not reached vs. 23.7 months) compared with placebo.

For the treatment of metastatic castration-resistant prostate cancer, in combination with methylprednisolone. Oral dosage (Yonsa) Adult males

500 mg PO once daily in combination with methylprednisolone 4 mg PO twice daily and androgen deprivation therapy (ADT) (e.g., concurrent gonadotropin-releasing hormone (GnRH) analog or bilateral orchiectomy), until disease progression or unacceptable toxicity. Do not substitute Yonsa for or with Zytiga. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In one randomized clinical trial, treatment with abiraterone plus a corticosteroid significantly improved overall survival compared with placebo plus a corticosteroid in a multicenter, randomized, phase 3 clinical trial (15.8 months vs. 11.2 months). In a second randomized, phase 3 clinical trial of patients with metastatic CRPC who had not received prior cytotoxic chemotherapy, treatment with abiraterone plus corticosteroid also significantly improved overall survival compared with placebo plus corticosteroid (34.7 months vs. 30.3 months); radiographic progression-free survival was also significantly improved (not reached vs. 8.28 months) at a prespecified analysis. The median time to initiation of cytotoxic chemotherapy (25.2 months vs. 16.8 months) and the median time to opiate use for prostate cancer pain (not reached vs. 23.7 months) were also significantly better in the abiraterone arm.

Hepatic Impairment

Baseline Hepatic Impairment
Mild impairment (Child-Pugh class A): No dose adjustment recommended.
Moderate impairment (Child-Pugh class B): Reduce the starting dose of abiraterone (Zytiga) to 250 mg PO once daily. Reduce the starting dose of abiraterone (Yonsa) to 125 mg PO once daily. Monitor closely for treatment-related adverse reactions. If elevations in ALT/AST greater than 5 times upper limit of normal (ULN) or total bilirubin greater than 3 times ULN occur in patients with baseline moderate hepatic impairment, permanently discontinue abiraterone.
Severe impairment (Child-Pugh class C): Do not use abiraterone.
 
Treatment-Related Hepatotoxicity
Normal hepatic function or mild hepatic impairment at baseline, with treatment-related ALT/AST greater than 5 times ULN or total bilirubin greater than 3 times ULN: For patients with baseline normal hepatic function or mild hepatic impairment, hold abiraterone therapy. When LFTs either return to baseline, or AST/ALT are less than or equal to 2.5 times ULN and total bilirubin less than or equal to 1.5 times ULN, restart therapy at a reduced dose (Zytiga: 750 mg or 500 mg; Yonsa: 375 mg or 250 mg); monitor LFTs at least every 2 weeks for 3 months, and monthly thereafter. Discontinue treatment with abiraterone if hepatotoxicity recurs at a Zytiga dose of 500 mg once daily or a Yonsa dose of 250 mg once daily.
Moderate hepatic impairment at baseline, with treatment-related ALT/AST greater than 5 times ULN or total bilirubin greater than 3 times ULN: Permanently discontinue abiraterone therapy.
Concurrent elevation of ALT greater than 3 times ULN and total bilirubin greater than 2 times ULN without biliary obstruction or other causes: Permanently discontinue abiraterone therapy.

Renal Impairment

No dosage adjustment is recommended.

Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with abiraterone may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of abiraterone could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If abiraterone is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Abiraterone is a moderate inhibitor of CYP2D6.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Abiraterone inhbits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. If dextromethorphan- related side effects occur, a dose reduction or discontinuation of dextromethorphan may be necessary. In an in vivo drug-drug interaction trial, the Cmax and AUC of the CYP2D6 substrate dextromethorphan were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily along with prednisone 5 mg twice daily. The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Abiraterone inhbits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. If dextromethorphan- related side effects occur, a dose reduction or discontinuation of dextromethorphan may be necessary. In an in vivo drug-drug interaction trial, the Cmax and AUC of the CYP2D6 substrate dextromethorphan were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily along with prednisone 5 mg twice daily. The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Abiraterone inhbits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. If dextromethorphan- related side effects occur, a dose reduction or discontinuation of dextromethorphan may be necessary. In an in vivo drug-drug interaction trial, the Cmax and AUC of the CYP2D6 substrate dextromethorphan were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily along with prednisone 5 mg twice daily. The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with abiraterone may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of abiraterone could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If abiraterone is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Abiraterone is a moderate inhibitor of CYP2D6.
Acetaminophen; Dextromethorphan: (Moderate) Abiraterone inhbits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. If dextromethorphan- related side effects occur, a dose reduction or discontinuation of dextromethorphan may be necessary. In an in vivo drug-drug interaction trial, the Cmax and AUC of the CYP2D6 substrate dextromethorphan were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily along with prednisone 5 mg twice daily. The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Abiraterone inhbits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. If dextromethorphan- related side effects occur, a dose reduction or discontinuation of dextromethorphan may be necessary. In an in vivo drug-drug interaction trial, the Cmax and AUC of the CYP2D6 substrate dextromethorphan were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily along with prednisone 5 mg twice daily. The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Abiraterone inhbits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. If dextromethorphan- related side effects occur, a dose reduction or discontinuation of dextromethorphan may be necessary. In an in vivo drug-drug interaction trial, the Cmax and AUC of the CYP2D6 substrate dextromethorphan were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily along with prednisone 5 mg twice daily. The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Abiraterone inhbits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. If dextromethorphan- related side effects occur, a dose reduction or discontinuation of dextromethorphan may be necessary. In an in vivo drug-drug interaction trial, the Cmax and AUC of the CYP2D6 substrate dextromethorphan were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily along with prednisone 5 mg twice daily. The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Abiraterone inhbits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. If dextromethorphan- related side effects occur, a dose reduction or discontinuation of dextromethorphan may be necessary. In an in vivo drug-drug interaction trial, the Cmax and AUC of the CYP2D6 substrate dextromethorphan were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily along with prednisone 5 mg twice daily. The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Abiraterone inhbits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. If dextromethorphan- related side effects occur, a dose reduction or discontinuation of dextromethorphan may be necessary. In an in vivo drug-drug interaction trial, the Cmax and AUC of the CYP2D6 substrate dextromethorphan were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily along with prednisone 5 mg twice daily. The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.
Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with abiraterone may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of abiraterone could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If abiraterone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Abiraterone is a moderate inhibitor of CYP2D6.
Alogliptin; Pioglitazone: (Moderate) Closely monitor blood glucose if coadministration of pioglitazone with abiraterone is necessary. Pioglitazone is a CYP2C8 substrate and abiraterone is a weak CYP2C8 inhibitor. Concomitant use in a drug interaction trial increased pioglitazone exposure by 46%. Severe hypoglycemia has been reported when abiraterone was administered to patients receiving pioglitazone.
Amitriptyline: (Moderate) Monitor for an increase in amitriptyline-related adverse reactions if coadministration with abiraterone is necessary; a dose reduction of amitriptyline may be necessary. Amitriptyline is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor. Patients who are stable on a given dose of amitriptyline may become abruptly toxic when given abiraterone is concomitant therapy.
Amoxapine: (Moderate) Monitor for an increase in amoxapine-related adverse reactions if coadministration with abiraterone is necessary; a dose reduction of amoxapine may be necessary. Amoxapine is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor. Patients who are stable on a given dose of amoxapine may become abruptly toxic when given abiraterone is concomitant therapy.
Apalutamide: (Major) Avoid coadministration of abiraterone with apalutamide due to decreased abiraterone exposure. If concomitant use is unavoidable, increase the frequency of abiraterone administration to twice daily; reduce the frequency to once daily when apalutamide is discontinued. Abiraterone is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased abiraterone exposure by 55%.
Aripiprazole: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of abiraterone. Patients receiving both a CYP3A inhibitor plus abiraterone may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP2D6 and CYP3A substrate; abiraterone is a moderate CYP2D6 inhibitor.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with abiraterone may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of abiraterone could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If abiraterone is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Abiraterone is a moderate inhibitor of CYP2D6.
Brexpiprazole: (Moderate) Because brexpiprazole is partially metabolized by CYP2D6, patients should be carefully monitored for brexpiprazole-related adverse reactions during concurrent use of a moderate CYP2D6 inhibitor such as abiraterone. If abiraterone is used in combination with brexpiprazole and a moderate or strong CYP3A4 inhibitor, the brexpiprazole dose should be reduced to one-quarter (25%) of the usual dose and the patient should be carefully monitored for brexpiprazole-related adverse reactions. Brexpiprazole is primarily metabolized by CYP3A4 and CYP2D6. Abiraterone is a moderate inhibitor of CYP2D6. There are no dosing recommendations for brexpiprazole during use of a moderate CYP2D6 inhibitor alone.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Abiraterone inhbits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. If dextromethorphan- related side effects occur, a dose reduction or discontinuation of dextromethorphan may be necessary. In an in vivo drug-drug interaction trial, the Cmax and AUC of the CYP2D6 substrate dextromethorphan were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily along with prednisone 5 mg twice daily. The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Abiraterone inhbits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. If dextromethorphan- related side effects occur, a dose reduction or discontinuation of dextromethorphan may be necessary. In an in vivo drug-drug interaction trial, the Cmax and AUC of the CYP2D6 substrate dextromethorphan were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily along with prednisone 5 mg twice daily. The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with abiraterone may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of abiraterone could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If abiraterone is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Abiraterone is a moderate inhibitor of CYP2D6.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of codeine with abiraterone may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of abiraterone could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If abiraterone is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Abiraterone is a moderate inhibitor of CYP2D6.
Carbamazepine: (Major) Avoid coadministration of abiraterone with carbamazepine if possible due to decreased plasma concentrations of abiraterone. If concomitant use is unavoidable, increase the dosing frequency of abiraterone to twice daily. Reduce the dose back to the previous dose and frequency if carbamazepine is discontinued. Abiraterone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased abiraterone exposure by 55%.
