ARX-Abiraterone

MIMS Revision Date: 01 December 2025

1 Name of Medicine

Abiraterone acetate.

2 Qualitative and Quantitative Composition

Each 250 mg tablet contains 250 mg of abiraterone acetate.
Each 500 mg tablet contains 500 mg abiraterone acetate.
Excipient(s) with known effect. Contains sugars as lactose.
The 250 mg tablets contain 198.65 mg of lactose monohydrate.
The 500 mg tablets contain 253.2 mg of lactose monohydrate.
For a full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

ARX-Abiraterone 250 mg tablets are white to off-white, oval shaped film coated tablets, debossed with "35" on one side and plain on the other side.
ARX-Abiraterone 500 mg film-coated tablets are pinkish brown colour, oval-shaped, biconvex film coated tablets, debossed with "46" on one side and plain on the other side.

4 Clinical Particulars

4.1 Therapeutic Indications

ARX-Abiraterone is indicated in combination with prednisolone for the treatment of:
newly diagnosed high-risk metastatic hormone sensitive prostate cancer (mHSPC) in combination with androgen deprivation therapy (ADT); or
patients with metastatic advanced prostate cancer (castration resistant prostate cancer, mCRPC) who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy (ADT); or
patients with mCRPC who have received prior chemotherapy containing a taxane.

4.2 Dose and Method of Administration

The recommended dosage of ARX-Abiraterone is 1 g (four 250 mg tablets or two 500 mg tablets) as a single daily dose that must not be taken with food. ARX-Abiraterone tablets must be taken as a single dose once daily on an empty stomach. ARX-Abiraterone must be taken at least two hours after eating and food must not be eaten for at least one hour after taking ARX-Abiraterone. The tablets must be swallowed whole with water (see Section 5.2 Pharmacokinetic Properties, Absorption).
Dosage of prednisolone. For hormone sensitive prostate cancer (mHSPC), ARX-Abiraterone is used with 5 mg prednisolone daily (see Section 4.4 Special Warnings and Precautions for Use, Corticosteroid withdrawal and coverage of stress situations).
For metastatic castration-resistant prostate cancer (mCRPC), ARX-Abiraterone is used with 10 mg prednisolone daily (see Section 4.4 Special Warnings and Precautions for Use, Corticosteroid withdrawal and coverage of stress situations).
Recommended monitoring. Serum transaminases and bilirubin should be measured prior to starting treatment with ARX-Abiraterone, every two weeks for the first three months of treatment and monthly thereafter. Blood pressure, serum potassium and fluid retention should be monitored monthly (see Section 4.4 Special Warnings and Precautions for Use).
Patients started on ARX-Abiraterone who were receiving a LHRH agonist should continue to receive a LHRH agonist.
Renal insufficiency. No dosage adjustment is necessary for patients with renal impairment.
Hepatic insufficiency. No dosage adjustment is necessary for patients with pre-existing mild hepatic impairment. There are no data on the clinical safety and efficacy of multiple doses of abiraterone acetate when administered to patients with moderate or severe hepatic impairment (Child-Pugh Class B or C). No dose adjustment can be predicted. ARX-Abiraterone should be used with caution in patients with moderate hepatic impairment, only if the benefit clearly outweighs the possible risk. ARX-Abiraterone should not be used in patients with pre-existing severe hepatic impairment (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use; Section 5.2 Pharmacokinetic Properties).
For patients who develop hepatotoxicity during treatment with ARX-Abiraterone (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) increases above 5 times the upper limit of normal or bilirubin increases above 3 times the upper limit of normal) treatment should be withheld immediately until liver function tests normalise (see Section 4.4 Special Warnings and Precautions for Use). Re-treatment following return of liver function tests to the patient's baseline may be given at a reduced dose of 500 mg (one 500 mg tablet or two 250 mg tablets) once daily. For patients being retreated, serum transaminases and bilirubin should be monitored at a minimum of every two weeks for three months and monthly thereafter. If hepatotoxicity recurs at the reduced dose of 500 mg daily, discontinue treatment with ARX-Abiraterone. Reduced doses should not be taken with food.
If patients develop severe hepatotoxicity (ALT or AST 20 times the upper limit of normal) anytime while on therapy, ARX-Abiraterone should be discontinued and patients should not be re-treated with ARX-Abiraterone.

4.3 Contraindications

ARX-Abiraterone is contraindicated in women who are or may potentially be pregnant.
ARX-Abiraterone is contraindicated in patients with severe hepatic impairment [Child Pugh Class C] (see Section 4.2 Dose and Method of Administration; Section 4.4 Special Warnings and Precautions for Use; Section 5.2 Pharmacokinetic Properties).
ARX-Abiraterone plus prednisolone is contraindicated in combination with Xofigo (radium 223 dichloride; see Section 4.4).

