- Tablets, oral 250 mg
Inhibits CYP17, an enzyme required for androgen biosynthesis, which is expressed in testicular, adrenal, and prostatic tumor tissues.
T max is 2 h. C max is approximately 226 ng/mL. C max and AUC were approximately 17- and 10-fold higher, respectively, when administered with a high-fat meal.
More than 99% is protein bound to albumin and alpha-1 acid glycoprotein. Vd is approximately 19,669 L.
Abiraterone acetate is hydrolyzed to the active metabolite abiraterone; it is further metabolized to the inactive metabolites abiraterone sulphate and N-oxide abiraterone sulphate via CYP3A4 and SULT2A1.
Eliminated in the feces (approximately 88%) and the urine (approximately 5%); elimination half-life is approximately 12 h.
Special PopulationsRenal Function Impairment
Systemic exposure did not increase in subjects with ESRD on dialysis compared with subjects with normal renal function. No dosage adjustment is necessary.Hepatic Function Impairment
Systemic exposure increased approximately 1.1- and 3.6-fold in subjects with mild and moderate hepatic impairment, respectively. The mean half-life of was prolonged to approximately 18 h in subjects with mild hepatic impairment and to approximately 19 h in subjects with moderate hepatic impairment. No dosage adjustment is necessary in patients with mild hepatic impairment; however, a reduced dose is recommended in patients with moderate hepatic impairment. Avoid use in patients with severe hepatic impairment (Child-Pugh class C).
Indications and Usage
In combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer who have received prior chemotherapy containing docetaxel.
Women who are or may become pregnant.
Dosage and AdministrationAdults
PO 1,000 mg once daily in combination with prednisone 5 mg twice daily.Dosage adjustment
Hepatotoxicity during treatment
For ALT and/or AST elevations more than 5 times the ULN or total bilirubin elevation of more than 3 times the ULN, withhold treatment until LFTs return to baseline or ALT and AST are 2.5 times or less than the ULN and total bilirubin is 1.5 times or less than the ULN; then reinitiate at 750 mg once daily. If hepatotoxicity recurs on 750 mg/day, withhold treatment until LFTs return to baseline or ALT and AST are 2.5 times or less than the ULN and total bilirubin is 1.5 times or less than the ULN; then reinitiate at 500 mg once daily. If hepatotoxicity recurs on 500 mg/day, discontinue treatment.Hepatic function impairment
250 mg once daily in patients with moderate hepatic impairment (Child-Pugh class B). Permanently discontinue treatment if elevations in ALT and/or AST of more than 5 times the ULN or total bilirubin of more than 3 times the ULN occur. Avoid use in patients with severe hepatic impairment (Child-Pugh class C).
- Administer on an empty stomach, at least 2 h before and 1 h after food.
- Swallow tablets whole with water.
- Women who are pregnant or women who may be pregnant should not handle abiraterone without protection (eg, gloves).
Store between 59° and 86°F.
Drug InteractionsCYP2D6 substrates (eg, dextromethorphan, thioridazine)
Plasma concentrations of CYP2D6 substrates may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Avoid coadministration with CYP2D6 substrates that have a narrow therapeutic index (eg, thioridazine). If concurrent use cannot be avoided, administer with caution and consider a dose reduction of the CYP2D6 substrate.CYP3A4 strong inducers (eg, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine)
Based on in vitro data, abiraterone is a CYP3A4 substrate. The effects of strong CYP3A4 inducers on the pharmacokinetics of abiraterone have not been evaluated in vivo. Avoid coadministration or use with caution.CYP3A4 strong inhibitors (eg, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole)
Based on in vitro data, abiraterone is a CYP3A4 substrate. The effects of strong CYP3A4 inhibitors on the pharmacokinetics of abiraterone have not been evaluated in vivo. Avoid coadministration or use with caution.
Hot flush (19%); hypertension (9%); arrhythmia (eg, atrial fibrillation, atrial flutter, atrial tachycardia, AV block complete, bradyarrhythmia, bradycardia, conduction disorder, supraventricular tachycardia, tachycardia, ventricular tachycardia) (7%); chest pain or discomfort (eg, angina pectoris, chest pain, angina unstable) (4%); cardiac failure (eg, cardiac failure congestive, left ventricular dysfunction, cardiogenic shock, cardiomegaly, cardiomyopathy, ejection fraction decreased) (2%).
Diarrhea (18%); dyspepsia (6%).
UTI (12%); urinary frequency (7%); nocturia (6%).
High triglycerides (63%); high AST (31%); low potassium (28%); low phosphorus (24%); high ALT (11%); high total bilirubin (7%).
Edema (eg, edema peripheral, pitting edema, generalized edema) (27%).
Joint swelling or discomfort (eg, arthritis, arthralgia, joint swelling, joint stiffness) (30%); muscle discomfort (eg, muscle spasms, musculoskeletal pain, myalgia, musculoskeletal discomfort, musculoskeletal stiffness) (26%).
Cough (11%); upper respiratory tract infection (5%).
Monitor for symptoms and signs of adrenocortical insufficiency, particularly if patients are withdrawn from prednisone, have prednisone dose reductions, or experience unusual stress. Monitor patients for hypertension, hypokalemia, and fluid retention at least once per month. Measure ALT, AST, and bilirubin levels prior to starting treatment, every 2 weeks for the first 3 months of treatment, and then monthly thereafter. In patients with moderate hepatic impairment receiving a reduced abiraterone dose, measure ALT, AST, and bilirubin prior to the start of treatment, every week for the first month, every 2 weeks for the following 2 months of treatment, and monthly thereafter. For patients who resume treatment after an interruption for hepatotoxicity, monitor serum transaminases and bilirubin at a minimum of every 2 weeks for 3 months, and monthly thereafter.
Category X . Contraindicated in women who are or may become pregnant.
Undetermined. Not indicated for use in women.
Not indicated for use in children.
Dosage reduction is recommended in patients with moderate hepatic impairment. Avoid use in patients with severe hepatic impairment.
Reported in patients receiving abiraterone in combination with prednisone, following interruption of daily steroids and/or with concurrent infection or stress.
Marked increases in liver enzymes, leading to drug discontinuation or dosage modification, have occurred.
May cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels. Use with caution in patients with a history of CV disease.
No overdosage has been reported.
- Inform patients that abiraterone and prednisone are used together, and that they should not interrupt or stop either of these medications without consulting their health care provider.
- Inform patients receiving GnRH agonists that they need to maintain this treatment during the course of treatment with abiraterone and prednisone.
- Inform patients that abiraterone must not be taken with food and that no food should be consumed for at least 2 h before and for at least 1 h after they take their dose of abiraterone. Inform patients that the tablets should be swallowed whole with water.
- Inform patients that taking abiraterone with food causes increased exposure and this may result in adverse reactions.
- Inform patients in the event of a missed daily dose of abiraterone or prednisone, they should take their normal dose the following day. If more than 1 daily dose is skipped, patients should be told to inform their health care provider.
- Inform patients of the common side effects, such as joint swelling or discomfort, muscle discomfort, diarrhea, peripheral edema, hypokalemia, hypertension, and UTI.
- Inform patients that liver function will be monitored using blood tests.
- Inform patients that abiraterone may harm a developing fetus; thus, women who are pregnant or who may be pregnant should not handle abiraterone without protection (eg, gloves).
- Advise male patients to use a condom if having sex with a pregnant woman. The patient should use a condom and another effective method of birth control if he is having sex with a woman of child bearing potential. These measures are required during and for 1 wk after treatment with abiraterone.
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