Celecoxib; Tramadol: (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with abiraterone is necessary; also monitor for tramadol-related adverse reactions, including seizures and serotonin syndrome. Consider increasing the dose of tramadol if clinically appropriate. If abiraterone is discontinued, consider a dose reduction of tramadol and frequently monitor for signs or respiratory depression and sedation. Tramadol is metabolized by CYP2D6 to its active metabolite, M1; M1 is critical to the activity of tramadol. Abiraterone is a moderate CYP2D6 inhibitor. Concomitant use with CYP2D6 inhibitors may result in an increase in tramadol plasma levels and a decrease in the levels of the active metabolite, M1. In patients who have developed physical dependence to tramadol, decreased M1 levels may result in opioid withdrawal or reduced efficacy while increased tramadol levels may cause serotonin syndrome or seizures.
Chlordiazepoxide; Amitriptyline: (Moderate) Monitor for an increase in amitriptyline-related adverse reactions if coadministration with abiraterone is necessary; a dose reduction of amitriptyline may be necessary. Amitriptyline is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor. Patients who are stable on a given dose of amitriptyline may become abruptly toxic when given abiraterone is concomitant therapy.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with abiraterone may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of abiraterone could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If abiraterone is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Abiraterone is a moderate inhibitor of CYP2D6.
Chlorpheniramine; Dextromethorphan: (Moderate) Abiraterone inhbits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. If dextromethorphan- related side effects occur, a dose reduction or discontinuation of dextromethorphan may be necessary. In an in vivo drug-drug interaction trial, the Cmax and AUC of the CYP2D6 substrate dextromethorphan were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily along with prednisone 5 mg twice daily. The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Abiraterone inhbits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. If dextromethorphan- related side effects occur, a dose reduction or discontinuation of dextromethorphan may be necessary. In an in vivo drug-drug interaction trial, the Cmax and AUC of the CYP2D6 substrate dextromethorphan were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily along with prednisone 5 mg twice daily. The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Abiraterone inhbits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. If dextromethorphan- related side effects occur, a dose reduction or discontinuation of dextromethorphan may be necessary. In an in vivo drug-drug interaction trial, the Cmax and AUC of the CYP2D6 substrate dextromethorphan were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily along with prednisone 5 mg twice daily. The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with abiraterone may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of abiraterone could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If abiraterone is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Abiraterone is a moderate inhibitor of CYP2D6.
Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with abiraterone may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of abiraterone could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If abiraterone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Abiraterone is a moderate inhibitor of CYP2D6.
Clomipramine: (Moderate) Monitor for an increase in clomipramine-related adverse reactions if coadministration with abiraterone is necessary; a dose reduction of clomipramine may be necessary. Clomipramine is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor. Patients who are stable on a given dose of clomipramine may become abruptly toxic when given abiraterone is concomitant therapy.
Clozapine: (Moderate) Monitor for an increase in clozapine-related adverse reactions if coadministration with abiraterone is necessary; consider reducing the dose of clozapine if clinically appropriate. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Elevated plasma concentrations of clozapine occurring through CYP inhibition may potentially increase the risk of life-threatening arrhythmias, sedation, anticholinergic effects, seizures, orthostasis, or other adverse effects. If abiraterone is discontinued after dose adjustments are made, monitor for lack of clozapine effectiveness and consider increasing the clozapine dose if necessary. Clozapine is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor.
Codeine: (Moderate) Concomitant use of codeine with abiraterone may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of abiraterone could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If abiraterone is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Abiraterone is a moderate inhibitor of CYP2D6.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with abiraterone may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of abiraterone could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If abiraterone is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Abiraterone is a moderate inhibitor of CYP2D6.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with abiraterone may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of abiraterone could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If abiraterone is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Abiraterone is a moderate inhibitor of CYP2D6.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with abiraterone may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of abiraterone could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If abiraterone is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Abiraterone is a moderate inhibitor of CYP2D6.
Codeine; Promethazine: (Moderate) Concomitant use of codeine with abiraterone may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of abiraterone could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If abiraterone is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Abiraterone is a moderate inhibitor of CYP2D6.
Desipramine: (Moderate) Monitor for an increase in desipramine-related adverse reactions if coadministration with abiraterone is necessary; a dose reduction of desipramine may be necessary. Desipramine is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor. Patients who are stable on a given dose of desipramine may become abruptly toxic when given abiraterone is concomitant therapy.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Abiraterone inhbits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. If dextromethorphan- related side effects occur, a dose reduction or discontinuation of dextromethorphan may be necessary. In an in vivo drug-drug interaction trial, the Cmax and AUC of the CYP2D6 substrate dextromethorphan were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily along with prednisone 5 mg twice daily. The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.
Dextromethorphan: (Moderate) Abiraterone inhbits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. If dextromethorphan- related side effects occur, a dose reduction or discontinuation of dextromethorphan may be necessary. In an in vivo drug-drug interaction trial, the Cmax and AUC of the CYP2D6 substrate dextromethorphan were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily along with prednisone 5 mg twice daily. The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.
Dextromethorphan; Bupropion: (Moderate) Abiraterone inhbits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. If dextromethorphan- related side effects occur, a dose reduction or discontinuation of dextromethorphan may be necessary. In an in vivo drug-drug interaction trial, the Cmax and AUC of the CYP2D6 substrate dextromethorphan were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily along with prednisone 5 mg twice daily. The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Abiraterone inhbits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. If dextromethorphan- related side effects occur, a dose reduction or discontinuation of dextromethorphan may be necessary. In an in vivo drug-drug interaction trial, the Cmax and AUC of the CYP2D6 substrate dextromethorphan were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily along with prednisone 5 mg twice daily. The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.
Dextromethorphan; Guaifenesin: (Moderate) Abiraterone inhbits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. If dextromethorphan- related side effects occur, a dose reduction or discontinuation of dextromethorphan may be necessary. In an in vivo drug-drug interaction trial, the Cmax and AUC of the CYP2D6 substrate dextromethorphan were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily along with prednisone 5 mg twice daily. The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Abiraterone inhbits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. If dextromethorphan- related side effects occur, a dose reduction or discontinuation of dextromethorphan may be necessary. In an in vivo drug-drug interaction trial, the Cmax and AUC of the CYP2D6 substrate dextromethorphan were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily along with prednisone 5 mg twice daily. The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.
Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Moderate) Abiraterone inhbits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. If dextromethorphan- related side effects occur, a dose reduction or discontinuation of dextromethorphan may be necessary. In an in vivo drug-drug interaction trial, the Cmax and AUC of the CYP2D6 substrate dextromethorphan were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily along with prednisone 5 mg twice daily. The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Abiraterone inhbits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. If dextromethorphan- related side effects occur, a dose reduction or discontinuation of dextromethorphan may be necessary. In an in vivo drug-drug interaction trial, the Cmax and AUC of the CYP2D6 substrate dextromethorphan were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily along with prednisone 5 mg twice daily. The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.