4.4 Special Warnings and Precautions for Use

Hypertension, hypokalaemia and fluid retention due to mineralocorticoid excess. ARX-Abiraterone should be used with caution in patients with a history of cardiovascular disease. The safety of abiraterone acetate in patients with left ventricular ejection fraction (LVEF) < 50% or New York Heart Association (NYHA) Class III or IV heart failure (in study 301) or NYHA Class II to IV heart failure (in studies 3011 and 302) was not established. Before treatment with ARX-Abiraterone, hypertension must be controlled, and hypokalaemia must be corrected.
Abiraterone may cause hypertension, hypokalaemia and fluid retention (see Section 4.8 Adverse Effects (Undesirable Effects)) as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition (see Section 5.1 Pharmacodynamic Properties). Co-administration of a corticosteroid suppresses adrenocorticotropic hormone (ACTH) drive, resulting in a reduction in the incidence and severity of these adverse reactions. Caution is required in treating patients whose underlying medical conditions might be compromised by increases in blood pressure, hypokalaemia or fluid retention, e.g. those with heart failure, recent myocardial infarction or ventricular arrhythmia. In postmarketing experience, QT prolongation and Torsades de Pointes have been observed in patients who develop hypokalaemia or have underlying cardiovascular conditions while taking abiraterone.
Blood pressure, serum potassium and fluid retention should be monitored at least monthly.
Hepatotoxicity. Marked increases in liver enzymes leading to drug discontinuation or dosage modification occurred in controlled clinical studies (see Section 4.8 Adverse Effects (Undesirable Effects)). Very rarely hepatitis fulminant and hepatic failure has been seen. Serum transaminase and bilirubin levels should be measured prior to starting treatment with abiraterone, every two weeks for the first three months of treatment, and monthly thereafter. If clinical symptoms or signs suggestive of hepatotoxicity develop, serum transaminases, should be measured immediately. If at any time the ALT or AST rises above 5 times the upper limit of normal or the bilirubin rises above 3 times the upper limit of normal, treatment with abiraterone should be interrupted immediately and liver function closely monitored.
Re-treatment with abiraterone may only take place after the return of liver function tests to the patient's baseline and at a reduced dose level (see Section 4.2 Dose and Method of Administration).
If patients develop severe hepatotoxicity (ALT or AST 20 times the upper limit of normal) anytime while on therapy, abiraterone should be discontinued and patients should not be re-treated with abiraterone.
Patients with active or symptomatic viral hepatitis were excluded from clinical trials; thus, there are no data to support the use of abiraterone acetate in this population.
There are no data on the clinical safety and efficacy of multiple doses of abiraterone acetate when administered to patients with moderate or severe hepatic impairment (Child-Pugh Class B or C). The use of ARX-Abiraterone should be cautiously assessed in patients with moderate hepatic impairment, in whom the benefit clearly should outweigh the possible risk. ARX-Abiraterone should not be used in patients with severe hepatic impairment (see Section 4.3 Contraindications; Section 4.2 Dose and Method of Administration; Section 5.2 Pharmacokinetic Properties).
Corticosteroid withdrawal and coverage of stress situations. Caution is advised and monitoring for adrenocortical insufficiency should occur if patients need to be withdrawn from prednisolone. If abiraterone is continued after corticosteroids are withdrawn, patients should be monitored for symptoms of mineralocorticoid excess.
In patients on prednisolone who are subjected to unusual stress, increased dosage of a corticosteroid may be indicated before, during and after the stressful situation. 17α hydroxylase inhibition by abiraterone decreases glucocorticoid production.
Hyperglycaemia. The use of glucocorticoids could increase hyperglycaemia, therefore blood sugar should be measured frequently in patients with diabetes.
Hypoglycaemia. Isolated cases of hypoglycaemia have been reported when abiraterone plus prednisone*/prednisolone was administered to patients with pre-existing diabetes receiving pioglitazone or repaglinide (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Blood glucose should be monitored in patients with diabetes.
Use with chemotherapy. The safety and efficacy of concomitant use of abiraterone with cytotoxic chemotherapy has not been established.
Use in combination with radium 223 dichloride. In a randomised clinical trial in patients with asymptomatic or mildly symptomatic bone-predominant metastatic castration resistant prostate cancer, at the time of unblinding, the addition of radium 223 dichloride to abiraterone plus *prednisone/prednisolone showed an increase in mortality and an increased rate of fracture. Radium 223 dichloride is not recommended for use in combination with ARX-Abiraterone plus prednisolone. It is recommended that subsequent treatment with radium 223 dichloride is not initiated for at least 5 days after the last administration of ARX-Abiraterone in combination with prednisolone.
Use in the elderly. No data available.
Paediatric use. This medicine is not for use in children.
Effects on laboratory tests. No data available.
* All safety data from studies co-administering abiraterone with prednisone alone or prednisone/prednisolone have been included in the PI to ensure completeness of safety information. This safety information is applicable to coadministration of ARX-Abiraterone with prednisolone.

