Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: HETERAN 250  
Dosage form and strength: Film Coated Tablet and 250 mg  
PROFESSIONAL INFORMATION FOR HETERAN 250  
SCHEDULING STATUS  
S4  
1 NAME OF THE MEDICINE  
HETERAN 250, 250 mg (film coated tablets)  
2 QUALITATIVE AND QUANTITATIVE COMPOSITION  
Each tablet contains 250 mg abiraterone acetate.  
HETERAN 250 contains sugar lactose monohydrate (126,600 mg).  
Each tablet contains 24,000 mg of sodium lauryl sulfate and 45,000 mg of croscarmellose sodium.  
For a full list of excipients, see section 6.1.  
3 PHARMACEUTICAL FORM  
White coloured, oval shaped, film coated tablets debossed with ‘H’ on one side and ‘A1’ on the other side,  
free from physical defects.  
4 CLINICAL PARTICULARS  
4.1 Therapeutic indications  
HETERAN 250 is indicated with low-dose corticosteroids (prednisone or prednisolone) in adults for the  
treatment of:  
•
high-risk metastatic hormone treatment naive prostate cancer (mHNPC) or newly diagnosed high-  
risk metastatic hormone sensitive prostate cancer (mHSPC) in combination with androgen  
deprivation therapy (LHRH agonist or surgical castration).  
High-risk is defined as having at least 2 of the following 3 risk factors:  
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(1) Gleason score of ≥ 8;  
(2) presence of 3 or more bone lesions;  
(3) presence of measurable visceral (excluding lymph node disease) metastasis.  
•
•
metastatic castration resistant prostate cancer with bone metastases who are asymptomatic or  
mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet  
clinically indicated.  
metastatic advanced prostate cancer (castration resistant prostate cancer) who have received prior  
chemotherapy containing docetaxel.  
4.2 Posology and method of administration  
Posology  
The recommended dose of HETERAN 250 is 1 g (four 250 mg tablets) as a single daily dose that must not  
be taken with food. Taking HETERAN 250 with food increases systemic exposure to abiraterone (see  
sections 4.5 and 5.2).  
Patients should be maintained on HETERAN 250 until radiographic progression and symptomatic/clinical  
progression and until PSA progression (confirmed 25 % increase over the patient's baseline/nadir).  
Dosage of prednisone or prednisolone  
For metastatic hormone naive prostate cancer (mHNPC) or hormone sensitive prostate cancer (mHSPC),  
HETERAN 250 is used with 5 mg prednisone or prednisolone once daily.  
For metastatic castration-resistant prostate cancer (mCRPC), HETERAN 250 is used with 10 mg prednisone  
or prednisolone daily.  
Recommended monitoring  
Serum transaminases and bilirubin should be measured prior to starting treatment with HETERAN 250,  
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Dosage form and strength: Film Coated Tablet and 250 mg  
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).  
In the event of a missed daily dose of either HETERAN 250, prednisone or prednisolone, treatment should  
be resumed the following day with the usual daily dose.  
Hepatic impairment:  
No dose adjustment is necessary for patients with pre-existing mild hepatic impairment, Child-Pugh class A.  
There are no data on the clinical safety and efficacy of multiple doses of HETERAN 250 when administered  
to patients with moderate or severe hepatic impairment (Child Pugh Class B or C). No dose adjustment can  
be predicted. HETERAN 250 should not be used in patients with moderate to severe hepatic impairment  
(see section 4.3).  
For patients who develop hepatotoxicity during treatment with HETERAN 250 (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 are back to pre-treatment status (see section 4.4). Retreatment following return of liver  
function tests to the patient's baseline may be given at a reduced dose of 500 mg once daily. For patients  
being re-treated, serum transaminases and bilirubin should be monitored at a minimum of every two weeks  
for the first three months and monthly thereafter. If hepatotoxicity recurs at the reduced dose of 500 mg daily,  
treatment should be discontinued. Reduced doses should not be taken with food (see previous).  
If patients develop severe hepatotoxicity (ALT or AST 20 times the upper limit of normal) anytime while on  
therapy, HETERAN 250 should be discontinued and patients should not be retreated with HETERAN 250.  
Renal impairment:  
No dose adjustment is necessary for patients with renal impairment (see section 5.2).  
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Paediatric population:  
There is no relevant use of HETERAN 250 in paediatric patients, as prostate cancer is not present in the  
paediatric population.  