Dextromethorphan; Quinidine: (Moderate) Abiraterone inhbits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. If dextromethorphan- related side effects occur, a dose reduction or discontinuation of dextromethorphan may be necessary. In an in vivo drug-drug interaction trial, the Cmax and AUC of the CYP2D6 substrate dextromethorphan were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily along with prednisone 5 mg twice daily. The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.
Doxepin: (Moderate) Monitor for an increase in doxepin-related adverse reactions if coadministration with abiraterone is necessary; a dose reduction of doxepin may be necessary. Doxepin is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor. Patients who are stable on a given dose of doxepin may become abruptly toxic when given abiraterone is concomitant therapy.
Doxorubicin Liposomal: (Major) Avoid coadministration of doxorubicin with abiraterone due to increased plasma concentrations of doxorubicin. Doxorubicin is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor. Clinically significant interactions have been reported with inhibitors of CYP2D6, resulting in increased concentration and clinical effect of doxorubicin.
Doxorubicin: (Major) Avoid coadministration of doxorubicin with abiraterone due to increased plasma concentrations of doxorubicin. Doxorubicin is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor. Clinically significant interactions have been reported with inhibitors of CYP2D6, resulting in increased concentration and clinical effect of doxorubicin.
Dutasteride; Tamsulosin: (Moderate) Monitor for an increase in tamsulosin-related adverse reactions if coadministration with abiraterone is necessary. Tamsulosin is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor. The effects of coadministration with a moderate CYP2D6 on the pharmacokinetics of tamsulosin have not been evaluated; however, the manufacturer of tamsulosin recommends caution with use.
Elbasvir; Grazoprevir: (Moderate) Administering abiraterone with elbasvir; grazoprevir may result in elevated abiraterone plasma concentrations. Abiraterone is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Eliglustat: (Major) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of abiraterone and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily; however, coadministration of eliglustat with both abiraterone and a strong or moderate CYP3A inhibitor is contraindicated. Abiraterone is a moderate CYP2D6 inhibitor; eliglustat is a CYP2D6 and CYP3A substrate. Coadministration with CYP2D6 inhibitors, such as abiraterone, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). Physiology-based pharmacokinetic (PBPK) models suggest that another moderate CYP2D6 inhibitor may increase the Cmax and AUC of eliglustat 3.8- and 4.5-fold, respectively, in EMs and 1.6-fold (both Cmax and AUC) in IMs. In addition, PBPK modeling suggests concomitant use of eliglustat (84 mg PO twice daily) with a moderate 2D6 inhibitor and a moderate 3A4 inhibitor may increase the Cmax and AUC of eliglustat 10.2- and 13.6-fold, respectively, in EMs and 4.2- and 5-fold, respectively, in IMs.
Enzalutamide: (Major) Avoid coadministration of abiraterone with enzalutamide due to decreased abiraterone exposure. If concomitant use is unavoidable, increase the frequency of abiraterone administration to twice daily; reduce the frequency to once daily when enzalutamide is discontinued. Abiraterone is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased abiraterone exposure by 55%.
Flecainide: (Moderate) Monitor for an increase in flecainide-related adverse reactions, including QT prolongation, if coadministration with abiraterone is necessary. Flecainide is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor. Plasma concentrations of flecainide may increase, especially in extensive CYP2D6 metabolizers.
Fluvoxamine: (Moderate) Monitor for an increase in fluvoxamine-related adverse reactions if coadministration with abiraterone is necessary. Fluvoxamine is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor. While none of the drugs studied for interactions significantly affected the pharmacokinetics of fluvoxamine, an in vivo study in CYP2D6 poor metabolizers (PM) demonstrated altered pharmacokinetic properties compared to extensive metabolizers (EM), with the Cmax, AUC, and half-life of fluvoxamine increased by 52%, 200%, and 62%, respectively. The manufacturer recommends caution in patients receiving concomitant drugs known to inhibit CYP2D6.
Fosphenytoin: (Major) Avoid the concomitant use of abiraterone and fosphenytoin. If fosphenytoin must be coadministered with abiraterone, increase the abiraterone dosing frequency to twice daily (i.e., 1,000 mg once daily to 1,000 mg twice daily). Reduce the dose back to the previous dose and frequency when fosphenytoin is discontinued. Abiraterone is a substrate of CYP3A4; fosphenytoin is a strong inducer of CYP3A4. Concomitant use may result in decreased concentrations of abiraterone resulting in reduced efficacy. In a drug interaction study, administration of abiraterone with another strong CYP3A inducer decreased exposure of abiraterone by 55%.
Gefitinib: (Moderate) Monitor for an increase in gefitinib-related adverse reactions if coadministration with abiraterone is necessary; the risk is increased in CYP2D6 poor metabolizers. Based on in vitro data, gefitinib is metabolized to O-desmethyl gefitinib by CYP2D6 and abiraterone is a CYP2D6 inhibitor. In healthy CYP2D6 poor metabolizers, the concentration of O-desmethyl gefitinib was not measurable and mean exposure to gefitinib was 2-fold higher compared to extensive metabolizers. The impact of CYP2D6 inhibitors on gefitinib pharmacokinetics has not been evaluated; however, the manufacturer recommends precautions based on exposure in patients with poor CYP2D6 metabolism.
Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with abiraterone may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of abiraterone could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If abiraterone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Abiraterone is a moderate inhibitor of CYP2D6.
Haloperidol: (Moderate) Monitor for an increase in haloperidol-related adverse reactions if coadministration with abiraterone is necessary. Haloperidol is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor. In pharmacokinetic studies, mild to moderately increased haloperidol concentrations have been reported when haloperidol was given concomitantly with drugs characterized as inhibitors of CYP2D6.
Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with abiraterone may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of abiraterone could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If abiraterone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Abiraterone is a moderate inhibitor of CYP2D6.
Hydrocodone: (Moderate) Concomitant use of hydrocodone with abiraterone may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of abiraterone could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If abiraterone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Abiraterone is a moderate inhibitor of CYP2D6.
Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with abiraterone may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of abiraterone could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If abiraterone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Abiraterone is a moderate inhibitor of CYP2D6.
Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with abiraterone may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of abiraterone could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If abiraterone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Abiraterone is a moderate inhibitor of CYP2D6.
Imipramine: (Moderate) Monitor for an increase in imipramine-related adverse reactions if coadministration with abiraterone is necessary; a dose reduction of imipramine may be necessary. Imipramine is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor. Patients who are stable on a given dose of imipramine may become abruptly toxic when given abiraterone is concomitant therapy.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid the concomitant use of abiraterone and rifampin. If rifampin must be coadministered with abiraterone, increase the abiraterone dosing frequency to twice daily (i.e., 1,000 mg once daily to 1,000 mg twice daily). Reduce the dose back to the previous dose and frequency when rifampin is discontinued. Abiraterone is a substrate of CYP3A4; rifampin is a strong inducer of CYP3A4. Concomitant use may result in decreased concentrations of abiraterone resulting in reduced efficacy. In a drug interaction study, administration of abiraterone with rifampin decreased exposure of abiraterone by 55%.
Isoniazid, INH; Rifampin: (Major) Avoid the concomitant use of abiraterone and rifampin. If rifampin must be coadministered with abiraterone, increase the abiraterone dosing frequency to twice daily (i.e., 1,000 mg once daily to 1,000 mg twice daily). Reduce the dose back to the previous dose and frequency when rifampin is discontinued. Abiraterone is a substrate of CYP3A4; rifampin is a strong inducer of CYP3A4. Concomitant use may result in decreased concentrations of abiraterone resulting in reduced efficacy. In a drug interaction study, administration of abiraterone with rifampin decreased exposure of abiraterone by 55%.