4.5 Interactions with Other Medicines and Other Forms of Interactions

In vitro studies. In vitro studies with human hepatic microsomes showed that abiraterone is a strong inhibitor of CYP1A2, CYP2D6 and CYP2C8 and a moderate inhibitor of CYP2C9, CYP2C19 and CYP3A4/5. The major metabolites, abiraterone sulphate and N-oxide abiraterone sulphate are also strong inhibitors of CYP2C8 in vitro. In vitro abiraterone, abiraterone sulphate and N-oxide abiraterone sulphate are inhibitors of OATP1B1. The clinical relevance of this inhibition is not clear.
Clinical studies. CYP2D6. In a study to determine the effects of abiraterone acetate (plus prednisone) on a single dose of the CYP2D6 substrate dextromethorphan, the systemic exposure (AUC) of dextromethorphan was increased approximately 200%. The AUC₂₄ for dextrorphan, the active metabolite of dextromethorphan, increased approximately 33%.
Caution is advised when abiraterone is administered with drugs activated by or metabolised by CYP2D6, particularly with drugs that have a narrow therapeutic index. Dose reduction of narrow therapeutic index drugs metabolised by CYP2D6 should be considered the same.
CYP3A4. Abiraterone is a substrate of CYP3A4. In a clinical pharmacokinetic interaction study of 20 healthy subjects pre-treated with a strong CYP3A4 inducer (rifampicin, 600 mg daily for 6 days) followed by a single dose of abiraterone acetate 1000 mg, the mean plasma C_max and AUC_∞ of abiraterone were decreased by 55%.
Strong inducers of CYP3A4 (e.g. phenytoin, carbamazepine, rifampicin, rifabutin, rifapentine, phenobarbital) during treatment with ARX-Abiraterone is to be avoided, or used with careful evaluation of clinical efficacy, if there is no therapeutic alternative.
In a separate clinical pharmacokinetic interaction study of 19 healthy subjects, co-administration of ketoconazole, a strong inhibitor of CYP3A4 (ketoconazole 400 mg for 6 days), had no clinically meaningful effect on the pharmacokinetics of abiraterone.
CYP2C8. In a CYP2C8 drug-drug interaction trial in healthy subjects, the AUC of pioglitazone was increased by 46% and the AUCs for M-III and M-IV, the active metabolites of pioglitazone, each decreased by 10%, when pioglitazone was given together with a single dose of 1000 mg abiraterone acetate.
Patients should be monitored for signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic index if used concomitantly with ARX-Abiraterone. Examples of medicinal products metabolized by CYP2C8 include pioglitazone and repaglinide (see Section 4.4 Special Warnings and Precautions for Use, Hypoglycaemia).
CYP1A2. In a clinical study to determine the effects of abiraterone acetate (plus prednisone) on a single dose of the CYP1A2 substrate theophylline, no increase in systemic exposure of theophylline was observed.
Use with spironolactone. Spironolactone binds to the androgen receptor and may increase prostate specific antigen (PSA) levels. Use with ARX-Abiraterone is not recommended (see Section 5.1 Pharmacodynamic Properties, Pharmacodynamic effects).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility. In fertility studies in both male and female rats (4-and 3-weeks), abiraterone acetate reduced fertility, which was completely reversible in 4 to 16 weeks after abiraterone acetate was stopped.
In studies in mice (4 weeks), rats (4 up to 26-weeks) and monkeys (up to 39-weeks), decreases in testosterone levels, atrophy, aspermia/hypospermia, and/or hyperplasia in the reproductive system were observed at > 125 mg/kg/day in mice, ≥ 30 mg/kg/day in rats and ≥ 250 mg/kg/day in monkeys and were consistent with the antiandrogenic pharmacological activity of abiraterone. These effects were observed at exposure levels similar to or lower than the human clinical exposure, based on abiraterone AUC.
Use in pregnancy. (Category D)
ARX-Abiraterone is contraindicated in women who are or may potentially be pregnant (see Section 4.3 Contraindications).
There are no human data on the use of abiraterone in pregnancy and abiraterone is not for use in women of child-bearing potential. Maternal use of a CYP17 inhibitor is expected to produce changes in hormone levels that could affect development of the fetus.
In an embryofetal developmental study in the rat, abiraterone acetate at ≥ 10 mg/kg/day affected pregnancy including reduced fetal weight and survival, delayed ossification, and increases in late resorptions and post implantation loss with a subsequent reduction in live fetuses. Effects on the external genitalia (decreased fetal ano-genital distance) were observed though abiraterone acetate was not teratogenic.
In these fertility and developmental toxicity studies performed in the rat, all effects were related to the pharmacological activity of abiraterone.
It is not known if abiraterone or its metabolites are present in semen. A condom is required if the patient is engaged in sexual activity with a pregnant woman. If the patient is engaged in sex with a woman of child-bearing potential, a condom is required along with another effective contraceptive method.
To avoid inadvertent exposure, women who are pregnant or women who may be pregnant should not handle ARX-Abiraterone without protection, e.g. gloves.
Use in lactation. ARX-Abiraterone is not for use in women.
It is not known if either abiraterone or its metabolites are excreted in human breast milk.

4.7 Effects on Ability to Drive and Use Machines

No studies on the effects of abiraterone on the ability to drive or use machines have been performed. It is not anticipated that abiraterone will affect the ability to drive and use machines.

4.8 Adverse Effects (Undesirable Effects)

Adverse drug reactions from clinical trials. In an analysis of adverse reactions of composite Phase 3 studies with abiraterone, adverse reactions that were observed in ≥ 10% of patients were peripheral oedema, hypokalaemia, hypertension, urinary tract infection, and alanine aminotransferase increased, and/or aspartate aminotransferase increased.
Abiraterone may cause hypertension, hypokalaemia and fluid retention as a pharmacodynamic consequence of its mechanism of action. In Phase 3 studies anticipated mineralocorticoid effects were seen more commonly in patients treated with abiraterone versus patients treated with placebo; hypokalaemia 18% versus 8%, hypertension 22% versus 16% and fluid retention (peripheral oedema) 23% versus 17%, respectively. Grades 3/4 hypokalaemia were observed in 6% versus 1%, grades 3/4 hypertension were observed in 7% versus 5%, and grades 3/4 fluid retention oedema were observed in 1% versus 1% of patients treated with abiraterone versus patients treated with placebo, respectively. Mineralocorticoid effects generally were able to be successfully managed medically. Concomitant use of a corticosteroid reduces the incidence and severity of these adverse drug reactions (see Section 4.4 Special Warnings and Precautions for Use).
In a Phase 3 study of patients with newly diagnosed high-risk mHNPC or mHSPC (Study 3011) who were receiving and remained on ADT (a luteinising hormone-releasing hormone [LHRH] agonist or orchiectomy), and abiraterone acetate was administered at a dose of 1000 mg daily in combination with low dose prednisone (5 mg daily) and ADT in the active treatment arm; ADT and placebo were given to control patients. The median duration of treatment with abiraterone was 24 months.
Adverse reactions that occurred at a rate of ≥ 1% (all grades) are shown in Table 1.