Method of administration  
HETERAN 250 is for oral use.  
HETERAN 250 must be taken on an empty stomach, at least one hour before or at least two hours after a  
meal. The tablets should be swallowed whole with water.  
Precautions to be taken before handling or administering HETERAN 250 (see section 6.6).  
Based on its mechanism of action, HETERAN 250 may harm a developing foetus; therefore, women  
(including healthcare professionals), who are pregnant or women who may be pregnant should not handle  
HETERAN 250 250 mg tablets without protection, e.g. gloves (see sections 4.6 and 6.6).  
4.3 Contraindications  
HETERAN 250 is contraindicated in:  
•
•
•
•
•
•
Patients with hypersensitivity to abiraterone acetate or to any of the excipients listed in section 6.1.  
Pregnancy and Lactation (see section 4.6).  
Moderate to severe hepatic impairment (see sections 4.2, 4.4 and 5.2).  
Women should not use HETERAN 250.  
Women who are pregnant, trying to get pregnant or may potentially be pregnant (see section 4.6).  
Concomitant administration with rifampicin (see section 4.5).  
4.4 Special warnings and precautions for use  
Hypertension, hypokalaemia and fluid retention due to mineralocorticoid excess  
HETERAN 250 may cause hypertension, hypokalaemia and fluid retention (see section 4.8) as a  
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consequence of increased mineralocorticoid levels resulting from CYP17 inhibition (see section 5.1). Co-  
administration of a corticosteroid suppresses adrenocorticotropic hormone (ACTH) drive, resulting in a  
reduction in incidence and severity or these adverse reactions. Blood pressure, serum potassium and fluid  
retention should be monitored at least monthly. 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, severe or unstable angina pectoris, recent myocardial infarction or ventricular  
dysrhythmia and those with severe renal impairment.  
HETERAN 250 should be used with caution in patients with a history of cardiovascular disease. The safety  
of HETERAN 250 in patients with left ventricular ejection fraction < 50 % or NYHA Class Ill or IV heart failure  
has not been established (see section 4.8). Before treatment with HETERAN 250, hypertension must be  
controlled and hypokalaemia must be corrected.  
Before treating patients with a significant risk for congestive heart failure (e.g. a history of cardiac failure,  
uncontrolled hypertension, or cardiac events such as ischaemic heart disease), consider obtaining an  
assessment of cardiac function (e.g. echocardiogram). Before treatment with HETERAN 250, cardiac failure  
should be treated and cardiac function optimised.  
Hypertension, hypokalaemia and fluid retention should be corrected and controlled. During treatment, blood  
pressure, serum potassium, fluid retention (weight gain, peripheral oedema), and other signs and symptoms  
of congestive heart failure should be monitored every 2 weeks for 3 months, then monthly thereafter and  
abnormalities corrected. QT prolongation has been observed in patients experiencing hypokalaemia in  
association with HETERAN 250 treatment. Assess cardiac function as clinically indicated, institute  
appropriate management and consider discontinuation of this treatment if there is a clinically significant  
decrease in cardiac function (see section 4.2).  
Hepatotoxicity and hepatic impairment  
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Marked increases in liver enzymes leading to HETERAN 250 discontinuation or dose modification occurred  
in controlled clinical studies (see section 4.8). Serum transaminase and bilirubin levels should be measured  
prior to starting treatment with HETERAN 250, 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 HETERAN 250 should be  
interrupted immediately and liver function closely monitored.  
Re-treatment with HETERAN 250 may take place only after return of liver function tests to the patient's  
baseline and at a reduced dose level (see section 4.2).  
If patients develop severe hepatotoxicity (ALT or AST 20 times the upper limit of normal) anytime while on  
therapy, HETERAN 250 should be permanently discontinued and patients should not be re-treated with  
HETERAN 250.  
There are no data on the clinical safety and efficacy of multiple doses of HETERAN 250 when administered  
to patients with moderate or severe hepatic impairment (Child Pugh Class B or C). HETERAN 250 should  
not be used in patients with moderate to severe hepatic impairment (see section 4.3).  
There are no data to support the use of HETERAN 250 in patients with active or symptomatic viral hepatitis.  
Acute liver failure and fulminant hepatitis, some with fatal outcome have been reported (see section 4.8).  