Lesinurad: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of abiraterone; monitor for potential reduction in efficacy. Abiraterone is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Lesinurad; Allopurinol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of abiraterone; monitor for potential reduction in efficacy. Abiraterone is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of abiraterone with lumacaftor; ivacaftor if possible due to decreased plasma concentrations of abiraterone. If concomitant use is unavoidable, increase the dosing frequency of abiraterone to twice daily. Reduce the dose back to the previous dose and frequency if lumacaftor; ivacaftor is discontinued. Abiraterone is a CYP3A4 substrate and lumacaftor is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased abiraterone exposure by 55%.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of abiraterone with lumacaftor; ivacaftor if possible due to decreased plasma concentrations of abiraterone. If concomitant use is unavoidable, increase the dosing frequency of abiraterone to twice daily. Reduce the dose back to the previous dose and frequency if lumacaftor; ivacaftor is discontinued. Abiraterone is a CYP3A4 substrate and lumacaftor is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased abiraterone exposure by 55%.
Maprotiline: (Moderate) Monitor for an increase in maprotiline-related adverse reactions if coadministration with abiraterone is necessary. Maprotiline is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor.
Metformin; Repaglinide: (Moderate) Monitor blood sugar more frequently if coadministration of repaglinide with abiraterone is necessary. Repaglinide is a CYP2C8 substrate and abiraterone is a weak CYP2C8 inhibitor. Severe hypoglycemia has been reported when abiraterone was administered to patients receiving repaglinide.
Metformin; Rosiglitazone: (Moderate) Monitor blood sugar more frequently if coadministration of rosiglitazone with abiraterone is necessary. Rosiglitazone is a CYP2C8 substrate and abiraterone is a weak CYP2C8 inhibitor. Severe hypoglycemia has been reported when abiraterone was administered to patients receiving thiazolidinediones.
Methadone: (Moderate) Consider a reduced dose of methadone with frequent monitoring for respiratory depression and sedation if concurrent use of abiraterone is necessary. If abiraterone is discontinued, consider increasing the methadone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Methadone is a CYP2D6 substrate, and coadministration with CYP2D6 inhibitors like abiraterone can increase methadone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of methadone. If abiraterone is discontinued, methadone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to methadone.
Metoprolol: (Moderate) Monitor for increased metoprolol adverse reactions including bradycardia and hypotension during coadministration. A dosage reduction for metoprolol may be needed based on response. Concurrent use may increase metoprolol exposure. Metoprolol is a CYP2D6 substrate; abiraterone is a moderate CYP2D6 inhibitor. In the presence of another moderate CYP2D6 inhibitor, the AUC of metoprolol was increased by 3.29-fold with no effect on the cardiovascular response to metoprolol.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for increased metoprolol adverse reactions including bradycardia and hypotension during coadministration. A dosage reduction for metoprolol may be needed based on response. Concurrent use may increase metoprolol exposure. Metoprolol is a CYP2D6 substrate; abiraterone is a moderate CYP2D6 inhibitor. In the presence of another moderate CYP2D6 inhibitor, the AUC of metoprolol was increased by 3.29-fold with no effect on the cardiovascular response to metoprolol.
Mitotane: (Major) Avoid the concomitant use of mitotane with abiraterone due to potential for decreased exposure to abiraterone. If coadministration cannot be avoided, increase the frequency of abiraterone administration to twice daily; resume previous abiraterone dosing after mitotane is discontinued. Mitotane is a strong CYP3A4 inducer and abiraterone is a CYP3A4 substrate. In a pharmacokinetic study involving healthy subjects, another strong CYP3A inducer decreased the mean AUC of abiraterone by 55%.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with abiraterone is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP2C8 substrate and abiraterone is a weak CYP2C8 inhibitor.
Nebivolol: (Major) Avoid the concomitant use of nebivolol and abiraterone. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as abiraterone, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible. If these drugs are coadministered, patients should be monitored for increased toxicity as well as increased therapeutic effect.
Nebivolol; Valsartan: (Major) Avoid the concomitant use of nebivolol and abiraterone. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as abiraterone, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible. If these drugs are coadministered, patients should be monitored for increased toxicity as well as increased therapeutic effect.
Nortriptyline: (Moderate) Monitor for an increase in nortriptyline-related adverse reactions if coadministration with abiraterone is necessary; a dose reduction of nortriptyline may be necessary. Nortriptyline is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor. Patients who are stable on a given dose of nortriptyline may become abruptly toxic when given abiraterone is concomitant therapy.
Oliceridine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and abiraterone is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and abiraterone may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If abiraterone is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Concomitant use of abiraterone with rifabutin may result in decreased serum concentrations of abiraterone. Abiraterone is a substrate of hepatic isoenzyme CYP3A4; rifabutin is a moderate inducer of this enzyme. Caution and close monitoring for decreased efficacy are advised if these drugs are used together.
Paroxetine: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with abiraterone is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor.
Perphenazine: (Moderate) Closely monitor for an increase in perphenazine-related adverse reactions if coadministration with abiraterone is necessary; reduce the dose of perphenazine if clinically appropriate. Perphenazine is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor. Concomitant administration may acutely increase plasma concentrations of perphenazine.
Perphenazine; Amitriptyline: (Moderate) Closely monitor for an increase in perphenazine-related adverse reactions if coadministration with abiraterone is necessary; reduce the dose of perphenazine if clinically appropriate. Perphenazine is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor. Concomitant administration may acutely increase plasma concentrations of perphenazine. (Moderate) Monitor for an increase in amitriptyline-related adverse reactions if coadministration with abiraterone is necessary; a dose reduction of amitriptyline may be necessary. Amitriptyline is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor. Patients who are stable on a given dose of amitriptyline may become abruptly toxic when given abiraterone is concomitant therapy.
Phenobarbital: (Major) Avoid coadministration of abiraterone with phenobarbital if possible due to decreased plasma concentrations of abiraterone. If concomitant use is unavoidable, increase the dosing frequency of abiraterone to twice daily. Reduce the dose back to the previous dose and frequency if phenobarbital is discontinued. Abiraterone is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased abiraterone exposure by 55%.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid coadministration of abiraterone with phenobarbital if possible due to decreased plasma concentrations of abiraterone. If concomitant use is unavoidable, increase the dosing frequency of abiraterone to twice daily. Reduce the dose back to the previous dose and frequency if phenobarbital is discontinued. Abiraterone is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased abiraterone exposure by 55%.
Phenytoin: (Major) Avoid coadministration of abiraterone with phenytoin if possible due to decreased plasma concentrations of abiraterone. If concomitant use is unavoidable, increase the dosing frequency of abiraterone to twice daily. Reduce the dose back to the previous dose and frequency if phenytoin is discontinued. Abiraterone is a CYP3A4 substrate and phenytoin is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased abiraterone exposure by 55%.
Pimozide: (Moderate) Caution is advisable during concurrent use of pimozide and moderate CYP2D6 inhibitors such as abiraterone. Pimozide is metabolized primarily through CYP3A4, and to a lesser extent CYP1A2 and CYP2D6. While the manufacturer has provided no guidance regarding pimozide use with mild or moderate CYP2D6 inhibitors, concurrent use of the drug with more potent inhibitors of CYP2D6 is contraindicated. Elevated concentrations of pimozide can lead to QT prolongation, ventricular arrhythmias, and sudden death.
Pioglitazone: (Moderate) Closely monitor blood glucose if coadministration of pioglitazone with abiraterone is necessary. Pioglitazone is a CYP2C8 substrate and abiraterone is a weak CYP2C8 inhibitor. Concomitant use in a drug interaction trial increased pioglitazone exposure by 46%. Severe hypoglycemia has been reported when abiraterone was administered to patients receiving pioglitazone.
Pioglitazone; Glimepiride: (Moderate) Closely monitor blood glucose if coadministration of pioglitazone with abiraterone is necessary. Pioglitazone is a CYP2C8 substrate and abiraterone is a weak CYP2C8 inhibitor. Concomitant use in a drug interaction trial increased pioglitazone exposure by 46%. Severe hypoglycemia has been reported when abiraterone was administered to patients receiving pioglitazone.
Pioglitazone; Metformin: (Moderate) Closely monitor blood glucose if coadministration of pioglitazone with abiraterone is necessary. Pioglitazone is a CYP2C8 substrate and abiraterone is a weak CYP2C8 inhibitor. Concomitant use in a drug interaction trial increased pioglitazone exposure by