In a Phase 3 study of patients with metastatic castration resistant prostate cancer who had received prior chemotherapy (study 301) who were using a LHRH agonist, or were previously treated with orchiectomy, abiraterone was administered at a dose of 1 g daily in combination with low dose *prednisone/prednisolone (10 mg daily) in the active treatment arm; placebo plus low dose prednisolone (10 mg daily) was given to control patients. Patients were intolerant to or had failed up to two prior chemotherapy regimens, one of which contained a taxane. The average duration of treatment with abiraterone was 8 months.
Adverse drug reactions that occurred at a rate of ≥ 1% (all grades) are shown in Table 2.
In a second placebo-controlled, multicentre Phase 3 clinical study (study 302), in asymptomatic or mildly symptomatic, chemotherapy naïve patients with metastatic advanced prostate cancer who were using a LHRH agonist or were previously treated with orchiectomy, abiraterone was also administered at a dose of 1 g daily in combination with low dose *prednisone/prednisolone 10 mg daily in the active treatment arm. Placebo plus low dose *prednisone/prednisolone 10 mg daily was given to control patients. The average duration of treatment with abiraterone in study 302 was 13.8 months.
Adverse drug reactions that occurred at a rate of ≥ 1% (all grades) are shown in Table 3.
The most common adverse drug reactions that resulted in drug discontinuation in combined data from phase 3 studies were alanine aminotransferase increased, aspartate aminotransferase increased, and hypokalaemia (each in < 1% of patients taking abiraterone).
The adverse drug reaction, adrenal insufficiency, occurred in the Phase 3 clinical studies at a rate 0.3% in patients taking abiraterone and at a rate of 0.1% inpatients taking placebo.
In the Phase 3 studies, 70% of patients were 65 years and over, and 27% were 75 years and over for patients taking abiraterone. Adverse effects were more common in patients ≥ 75 years old in both the abiraterone and placebo groups.
Cardiovascular effects. The Three Phase 3 studies excluded patients with uncontrolled hypertension, clinically significant heart disease as evidenced by myocardial infarction, arterial thrombotic events in the past 6 months, severe or unstable angina, or NYHA Class III or IV heart failure (study 301) or Class II to IV heart failure (studies 3011 and 302) or cardiac ejection fraction measurement of < 50%. All patients enrolled (both active and placebo-treated patients) were concomitantly treated with androgen deprivation therapy, predominately with the use of LHRH agonists, which has been associated with diabetes, myocardial infarction, cerebrovascular accident and sudden cardiac death. The incidence of cardiovascular adverse reactions in the Phase 3 studies in patients taking abiraterone versus patients taking placebo were as follows: atrial fibrillation 2.6% vs. 2.0%, tachycardia 1.9% vs. 1.0%, angina pectoris 1.7% vs. 0.8%, cardiac failure 0.7% vs. 0.2% and arrhythmia 0.7% vs. 0.5%.
Hepatotoxicity. Drug-associated hepatotoxicity with elevated ALT, AST and total bilirubin has been reported in patients treated with abiraterone. Across Phase 3 clinical studies, hepatotoxicity grades 3 and 4 (e.g. ALT or AST increases of > 5 X ULN or bilirubin increases > 1.5 X ULN) were reported in approximately 4% of patients who received abiraterone, typically during the first 3 months after starting treatment. In Study 3011, grade 3 or 4 hepatotoxicity was observed in 8.4% of patients treated with abiraterone acetate. Ten patients who received abiraterone acetate were discontinued because of hepatotoxicity; two had Grade 2 hepatotoxicity, six had Grade 3 hepatotoxicity, and two had Grade 4 hepatotoxicity. No patient died of hepatotoxicity in Study 3011. In the 301 clinical study, patients whose baseline ALT or AST were elevated were more likely to experience liver function test elevations than those beginning with normal values. When elevations of either ALT or AST > 5 X ULN, or elevations in bilirubin > 3 X ULN were observed, abiraterone was withheld or discontinued.
Hepatic metastases and baseline elevations in alkaline phosphatase associated with prostate cancer were present in a few of these patients. In two instances marked increases in liver function tests occurred (see Section 4.4 Special Warnings and Precautions for Use). These two patients with normal baseline hepatic function, experienced ALT or AST elevations 15 to 40 X ULN and bilirubin elevations 2 to 6 X ULN. Upon discontinuation of abiraterone, both patients had normalisation of their liver function tests and one patient was re-treated with abiraterone without recurrence of the elevations. In study 302, grade 3 or 4 ALT or AST elevations were observed in 35 (6.5%) patients treated with abiraterone. Aminotransferase elevations resolved in all but 3 patients (2 with new multiple liver metastases and 1 with AST elevation approximately 3 weeks after the last dose of abiraterone). In Phase 3 clinical studies, treatment discontinuations due to ALT and AST increases or abnormal hepatic function were reported in 1.1% of patients treated with abiraterone and 0.6% of patients treated with placebo. No deaths were reported due to hepatotoxicity events.
In clinical trials, the risk for hepatotoxicity was mitigated by exclusion of patients with baseline hepatitis or significant abnormalities of liver function tests. In the 3011 trial, patients with baseline ALT and AST > 2.5 X ULN, bilirubin > 1.5 X ULN or those with active or symptomatic viral hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction were excluded. In the 301 trial, patients with baseline ALT and AST ≥ 2.5X ULN in the absence of liver metastases and > 5 X ULN in the presence of liver metastases were excluded. In the 302 trial patients with liver metastases were not eligible and patients with baseline ALT and AST ≥ 2.5 X ULN were excluded. Abnormal liver function tests developing in patients participating in clinical trials were vigorously managed by requiring treatment interruption and permitting re-treatment only after return of liver function tests to the patient's baseline (see Section 4.2 Dose and Method of Administration). Patients with elevations of ALT or AST > 20X ULN were not re-treated. The safety of re-treatment in such patients is unknown. The mechanism for hepatotoxicity associated with abiraterone is not understood.
Post-marketing data. Adverse drug reactions identified during the post-marketing experience based on spontaneous reports with abiraterone acetate are described below. The frequencies are provided according to the following convention:
Very common ≥ 1/10; common ≥ 1/100 and < 1/10; uncommon ≥ 1/1,000 and < 1/100; rare ≥ 1/10,000 and < 1/1,000; very rare < 1/10,000; isolated reports: frequency unknown.
System organ class. Respiratory, thoracic and mediastinal disorders. Rare: Allergic alveolitis.
System organ class. Musculoskeletal and connective tissue disorders. Uncommon: Rhabdomyolysis, myopathy.
System organ class. Gastrointestinal disorders. Very common: Diarrhoea.
System organ class. Hepatobiliary disorders. Very rare: Hepatitis fulminant, hepatic failure.
System organ class. Cardiac disorders. Very rare: QT prolongation and Torsades de Pointes (observed in patients who developed hypokalaemia or had underlying cardiovascular conditions).
System organ class. Immune system disorders - hypersensitivity. Very rare: Anaphylactic reaction (severe allergic reactions that include, but are not limited to difficulty swallowing or breathing, swollen face, lips, tongue or throat, or an itchy rash (urticaria)).
Reporting suspected adverse effects. Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.
* All safety data from studies co-administering abiraterone with prednisone alone or prednisone/prednisolone have been included in the PI to ensure completeness of safety information. This safety information is applicable to coadministration of ARX-Abiraterone with prednisolone.