Corticosteroid withdrawal and coverage of stress situations  
Caution is advised and monitoring for adrenocortical insufficiency should occur if patients need to be  
withdrawn from prednisone or prednisolone. If HETERAN 250 is continued after corticosteroids are  
withdrawn, patients should be monitored for symptoms of mineralocorticoid excess (see previous).  
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Product proprietary name: HETERAN 250  
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In patients on prednisone or prednisolone who are subjected to unusual stress, increased dosage of  
corticosteroids may be indicated before, during and after the stressful situation.  
Bone density  
Decreased bone density may occur in men with metastatic advanced prostate cancer. The use of HETERAN  
250 in combination with a glucocorticoid could increase this effect.  
Use with chemotherapy  
The safety and efficacy of concomitant use of HETERAN 250 with cytotoxic chemotherapy has not been  
established.  
Use in combination with radium 223 dichloride  
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 is not recommended for use  
in combination with HETERAN 250 plus prednisone/prednisolone, showed an increase in mortality and an  
increased rate of fracture.  
Prior use of ketoconazole  
Lower rates of response might be expected in patients previously treated with ketoconazole for prostate  
cancer.  
Hyperglycaemia  
The use of glucocorticoids could increase hyperglycaemia, therefore blood sugar should be measured  
frequently in patients with diabetes.  
Potential risks  
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Anaemia and sexual dysfunction may occur in men with metastatic prostate cancer, including those  
undergoing treatment with HETERAN 250.  
Skeletal muscle effects  
Cases of myopathy have been reported in patients treated with HETERAN 250. Some patients had  
rhabdomyolysis with renal failure. Most cases developed within the first 6 months of treatment and recovered  
after HETERAN 250 withdrawal. Caution is recommended in patients concomitantly treated with medicinal  
products known to be associated with myopathy/rhabdomyolysis.  
Interactions with other medicines  
Strong inducers of CYP3A4 during treatment are to be avoided unless there is no therapeutic alternative,  
due to risk of decreased exposure to HETERAN 250 (see section 4.5).  
Lactose  
HETERAN 250 contains lactose. Patients with rare hereditary problems of galactose intolerance, total  
lactase deficiency or glucose-galactose malabsorption should not take HETERAN 250.  
HETERAN 250 also contains sodium. To be taken into consideration by patients on a controlled sodium diet.  
4.5 Interaction with other medicines and other forms of interaction  
Effect of food on HETERAN 250:  
Administration of HETERAN 250 with food significantly increases the absorption of abiraterone acetate. The  
efficacy and safety of HETERAN 250 given with food have not been established. HETERAN 250 must not  
be taken with food (see sections 4.2 and 5.2).  
Interaction with other medicines  
Potential for other medicines to affect HETERAN 250 exposures  
In a clinical pharmacokinetic interaction study of healthy subjects pretreated with a strong CYP3A4 inducer  
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(rifampicin, 600 mg daily for 6 days) followed by a single dose of abiraterone as in HETERAN 250 1 000 mg,  
the mean plasma AUC∞ of abiraterone was decreased by 55 % (see section 4.3).  
Other strong inducers of CYP3A4 (e.g. phenytoin, carbamazepine, rifabutin, rifapentine, phenobarbitone,  
St.John’s wort) during treatment with HETERAN 250 are to be avoided.  
It was reported that in a separate clinical pharmacokinetic interaction study of healthy subjects, co-  
administration of ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the  
pharmacokinetics of abiraterone as in HETERAN 250.  
Potential for HETERAN 250 to affect exposures to other medicines  
Abiraterone as in HETERAN 250 is an inhibitor of the hepatic medicine-metabolising enzymes CYP2D6 and  
CYP2C8. It was reported that in a clinical 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 by approximately 200 %. The AUC24 for dextrorphan, the active metabolite  
of dextromethorphan, increased approximately 33 %.  
Caution is advised when HETERAN 250 is administered with medicines activated by or metabolised by  
CYP2D6, particularly with medicines that have a narrow therapeutic index. Dose reduction of narrow  
therapeutic index medicines metabolised by CYP2D6 should be considered (e.g.metoprolol, propranolol,  
desipramine, venlafaxine, paroxetine, propafenone, flecainide, haloperidol, risperidone, codeine, oxycodone  
and tramadol).  
In the same study to determine the effects of HETERAN 250 (plus prednisone) on a single dose of the  
CYP1A2 substrate theophylline, no increase in systemic exposure of theophylline was observed).  