46%. Severe hypoglycemia has been reported when abiraterone was administered to patients receiving pioglitazone.
Pitavastatin: (Moderate) Use abiraterone and pitavastatin together cautiously. Monitor closely for symptoms of pitavastatin toxicity such as myopathy (muscle pain or weakness). Patients should be instructed to report any complaints of muscle pain, tenderness, or weakness to their health care professional immediately. Pitavastatin is marginally metabolized by CYP2C9 and to a lesser extent by CYP2C8; it is possible that abiraterone, a weak CYP2C8 inhibitor, could increase pitavasstatin concentrations.
Primidone: (Major) Avoid coadministration of abiraterone with primidone if possible due to decreased plasma concentrations of abiraterone. If concomitant use is unavoidable, increase the dosing frequency of abiraterone to twice daily. Reduce the dose back to the previous dose and frequency if primidone is discontinued. Abiraterone is a CYP3A4 substrate and primidone is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased abiraterone exposure by 55%.
Promethazine; Dextromethorphan: (Moderate) Abiraterone inhbits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. If dextromethorphan- related side effects occur, a dose reduction or discontinuation of dextromethorphan may be necessary. In an in vivo drug-drug interaction trial, the Cmax and AUC of the CYP2D6 substrate dextromethorphan were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily along with prednisone 5 mg twice daily. The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.
Propranolol: (Moderate) Monitor blood pressure and heart rate if coadministration of propranolol with abiraterone is necessary. Propranolol is a CYP2D6 substrate and abiraterone is a CYP2D6 inhibitor. Concomitant use may result in hypotension and bradycardia.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and heart rate if coadministration of propranolol with abiraterone is necessary. Propranolol is a CYP2D6 substrate and abiraterone is a CYP2D6 inhibitor. Concomitant use may result in hypotension and bradycardia.
Protriptyline: (Moderate) Monitor for an increase in protriptyline-related adverse reactions if coadministration with abiraterone is necessary; a dose reduction of protriptyline may be necessary. Protriptyline is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor. Patients who are stable on a given dose of protriptyline may become abruptly toxic when given abiraterone is concomitant therapy.
Quinine: (Moderate) Use abiraterone, a CYP2C8 inhibitor, and quinine, a CYP2C8 substrate, together cautiously, as levels of quinine may be increased. Monitor closely for signs of quinine toxicity such as visual impairment, hypoglycemia, and cardiac arrhythmias. Additionally, quinine may inhibit drugs metabolized by CYP3A4, such as abiraterone, causing increased abiraterone levels.
Radium-223 Dichloride: (Major) Radium RA 223 dichloride is not recommended for use in combination with abiraterone plus prednisone or prednisolone outside of clinical trials. The risk of fractures (28.6% vs. 11.4%) and death (38.5% vs. 35.5%) was increased with the use of Radium RA 223 dichloride compared with placebo, both in combination with abiraterone and prednisone/prednisolone, in a randomized phase 3 trial. The safety and efficacy of Radium RA 223 dichloride and agents other than gonadotropin-releasing hormone analogues have not been established.
Repaglinide: (Moderate) Monitor blood sugar more frequently if coadministration of repaglinide with abiraterone is necessary. Repaglinide is a CYP2C8 substrate and abiraterone is a weak CYP2C8 inhibitor. Severe hypoglycemia has been reported when abiraterone was administered to patients receiving repaglinide.
Rifabutin: (Moderate) Concomitant use of abiraterone with rifabutin may result in decreased serum concentrations of abiraterone. Abiraterone is a substrate of hepatic isoenzyme CYP3A4; rifabutin is a moderate inducer of this enzyme. Caution and close monitoring for decreased efficacy are advised if these drugs are used together.
Rifampin: (Major) Avoid the concomitant use of abiraterone and rifampin. If rifampin must be coadministered with abiraterone, increase the abiraterone dosing frequency to twice daily (i.e., 1,000 mg once daily to 1,000 mg twice daily). Reduce the dose back to the previous dose and frequency when rifampin is discontinued. Abiraterone is a substrate of CYP3A4; rifampin is a strong inducer of CYP3A4. Concomitant use may result in decreased concentrations of abiraterone resulting in reduced efficacy. In a drug interaction study, administration of abiraterone with rifampin decreased exposure of abiraterone by 55%.
Rifapentine: (Major) Avoid the concomitant use of abiraterone and rifapentine due to the risk of decreased abiraterone efficacy. If concomitant use is unavoidable, increase the abiraterone dosing frequency to twice daily. Resume the previous dose and frequency when rifapentine is discontinued. Abiraterone is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased abiraterone exposure by 55%.
Rosiglitazone: (Moderate) Monitor blood sugar more frequently if coadministration of rosiglitazone with abiraterone is necessary. Rosiglitazone is a CYP2C8 substrate and abiraterone is a weak CYP2C8 inhibitor. Severe hypoglycemia has been reported when abiraterone was administered to patients receiving thiazolidinediones.
Spironolactone: (Major) Avoid using spironolactone in persons with prostate cancer receiving abiraterone. Spironolactone has been observed to increase prostate-specific antigen (PSA) concentrations and has been associated with tumor progression in persons with prostate cancer treated with abiraterone. Spironolactone is considered an androgen receptor antagonist but may exhibit androgen agonism in the setting of abiraterone-related androgen depletion.
Spironolactone; Hydrochlorothiazide, HCTZ: (Major) Avoid using spironolactone in persons with prostate cancer receiving abiraterone. Spironolactone has been observed to increase prostate-specific antigen (PSA) concentrations and has been associated with tumor progression in persons with prostate cancer treated with abiraterone. Spironolactone is considered an androgen receptor antagonist but may exhibit androgen agonism in the setting of abiraterone-related androgen depletion.
St. John's Wort, Hypericum perforatum: (Major) Avoid coadministration of abiraterone with St. John's Wort if possible due to decreased plasma concentrations of abiraterone. If concomitant use is unavoidable, increase the dosing frequency of abiraterone to twice daily. Reduce the dose back to the previous dose and frequency if St. John's Wort is discontinued. Abiraterone is a CYP3A4 substrate and St. John's Wort is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased abiraterone exposure by 55%.
Tamsulosin: (Moderate) Monitor for an increase in tamsulosin-related adverse reactions if coadministration with abiraterone is necessary. Tamsulosin is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor. The effects of coadministration with a moderate CYP2D6 on the pharmacokinetics of tamsulosin have not been evaluated; however, the manufacturer of tamsulosin recommends caution with use.
Thioridazine: (Contraindicated) Concomitant use of thioridazine and abiraterone is contraindicated due to the risk of QT prolongation and torsade de pointes (TdP) from elevated plasma concentrations of thioridazine. Thioridazine is a CYP2D6 substrate; abiraterone is an inhibitor of this enzyme.
Tramadol: (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with abiraterone is necessary; also monitor for tramadol-related adverse reactions, including seizures and serotonin syndrome. Consider increasing the dose of tramadol if clinically appropriate. If abiraterone is discontinued, consider a dose reduction of tramadol and frequently monitor for signs or respiratory depression and sedation. Tramadol is metabolized by CYP2D6 to its active metabolite, M1; M1 is critical to the activity of tramadol. Abiraterone is a moderate CYP2D6 inhibitor. Concomitant use with CYP2D6 inhibitors may result in an increase in tramadol plasma levels and a decrease in the levels of the active metabolite, M1. In patients who have developed physical dependence to tramadol, decreased M1 levels may result in opioid withdrawal or reduced efficacy while increased tramadol levels may cause serotonin syndrome or seizures.
Tramadol; Acetaminophen: (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with abiraterone is necessary; also monitor for tramadol-related adverse reactions, including seizures and serotonin syndrome. Consider increasing the dose of tramadol if clinically appropriate. If abiraterone is discontinued, consider a dose reduction of tramadol and frequently monitor for signs or respiratory depression and sedation. Tramadol is metabolized by CYP2D6 to its active metabolite, M1; M1 is critical to the activity of tramadol. Abiraterone is a moderate CYP2D6 inhibitor. Concomitant use with CYP2D6 inhibitors may result in an increase in tramadol plasma levels and a decrease in the levels of the active metabolite, M1. In patients who have developed physical dependence to tramadol, decreased M1 levels may result in opioid withdrawal or reduced efficacy while increased tramadol levels may cause serotonin syndrome or seizures.
Trimipramine: (Moderate) Monitor for an increase in trimipramine-related adverse reactions if coadministration with abiraterone is necessary; a dose reduction of trimipramine may be necessary. Trimipramine is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor. Patients who are stable on a given dose of trimipramine may become abruptly toxic when given abiraterone is concomitant therapy.