4.9 Overdose

There have been no reports of overdose of abiraterone acetate during clinical studies.
There is no specific antidote. In the event of an overdose, administration of abiraterone acetate should be stopped and general supportive measures undertaken, including monitoring for arrhythmias. Liver function also should be assessed.
Contact the Poisons Information Centre (telephone 131126) for advice on management of overdose.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action. Abiraterone acetate is converted in vivo to abiraterone, an androgen biosynthesis inhibitor. Specifically, abiraterone selectively inhibits the enzyme 17α hydroxylase/C17,20-lyase (CYP17). This enzyme is expressed in and is required for androgen biosynthesis in testicular, adrenal and in prostatic tumour tissues. It catalyses the conversion of pregnenolone and progesterone into testosterone precursors, DHEA and androstenedione, respectively, by 17α hydroxylation and cleavage of the C17,20 bond. CYP17 inhibition also results in increased mineralocorticoid production by the adrenals (see Section 4.4 Special Warnings and Precautions for Use).
Androgen-sensitive prostatic carcinoma responds to treatment that decreases androgen levels. Androgen deprivation therapies, such as treatment with luteinising hormone-releasing hormone (LHRH) agonists or orchiectomy, decrease androgen production in the testes but do not affect androgen production by the adrenals or in the tumour. Treatment with abiraterone decreases serum testosterone to undetectable levels (using commercial assays) when given with LHRH agonists (or orchiectomy).
Pharmacodynamic effects. Abiraterone decreases serum testosterone and other androgens to levels lower than those achieved by the use of LHRH agonists alone or by orchiectomy. Prostate specific antigen (PSA) serves as a biomarker in patients with prostate cancer. In a Phase 3 clinical study of patients who failed prior chemotherapy with taxanes, 29% of patients treated with abiraterone, versus 6% of patients treated with placebo, had at least a 50% decline from baseline in PSA levels.
Use of spironolactone. Patients in pivotal clinical trials with abiraterone acetate were not allowed to use spironolactone as spironolactone binds to the androgen receptor and may increase PSA levels.
Effects on the QT interval. In a cardiovascular safety study in patients with metastatic advanced prostate cancer there were no significant effects of abiraterone acetate on the cardiac QT/QTc interval.
Clinical trials. The efficacy of abiraterone was established in three randomised placebo controlled multicentre Phase 3 clinical studies (studies 3011, 301 and 302) of patients with hormone naïve metastatic prostate cancer and metastatic castration resistant prostate cancer.
Study 3011 enrolled patients who were newly diagnosed (within 3 months of randomisation) mHNPC who had high-risk prognostic factors. High-risk prognosis was defined as having at least 2 of the following 3 risk factors: (1) Gleason score of ≥ 8; (2) presence of 3 or more lesions on bone scan; (3) presence of measurable visceral (excluding lymph node disease) metastasis. In the active arm, abiraterone acetate was administered at a dose of 1 g daily in combination with low dose prednisone 5 mg once daily in addition to ADT (LHRH agonist or orchiectomy), which was the standard of care treatment. Patients in the control arm received ADT and placebos for abiraterone acetate.
Study 302 enrolled patients who were asymptomatic or mildly symptomatic and had not received prior chemotherapy, whereas study 301 enrolled patients who received prior chemotherapy containing a taxane. In both studies patients were using a LHRH agonist or were previously treated with orchiectomy. In the active treatment arms, abiraterone was administered at a dose of 1 g daily in combination with low dose *prednisone/prednisolone 5 mg twice daily. Control patients received placebo and low dose *prednisone/prednisolone 5 mg twice daily.
Because changes in PSA serum concentration do not always predict clinical benefit, in all studies patients were maintained on abiraterone until specific discontinuation criteria were met for each study below.
Study 3011 (patients with newly diagnosed high-risk metastatic hormone naïve prostate cancer (mHNPC) or hormone sensitive prostate cancer (mHSPC). In Study 3011, (n=1199) the median age of enrolled patients was 67 years. The ECOG performance status was 0 or 1 for 97% of patients. Patients with uncontrolled hypertension, significant heart disease, or NYHA Class II or worse heart failure were excluded. Co-primary efficacy endpoints were overall survival (OS) and radiographic progression-free survival (rPFS). The median baseline pain score, as measured by the Brief Pain Inventory Short Form (BPI-SF) was 2.0 in both the treatment and placebo groups. In addition to the co primary endpoint measures, benefit was also assessed using time to skeletal-related event (SRE), time to subsequent therapy for prostate cancer, time to initiation of chemotherapy, time to pain progression and time to PSA progression.
In the 3011 study, treatment continued until disease progression, withdrawal of consent, the occurrence of unacceptable toxicity, or death.
Radiographic progression-free survival was defined as the time from randomisation to the occurrence of radiographic progression or death from any cause. Radiographic progression included progression by bone scan (according to modified PCWG2) or progression of soft tissue lesions by CT or MRI (according to RECIST 1.1).
At the planned rPFS analysis there were 593 events; 239 (40.0%) of patients treated with abiraterone acetate and 354 (58.8%) of patients treated with placebo had radiographic evidence of progression or had died. A significant difference in rPFS between treatment groups was observed (see Table 4 and Figure 1).

