Abiraterone acetate is converted in vivo to abiraterone, an androgen biosynthesis inhibitor, which inhibits 17α hydroxylase and C17,20-lyase involved in androgen biosynthesis and mineralocorticoid production. A phase III trial in castration-resistant prostate cancer patients, who were previously treated with docetaxel, showed a survival benefit for patients treated with abiraterone + prednisone compared to those receiving placebo + prednisone.
Pharmacokinetics are dose-proportional in the therapeutic range. Administration with food increases exposure 10-fold. Time to maximum plasma concentration is 2 hours (fasting state). Accumulation is observed at steady state.
Extensive distribution to peripheral tissues. PPB: 99.8%.
Abiraterone acetate is rapidly hydrolyzed to abiraterone by esterases, then undergoes sulphation, hydroxylation and oxidation, mainly in the liver by CYP3A4 and SULT2A1, to inactive metabolites.
|Half-life||12 ± 5 hours (terminal)|
|Feces||88% of dose, 55% unchanged|
- In combination with prednisone for the treatment of metastatic, castration-resistant prostate cancer (mCRPC) in patients who:
- are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy
- have received prior chemotherapy containing docetaxel after failure of androgen deprivation therapy
- In combination with prednisone and androgen deprivation therapy (ADT) for the treatment of patients with newly diagnosed hormone-sensitive high-risk metastatic prostate cancer who may have received up to 3 months of prior ADT
Extravasation Potential: Not applicable
The following table contains side effects observed more frequently with abiraterone+prednisone compared to prednisone alone, in asymptomatic or mildly symptomatic patients with CRPC plus other potentially severe/life-threatening adverse events reported from other trials/sources.
|ORGAN SITE||SIDE EFFECT* (%)||ONSET**|
|Nausea, vomiting (13%)||E|
|Lymphopenia (7%) (severe)||E|
|Hepatobiliary||↑ LFTs (41%) (6% severe)||E|
|Metabolic / Endocrine||Abnormal electrolyte(s) (26%) (severe 5%, ↓ PO4, ↑ Na or ↑ Ca)||E|
|Adrenal insufficiency (<2%)||E|
|↑ Cholesterol (55%) (severe <1%) (in docetaxel pre-treated patients)||E|
|↓ K (17%) , mineralocorticoid effects||E|
|↑ Triglycerides (22%)||E|
|Musculoskeletal||Fracture (6%)||D L|
|Musculoskeletal pain (32%)||E|
|Rhabdomyolysis (also myopathy; rare)||E|
|Nervous System||Depression (3%) (newly diagnosed patients)||E|
|Renal||Creatinine increased (<2%)||E|
|Reproductive and breast disorders||Androgen deprivation symptoms (22%)||E|
|Respiratory||Cough, dyspnea (17%)||E|
|Pneumonitis (allergic alveolitis; rare)||E|
|Urinary||Urinary symptoms (10%)||E|
* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal reports.
Dose-limiting side effects are underlined.
** I = immediate (onset in hours to days) E = early (days to weeks)
D = delayed (weeks to months) L = late (months to years)
The most common side effects for abiraterone include ↑ triglycerides and cholesterol, ↑ LFTs, fatigue, musculoskeletal pain, abnormal electrolyte(s), edema, constipation and androgen deprivation symptoms (e.g. hot flashes).
Severe hepatotoxicity, including acute liver failure and fulminant hepatitis (with fatal outcomes) has been reported in ± 7% of patients and is more common in patients with abnormal LFTs at baseline. Most cases of hepatotoxicity appear to be reversible after discontinuation of abiraterone. Clinical trials excluded patients with active hepatitis, significantly abnormal LFTs and in some trials, patients with liver metastases.
Cases of myopathy and rhabdomyolysis occurred generally within the first month of treatment and resolved following drug discontinuation.