Abiraterone/Abiraterone acetate/Yonsa/ZYTIGA Oral Tab: 125mg, 250mg, 500mg

Adults

Zytiga: 1,000 mg PO once daily.
Yonsa: 500 mg PO once daily.

Geriatric

Zytiga: 1,000 mg PO once daily.
Yonsa: 500 mg PO once daily.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Infants

Not indicated.

Neonates

Not indicated.

Abiraterone acetate is converted to abiraterone, an androgen biosynthesis inhibitor. Abiraterone inhibits 17 alpha-hydroxylase/C17,20-lyase (CYP17), which decreases testosterone concentrations by catalyzing the conversion of pregnenolone and progesterone to their 17alpha-hydroxy derivatives, and the subsequent formation of dehydroepiandrosterone (DHEA) and androstenedione, respectively, by C17, 20 lyase activity; DHEA and androstenedione are androgens and are precursors of testosterone. In addition to reduced testosterone concentrations, inhibition of CYP17 by abiraterone can result in increased mineralocorticoid production by the adrenals. Concurrent corticosteroid (e.g., prednisone) administration suppresses adrenocorticotropic hormone (ACTH), helping to reduce the incidence and severity of adverse reactions related to mineralocorticoid excess.
 
Androgen sensitive prostate cancer responds to treatment that decreases androgen concentrations. Androgen deprivation therapies such as treatment with GnRH agonists or orchiectomy decrease androgen production in the testes but do not affect androgen production by the adrenals or in the tumor. In contrast, CYP17, inhibited by abiraterone, is expressed in testicular, adrenal, and prostate tumor tissues. It is not necessary to monitor the effect of abiraterone on serum testosterone concentrations. Changes in serum prostate specific antigen (PSA) concentrations may be observed but have not been shown to correlate with clinical benefit in individual patients.