At the planned first interim analysis (IA-1) for overall survival, four hundred and six (406; 47.7% of the total number of deaths required at the final analysis) deaths had occurred (169 subjects in the AA-P group and 237 subjects in the placebo group). A statistically significant improvement in OS in favour of AA-P plus ADT was observed with a 38% reduction in the risk of death (HR=0.621; 95% CI: 0.509, 0.756) compared to Placebo plus ADT. Median survival was not reached in the AA-P group versus 34.7 months in the Placebo group (p < 0.0001, crossing the pre-specified boundary for OS at Interim Analysis 1 of 0.010) (see Table 5 and Figure 2). The study was un-blinded based on the magnitude of clinical benefit observed and patients in the placebo group were offered treatment with abiraterone acetate. Survival continued to be followed after this IA.
Subgroup analyses consistently favour treatment with abiraterone acetate (see Figure 3).
In addition to the observed improvements in overall survival and rPFS, benefit was demonstrated for abiraterone acetate vs. placebo treatment in all prospectively-defined secondary endpoint measures as follows:
Time to skeletal-related event (SRE). There was a 30% reduction in the risk of skeletal-related events (HR = 0.703; 95% CI: [0.539, 0.916] p < 0.0086). The median time to SRE has not been reached for the abiraterone acetate or placebo study arm.
Time to PSA progression based on PCWG2 criteria. The median time to PSA progression was 33.2 months for patients receiving abiraterone acetate and 7.4 months for patients receiving placebo (HR = 0.299; 95% CI: [0.255, 0.352], p < 0.0001).
Time to subsequent therapy. The median time to subsequent therapy at the time of interim analysis was not reached for patients receiving abiraterone acetate and was 21.6 months for patients receiving placebo (HR = 0.415; 95% CI: [0.346, 0.497], p < 0.0001).
Time to initiation of chemotherapy. The median time to initiation of chemotherapy was not reached for patients receiving abiraterone acetate and was 38.9 months for patients receiving placebo (HR = 0.443; 95% CI: [0.349, 0.561], p < 0.0001).
Time to pain progression. The median time to pain progression was not reached for patients receiving abiraterone acetate and was 16.6 months for patients receiving placebo (HR = 0.695; 95% CI: [0.583, 0.829], p = < 0.0001).
The majority of exploratory endpoints favoured treatment with abiraterone acetate (AA-P) and prednisone over Placebo. A statistically significant improvement in prostate cancer-specific OS was observed for AA-P treatment compared with Placebo (HR=0.547, p < 0.0001). A confirmed PSA response was observed in 91.0% of subjects in the AA-P group and 66.8% of subjects in the Placebo group (relative risk=1.362; p < 0.0001). The overall response rate (complete plus partial response) in subjects with measurable disease at baseline was significantly higher in the AA-P group compared with those in the Placebo group (p=0.0002).
The time to degradation analyses of patient reported outcome (PRO) measures consistently demonstrated that treatment with AA-P delayed degradation and progression of pain, functional status, fatigue and health-related quality of life. Based on the change from baseline using repeated measures mixed-effect model statistically significant differences were observed between AA-P and Placebo as early as Cycle 2 and maintained throughout the study.
Study 302 (asymptomatic or mildly symptomatic patients who did not receive prior chemotherapy). In study 302, (n=1088) the median age of enrolled patients was 71 years for patients treated with abiraterone plus prednisone or prednisolone and 70 years for patients treated with placebo plus prednisone or prednisolone. The ECOG performance status was 0 for 76% of patients, and 1 for 24% of patients in both arms. Co-primary efficacy endpoints were overall survival and radiographic progression-free survival (rPFS). In addition to the co-primary endpoint measures, benefit was also assessed using time to opiate use for cancer pain, time to initiation of cytotoxic chemotherapy, time to deterioration in ECOG performance score by ≥ 1 point and time to PSA progression based on Prostate Cancer Working Group-2 (PCWG2) criteria.
In study 302, treatments were discontinued at the time of unequivocal clinical progression. Treatments could also be discontinued at the time of confirmed radiographic progression at the discretion of the investigator. Patients should not be discontinued based on PSA progression alone and should remain on treatment until fully confirmed clinical progression utilising multiple assessment criteria.
Radiographic progression free survival was assessed with the use of sequential imaging studies as defined by PCWG2 criteria (for bone lesions) and modified Response Evaluation Criteria in Solid Tumours (RECIST) criteria (for soft tissue lesions). PCWG2 criteria require a confirmatory bone scan to document progression. Analysis of rPFS utilised centrally reviewed radiographic assessment of progression.
At the planned rPFS analysis there were 401 radiographic progression events; 150 (28%) of patients treated with abiraterone and 251 (46%) of patients treated with placebo had radiographic evidence of progression or had died. A significant difference in rPFS between treatment groups was observed (see Table 6 and Figure 4).
Subgroup analyses of rPFS are presented in Figure 5. The treatment effect of abiraterone on the coprimary endpoint of the independent review of rPFS was consistently favourable and highly robust across all subgroups.
A planned interim analysis for overall survival was conducted after 333 deaths were observed. The study was unblinded, following the recommendation of the Independent Data Monitoring Committee (IDMC), based on the magnitude of clinical benefit observed. Twenty seven percent (147 of 546) of patients treated with abiraterone, compared with 34% (186 of 542) of patients treated with placebo, had died. Overall survival was longer for abiraterone than placebo with a 25% reduction in risk of death (Hazard Ratio = 0.752; 95% CI: 0.606 - 0.934). The p value was 0.0097 which did not meet the pre-specified level (0.0008) to claim statistical significance (see Table 7 and Figure 6).