Mineralocorticoid effects, which include hypertension, fluid retention and hypokalemia, are commonly reported. Patients on prednisone may require an increased dose of a corticosteroid before, during and after stressful conditions, such as surgery, trauma or severe infections.
There were slightly more cardiac events (mainly grades 1 or 2) reported in the abiraterone group (11-16%) than in the placebo group (7-14%).
Refer to protocol by which patient is being treated. Patients should continue to receive the GnRH agonist during abiraterone treatment unless they have had prior orchiectomy. Control hypertension and correct hypokalemia before treatment.
Abiraterone – Metastatic castration-resistant prostate cancer (mCRPC)
Oral: 1000 mg on an empty stomach once daily, plus
Prednisone 10 mg PO once daily
(Note: Prednisone 5 mg PO bid has been used in one of the phase III trials)
Abiraterone – Newly diagnosed high-risk metastatic prostate cancer
Oral: 1000 mg on an empty stomach once daily, plus
Prednisone 5 mg PO once daily
Grade 3 ALT/AST
Grade 3 total bilirubin
Hold; monitor liver function closely until recovery to baseline THEN
Reduce to 500mg/day
Grade 4 ↑ LFTs
ALT/AST > 3 x ULN AND total bilirubin > 2 x ULN (in the absence of biliary obstruction or other causes)
OR ≥ Grade 3 ↑ LFTs after dose modification
OR confirmed pneumonitis/allergic alveolitis
|Discontinue permanently||Not applicable||Not applicable|
|Hypokalemia persists despite optimal K supplements and adequate oral intake
Other mineralcorticoid effects persist
|No change||If on 5mg/day, may increase to 10 mg/day|
Refer to the table above for dose modifications with hepatotoxicity during treatment.
|Hepatic Impairment (at baseline)||Dose|
|Mild (Child-Pugh Class A)||No change|
|Moderate (Child-Pugh Class B)||Do not use abiraterone|
|Severe (Child-Pugh Class C)||Do not use abiraterone|
No adjustment required
No overall differences in effectiveness or adverse effects were seen between elderly and younger patients.
Not indicated and has not been studied in children.
- Abiraterone must be taken on an empty stomach. No solid or liquid food should be eaten for at least 2 hours before and at least 1 hour after the dose.
- The tablets should be swallowed whole with a glass of water.
- If an abiraterone dose is missed, skip this and take the next dose as scheduled. Do not double the dose to make up for the missed one.
- Since abiraterone may harm the fetus, women who are pregnant or who may become pregnant should handle abiraterone with protection (e.g. gloves).
- Women who are or may potentially be pregnant (not for use in women)
- Patients who have a hypersensitivity to this drug or any of its components
- Moderate-severe hepatic impairment at baseline
- Severe (grade 4) hepatotoxicity
- Use with caution in patients with cardiovascular disease as they were not included in clinical trials. Increased mineralocorticoid levels from CYP17 inhibition may cause hypertension, hypokalemia and fluid retention. Use with caution in patients whose underlying medical conditions may be affected by these effects.
- Use with caution in patients taking other medications associated with myopathy or rhabdomyolysis (e.g. statins)
- Adrenal insufficiency has been reported in patients taking abiraterone and prednisone. Increased corticosteroid dosage may be required before, during and after the stressful situation.
- Contains lactose and should not be used in patients with hereditary galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption.
- Efficacy may be lower in patients who have been treated previously with ketoconazole for their prostate cancer.
- The safety and efficacy of combination abiraterone and cytotoxic chemotherapy use has not been established.
Other Drug Properties:
Documented in animals
Carcinogenicity was demonstrated in male rats. No information available in humans.
Excretion into breast milk:
Adequate contraception should be used by both sexes during treatment, and for at least 1 week after the last dose. Barrier contraception (including condoms) should be used.