Abiraterone acetate is administered orally, after which it is hydrolyzed to its active metabolite, abiraterone. Abiraterone is greater than 99% bound to albumin and alpha-1 acid glycoprotein. The apparent steady-state volume of distribution (Vd) is 19,669 +/- 13,358 L. After oral administration of 14C-abiraterone acetate, approximately 88% of the radioactive dose was recovered in feces (unchanged abiraterone acetate, 55%; abiraterone, 22%) and approximately 5% in urine.
 
There are 2 formulations of abiraterone acetate, one of which is a fine particle formulation (Yonsa). The fine particle formulation has an increased in vivo rate of dissolution, which improves the low bioavailability and food effects associated with the lipophilic, poorly water-soluble standard formulation. In a multicenter, randomized, open-label trial (n = 53) designed to evaluate the therapeutic equivalence, steady-state pharmacokinetics, and safety of Yonsa 500 mg with Zytiga 1,000 mg, average absolute testosterone levels of 0.1 ng/dL or less were achieved in 25% of patients with metastatic castration-resistant prostate cancer treated with Yonsa compared to 17% of those receiving Zytiga. Both agents led to similar PSA-50 response rates, and abiraterone trough concentrations were similar between treatments. No new safety concerns were observed.
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP2D6, CYP3A4/5, CYP2C8, SULT2A1, P-glycoprotein (P-gp), OATP1B1
Following oral administration, radiolabeled abiraterone acetate is hydrolyzed to abiraterone (active metabolite) likely via unidentified esterase activity; the conversion is not mediated by cytochrome P450. The 2 main circulating metabolites of abiraterone in human plasma (abiraterone sulphate and N-oxide abiraterone sulphate) are inactive and account for about 43% each of exposure. Metabolism to N-oxide abiraterone sulphate occurs via CYP3A4 and SULTA2A1; metabolism to abiraterone sulphate occurs via SULTA2A1. Although concomitant strong CYP3A4 inducers should be avoided when possible during abiraterone treatment, strong CYP3A4 inhibitors did not have a clinically meaningful effect on the pharmacokinetics of abiraterone. Additionally, abiraterone inhibits CYP2D6 (moderate) and CYP2C8 (weak). In vitro studies show that at clinically relevant concentrations, abiraterone acetate is an inhibitor of P-gp. In vitro, abiraterone also has the potential to inhibit CYP1A2, CYP2D6, CYP2C8, OATP1B1, and to a lesser extent CYP2C9, CYP2C19, and CYP3A4/5. Abiraterone and its major metabolites inhibit the hepatic uptake transporter OATP1B1 in vitro; however, there are no clinical data to confirm a transporter-based interaction.

Oral Route

After oral administration to patients with metastatic CRPC, the median time to maximum plasma abiraterone concentrations (Tmax) was 2 hours. The AUC of Zytiga was approximately 2-fold higher at steady-state compared to a single 1,000-mg dose. At the recommended daily dose of 1,000 mg, the mean steady-state Cmax of Zytiga was 226 +/- 178 ng/mL and the AUC was 993 +/- 639 ng x hour/mL. Zytiga concentrations were dose proportional over a range of 250 mg to 1,000 mg; however, the mean AUC was only increased by 8% when the dose was doubled from 1,000 mg to 2,000 mg. After a single dose of Yonsa 500 mg in overnight fasted healthy volunteers, the geometric mean Cmax was 73 +/- 44 ng/mL and the AUC was 373 +/- 249 ng x hour/mL. Single dose Yonsa concentrations were dose proportional over a range of 125 mg to 625 mg.
 
Food impacts the pharmacokinetics of different formulations of abiraterone (i.e., Zytiga and Yonsa) in different ways, which affects whether or not a particular dosage form may be taken with food. When administered as a single dose with a high-fat meal (56% to 60% fat, 900 to 1,000 calories), the Cmax of Yonsa was approximately 6.5-fold higher and the AUC was 4.4-fold higher compared to overnight fasting in healthy volunteers.Yonsa may be administered with or without food.
 
Food should not be consumed for at least 2 hours before or 1 hour after Zytiga is administered. In healthy subjects, administration of a single dose with a low-fat meal (7% fat, 300 calories) increased the Cmax and AUC of Zytiga by approximately 7-fold and 5-fold, respectively, compared with overnight fasting; administration with a high-fat meal (57% fat, 825 calories) increased the Cmax and AUC by approximately 17-fold and 10-fold, respectively. When given 1 hour before or 2 hours after a medium fat meal (25% fat, 491 calories), the AUC of Zytiga increased by 1.6-fold and 7-fold, respectively. In patients with metastatic CRPC, the Zytiga steady-state AUC was similar when taken with low-fat meals compared to administration 1 hour before or 2 hours after a meal; steady-state AUC increased by approximately 2-fold when taken with high-fat meals. Given normal variation in meal content and composition, taking Zytiga with meals may result in highly variable exposures.

Pregnancy

Pregnancy should be avoided by female partners of men receiving therapy with abiraterone during treatment and for 3 weeks after the last dose. Instruct pregnant women or females of reproductive potential to NOT handle abiraterone tablets without protection (e.g., gloves). Although there are no adequately controlled studies in pregnant women, abiraterone can cause fetal harm or death when administered during pregnancy based on its mechanism of action and animal studies. If the partner of a patient is exposed to abiraterone during pregnancy, apprise her of the potential hazard to the fetus. When administered to rats during organogenesis in an embryo-fetal developmental toxicity study, embryo-fetal lethality (increased post-implantation loss, resorptions, decreased live fetuses), fetal developmental delay (skeletal effects), and urogenital effects (bilateral ureter dilation) occurred at systemic exposures of approximately 0.03 times the AUC in patients. Decreased fetal anogenital distance occurred at systemic exposures of approximately 0.1 times the AUC in patients, and decreased fetal body weight occurred at approximately 0.3 times the AUC in patients.[44156] [63206]

The safety and efficacy of abiraterone have not been established in females. It is not known whether abiraterone is present in human milk, although many drugs are excreted in human milk. Due to the potential for serious adverse reactions in nursing infants from abiraterone, women should avoid breast-feeding if receiving abiraterone.