Subgroup analyses of overall survival are presented in Figure 7. The treatment effect of abiraterone on overall survival was favorable across all subgroups (all HR < 1.0).
In addition to the observed improvements in overall survival and rPFS, benefit was demonstrated for abiraterone versus placebo treatment in all the secondary endpoint measures as follows.
Time to PSA progression based on PCWG2 criteria. Median time to PSA progression was 11.1 months for patients receiving abiraterone and 5.6 months for patients receiving placebo (HR=0.488; 95%CI: [0.420, 0.568], p < 0.0001). Time to PSA progression was approximately doubled with abiraterone treatment. The proportion of subjects with a confirmed PSA response was greater in the abiraterone group than in the placebo group (62% versus 24%; p < 0.0001).
Time to opiate use for cancer pain. The median time to opiate use for prostate cancer pain was not reached for patients receiving abiraterone and was 23.7 months for patients receiving placebo (HR=0.686; 95%CI: [0.566, 0.833], p=0.0001).
Time to initiation of cytotoxic chemotherapy. The median time to initiation of cytotoxic chemotherapy was 25.2 months for patients receiving abiraterone and 16.8 months for patients receiving placebo (HR=0.580; 95% CI: [0.487, 0.691], p < 0.0001).
Time to deterioration in ECOG performance score by ≥ 1 point. The median time to deterioration in ECOG performance score by ≥ 1 point was 12.3 months for patients receiving abiraterone and 10.9 months for patients receiving placebo (HR=0.821; 95% CI: [0.714, 0.943], p=0.0053).
The following study endpoints demonstrated a statistically significant advantage in favour of abiraterone treatment.
Objective response. Objective response was defined as the proportion of subjects with measurable disease achieving a complete or partial response according to RECIST criteria (baseline lymph node size was required to be ≥ 2 cm to be considered a target lesion). The proportion of subjects with measurable disease at baseline who had an objective response was 36% in the abiraterone group and 16% in the placebo group (p < 0.0001).
Pain. Treatment with abiraterone significantly reduced the risk of average pain intensity progression by 18% compared with placebo (p=0.0490). The median time to progression was 26.7 months in the abiraterone group and 18.4 months in the placebo group.
Time to degradation in the FACT-P (total score). Treatment with abiraterone decreased the risk of FACT-P (Total Score) degradation by 22% compared with placebo (p=0.0028). The median time to degradation in FACT-P (total score) was 12.7 months in the abiraterone group and 8.3 months in the placebo group.
Study 301 (patients who had received prior chemotherapy. Eleven percent of patients enrolled in study 301 had an ECOG performance score of 2; 70% had radiographic evidence of disease progression with or without PSA progression; 70% had received one prior cytotoxic chemotherapy and 30% received two. Liver metastasis was present in 11% of patients treated with abiraterone.
It was recommended that patients be maintained on their study drugs until there was PSA progression (confirmed 25% increase over the patient's baseline/nadir) together with protocol-defined radiographic progression and symptomatic or clinical progression. The primary efficacy endpoint was overall survival.
In a planned analysis conducted after 552 deaths were observed, 42% (333 of 797) of patients treated with abiraterone compared with 55% (219 of 398) of patients treated with placebo had died. A statistically significant improvement in median overall survival was seen in patients treated with abiraterone (see Table 8).
At all evaluation time points after the initial few months of treatment, a higher proportion of patients treated with abiraterone remained alive compared with the proportion of patients treated with placebo (see Figure 8).
Subgroup survival analyses showed a consistent survival benefit for treatment with abiraterone (see Figure 9).
In addition to the observed improvement in overall survival, all secondary study endpoints favoured abiraterone and were statistically significant after adjusting for multiple testing as follows.
Patients receiving abiraterone demonstrated a significantly higher total PSA response rate (defined as a ≥ 50% reduction from baseline), compared with patients receiving placebo: 29% versus 6%, p < 0.0001.
The median time to PSA progression was 10.2 months for patients treated with abiraterone and 6.6 months for patients treated with placebo (HR= 0.580; 95% CI: [0.462, 0.728], p < 0.0001).
The median radiographic progression free survival was 5.6 months for patients treated with abiraterone and 3.6 months for patients who received placebo (HR= 0.673; 95% CI: [0.585, 0.776], p < 0.0001).
Pain. The proportion of patients with pain palliation was statistically significantly higher in the abiraterone group than in the placebo group (44% versus 27%, p=0.0002).
A lower proportion of patients treated with abiraterone had pain progression compared to patients taking placebo at 6 (22% vs. 28%), 12 (30% vs. 38%) and 18 months (35% vs. 46%). The time to pain progression at the 25th percentile was 7.4 months in the abiraterone group, versus 4.7 months in the placebo group.
Skeletal-related events. A lower proportion of patients in the abiraterone group had skeletal-related events compared with the placebo group at 6 months (18% vs. 28%), 12 months (30% vs 40%), and 18 months (35% vs. 40%). The time to first skeletal-related event at the 25th percentile in the abiraterone group was twice that of the control group at 9.9 months vs 4.9 months.