(may be reversible)
Abiraterone is mainly metabolized by CYP3A4 and SULT2A1. The drug moderately inhibits CYP2C9, 2C19 and P-gp in vitro (may not be clinically significant), and is a potent CYP1A2 inhibitor (no observed ↑ in systemic theophylline exposure), potent CYP2D6 and CYP2C8 inhibitor in vitro. Exercise caution with concomitant use of CYP2C8/1A2 substrates; monitor patient closely.
|CYP2D6 substrates (e.g. beta-blockers, tramadol, nortriptyline, mirtazapine, serotonin-H3 antagonists)||↑ substrate exposure and/or toxicity (up to 200% with dextromethorphan)||abiraterone is a potent CYP2D6 inhibitor||Caution; avoid co-administration with CYP 2D6 substrates with narrow therapeutic range. If no alternative option, consider ↓ dose of the concomitant 2D6 substrate.|
|CYP3A4 inducers (i.e. phenytoin, rifampin, dexamethasone, carbamazepine, phenobarbital, St. John’s Wort, etc)||↓ abiraterone concentration (rifampin ↓ AUC of single-dose abiraterone by 55%) and/or efficacy||↑ metabolism of abiraterone, a CYP3A4 substrate||Avoid strong CYP3A4 inducers; caution and monitor efficacy if must co-administer.|
|CYP3A4 inhibitors (i.e. ketoconazole, clarithromycin, ritonavir, fruit or juice from grapefruit, Seville oranges or starfruit)||↑ abiraterone exposure and/or toxicity (theoretical); no significant effect observed with single dose of abiraterone||↓ metabolism of abiraterone, a CYP3A4 substrate||Avoid or use caution with strong CYP3A4 inhibitors during treatment|
|Spironolactone||may stimulate disease progression||spironolactone may bind and activate the wild-type androgen receptor||Avoid use with abiraterone|
|P-glycoprotein substrates (i.e. verapamil, digoxin, morphine, ondansetron)||↑ substrate exposure and/or toxicity (theoretical)||Abiraterone is a P-gp inhibitor||Caution and monitor|
|OATP1B1 substrates (i.e. rosuvastatin)||↑ substrate exposure (no clinical data)||abiraterone inhibits OATP1B1||Caution and monitor|
|CYP 2C8 substrates (i.e. paclitaxel, sorafenib, amiodarone, pioglitazone, enzalutamide)||↑ substrate exposure (unlikely clinically significant with pioglitazone)||abiraterone inhibits CYP2C8||Caution and monitor CYP2C8 substrates with narrow therapeutic range|
|Drugs that increase risk of myopathy (e.g. statins)||↑ risk of myopathy/rhabdomyolysis||Additive||Caution and monitor for myopathy/rhabdomyolysis|
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
|Monitor Type||Monitor Frequency|
|Blood pressure, serum potassium||Baseline and monthly|
Liver function tests, bilirubin
|Baseline, every 2 weeks for the first 3 months and monthly thereafter, or as clinically indicated|
Monitor for adrenal insufficiency
|As clinically indicated when prednisone is withdrawn, or during periods of infection/stress|
Monitor for mineralocorticoid excess
|As clinically indicated if patient continues on abiraterone after stopping prednisone|
Cholesterol and triglycerides
|Baseline, every 2 to 3 months and as clinically indicated|
Clinical toxicity assessment for hypertension, edema, GI, musculoskeletal effects, hot flashes, urinary symptoms, cardiac and respiratory toxicity
|At each visit|
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
Exceptional Access Program (EAP Website)
- abiraterone - Metastatic castrate-resistant prostate cancer, with specific criteria ()
de Bono JS, Logothetis CJ, Molina A, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 2011;364:1995-2005.
Product Monograph: Abiraterone (Zytiga®). Janssen Inc., February 12, 2018.
Prescribing information: Zytiga® (abiraterone). Janssen Biotech Inc. (US), December 2012.
Ryan CJ, Smith MR, de Bono JS, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 2013;368(2):138-48.
July 2018 added new indication; updated dosing, dose modifications, precautions sections
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