5.2 Pharmacokinetic Properties

Following administration of abiraterone acetate, the pharmacokinetics of abiraterone has been studied in healthy subjects, patients with metastatic advanced prostate cancer and subjects without cancer with hepatic or renal impairment. Abiraterone acetate is rapidly converted in vivo to abiraterone (see Section 5.1 Pharmacodynamic Properties).
Absorption. Following oral administration of abiraterone acetate in the fasting state, the median time to reach maximum plasma abiraterone concentration is approximately 2 hours.
Effect of food on absorption. Administration of abiraterone acetate with food, compared with administration in a fasted state, results in up to a 17-fold increase in mean systemic exposure of abiraterone depending on the fat content of the meal. Given the normal variation in the content and composition of meals, taking ARX-Abiraterone with meals has the potential to result in highly variable exposures. therefore, ARX-Abiraterone must not be taken with food. ARX-Abiraterone must be taken as a single dose once daily on an empty stomach. ARX-Abiraterone must be taken at least two hours after eating and food must not be eaten for at least one hour after taking ARX-Abiraterone. The tablets must be swallowed whole with water (see Section 4.2 Dose and Method of Administration).
Distribution. The plasma protein binding of ¹⁴C abiraterone in human plasma is 99.8%. The apparent volume of distribution is approximately 5630 L, suggesting that abiraterone extensively distributes to peripheral tissues.
Metabolism. Following oral administration of ¹⁴C-abiraterone acetate as capsules, abiraterone acetate is hydrolysed to abiraterone, which then undergoes metabolism including sulphation, hydroxylation and oxidation primarily in the liver. The majority of circulating radioactivity (approximately 92%) is found in the form of metabolites of abiraterone. Of 15 detectable metabolites, 2 main metabolites, abiraterone sulphate and N-oxide abiraterone sulphate, each represent approximately 43% of total radioactivity.
The major enzymes involved in the metabolism of abiraterone are CYP3A4 for phase I (oxidative) metabolites, the sulfotransferase (SULT) isozyme SULT2A1, and UDP-glucuronosyl transferase (UGT) UGT1A4. No studies have been conducted to determine if drugs that induce or inhibit these enzymes affect the metabolism of abiraterone.
Excretion. The mean half-life of abiraterone in plasma is approximately 15 hours based on data from healthy subjects. Following oral administration of ¹⁴C abiraterone acetate, approximately 88% of the radioactive dose is recovered in faeces and approximately 5% in urine. The major compounds present in faeces are unchanged abiraterone acetate and abiraterone (approximately 55% and 22 % of the administered dose, respectively).
Additional information on special populations. Hepatic impairment. The pharmacokinetics of abiraterone was examined in subjects with pre-existing mild or moderate hepatic impairment (Child-Pugh class A and B, respectively) and in healthy control subjects. Systemic exposure to abiraterone after a single oral 1 g dose increased by approximately 11% and 260% in subjects with mild and moderate pre-existing hepatic impairment, respectively. The mean half-life of abiraterone is prolonged to approximately 18 hours in subjects with mild hepatic impairment and to approximately 19 hours in subjects with moderate hepatic impairment. No dosage adjustment is necessary for patients with pre-existing mild hepatic impairment. There are no data on the clinical safety and efficacy of multiple doses of abiraterone acetate when administered to patients with moderate or severe hepatic impairment (Child-Pugh Class B or C). No dose adjustment can be predicted. ARX-Abiraterone should be used with caution in patients with moderate hepatic impairment, only if the benefit clearly outweighs the possible risk. ARX-Abiraterone should not be used in patients with pre-existing severe hepatic impairment (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use; Section 4.2 Dose and Method of Administration).
For patients who develop hepatotoxicity during treatment with abiraterone suspension of treatment and dosage adjustment may be required (see Section 4.4 Special Warnings and Precautions for Use; Section 4.2 Dose and Method of Administration).
Renal impairment. The pharmacokinetics of abiraterone was compared in patients with end-stage renal disease on a stable haemodialysis schedule versus matched control subjects with normal renal function. Systemic exposure to abiraterone after a single oral 1 g dose did not increase in patients with end-stage renal disease on dialysis. Administration of abiraterone in patients with renal impairment including severe renal impairment does not require dose reduction (see Section 4.2 Dose and Method of Administration).

5.3 Preclinical Safety Data

Genotoxicity. Abiraterone acetate and abiraterone were devoid of genotoxic potential in the standard panel of genotoxicity tests including, an in vitro bacterial reverse mutation assay (the Ames test), an in vitro mammalian chromosome aberration test (using human lymphocytes) and an in vivo rat micronucleus assay. Genotoxicity studies have not been conducted with the main human metabolites of abiraterone.
Carcinogenicity. Carcinogenicity studies were not conducted with abiraterone acetate.
* All safety data from studies co-administering abiraterone with prednisone alone or prednisone/prednisolone have been included in the PI to ensure completeness of safety information. This safety information is applicable to coadministration of ARX-Abiraterone with prednisolone.

6 Pharmaceutical Particulars

6.1 List of Excipients

The tablets also contain the inactive ingredients:
250 mg tablet contains: lactose monohydrate; microcrystalline cellulose; croscarmellose sodium; povidone; sodium lauryl sulfate; magnesium stearate, silicon dioxide, macrogol 400, titanium dioxide and hypromellose.
500 mg tablet contains: lactose monohydrate, silicified microcrystalline cellulose croscarmellose sodium, sodium lauryl sulfate, magnesium stearate, hypromellose, colloidal anhydrous silica.
The tablet coating of the 500 mg tablet contains: Opadry II Purple 85F500067.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

ARX-Abiraterone 250 mg tablets. Store below 25°C.
ARX-Abiraterone 500 mg tablets. Store below 30°C.

6.5 Nature and Contents of Container

ARX-Abiraterone 250 mg tablets are provided in high density polyethylene white bottles fitted with a child-resistant polypropylene cap. A bottle contains 120 tablets.
ARX-Abiraterone 500 mg tablets are available in (PVC/PCTFE (Aclar)/Al blister packs of 60 tablets.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.

Chemical name: 3β-Acetoxy-17-(3-pyridyl)-androsta-5,16-diene.
Molecular formula: C₂₆H₃₃NO₂.
Molecular weight: 391.55.
CAS number. 154229-18-2.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Date of First Approval

06 August 2025

Date of Revision

06 August 2025

Summary Table of Changes