It was reported that in a CYP2C8 interaction trial in healthy subjects, the AUC of pioglitazone was increased  
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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 1 000 mg HETERAN 250. Patients should be  
monitored for signs of toxicity related to CYP2C8 substrate with a narrow therapeutic index if used  
concomitantly with HETERAN 250.  
In vitro, the major metabolites abiraterone sulphate and N-oxide abiraterone sulphate were shown to inhibit  
the hepatic uptake transporter OATP1B1 and as a consequence it may increase the concentrations of  
medicinal products eliminated by OATP1B1.  
Use with products known to prolong QT interval  
Since androgen deprivation treatment may prolong the QT interval, caution is advised when administering  
HETERAN 250 with medicinal products known to prolong the QT interval or medicinal products able to  
induce torsades de pointes such as class IA (e.g. quinidine, disopyramide) or class III (e.g. amiodarone,  
sotalol, dofetilide, ibutilide) antidysrhythmic medicinal products, methadone, moxifloxacin, antipsychotics,  
etc.  
Concomitant use with Spironolactone  
Spironolactone binds to the androgen receptor and may increase prostate specific antigen (PSA) levels. Use  
with HETERAN 250 is not recommended.  
Concomitant use with eplenerone  
There is no clinical study data related to concomitant use of eplenerone with HETERAN 250.  
4.6 Fertility, pregnancy and lactation  
Women should not use HETERAN 250.  
Women of childbearing potential  
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There are no human data on the use of HETERAN 250 in pregnancy and HETERAN 250 is not for use in  
women of childbearing potential. Maternal use of a CYP17 inhibitor is expected to produce changes in  
hormone levels that could affect development of the foetus.  
Contraception in males and females  
Animal studies have shown reproductive toxicity.  
It is not known whether 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  
childbearing potential, a condom is required along with another effective contraceptive method until one  
week after the last dose of HETERAN 250.  
Pregnancy  
HETERAN 250 is contraindicated in women who are or may potentially be pregnant (see section 4.3).  
Pregnant women or women of child-bearing potential should handle HETERAN 250 with gloves.  
Breastfeeding  
HETERAN 250 is not for use in women. It is not known if either abiraterone acetate or its metabolites are  
excreted in human breast milk.  
Fertility  
In fertility studies in both male and female rats, abiraterone as in HETERAN 250 reduced fertility, which was  
completely reversible in 4 to 16 weeks after abiraterone as in HETERAN 250 was stopped.  
It is recommended to store semen before starting treatment with HETERAN 250 in patients who might want  
to father a child.  
4.7 Effects on ability to drive and use machines  
HETERAN 250 may affect the ability of patients to drive or use machines. Patients should not drive and use  
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machines before they know how treatment with HETERAN 250 affects their ability to drive and use  
machines.  
4.8 UNDESIRABLE EFFECTS  
a) Summary of the safety profile  
HETERAN 250 may cause hypertension, hypokalaemia and fluid retention as a pharmacodynamic  
consequence of its mechanism of action.  
b) Tabulated summary of clinical adverse reactions  
Infections and infestations  
Frequent: Urinary tract infection, sepsis  
Endocrine disorders  
Less frequent: Adrenal insufficiency  
Metabolism and nutrition disorders  
Frequent: Hypokalaemia, hypertriglyceridaemia  
Cardiac disorders  
Frequent: Cardiac failure (including congestive heart failure, left ventricular dysfunction and decreased left  
ventricular ejection fraction), angina pectoris, atrial fibrillation, tachycardia  
Less frequent: Dysrhythmia  
Frequency unknown: Myocardial infarction, QT prolongation (see sections 4.4 and 4.5)  
Vascular disorders  
Frequent: Hypertension  
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Respiratory, thoracic and mediastinal disorders  
Less frequent: Allergic alveolitis  
Gastrointestinal disorders  
Frequent: Diarrhoea, dyspepsia  
Hepato-biliary disorders  
Frequent: Hepatotoxicity, abnormal hepatic functions including elevated hepatic function tests such as alanine  
aminotransferase (ALT), aspartate aminotransferase (AST), aspartate aminotransferase (AST) and total  
bilirubin  
Less frequent: Hepatitis fulminant, acute hepatic failure  
Skin and subcutaneous tissue disorders  
Frequent: Rash  
Musculoskeletal and connective tissue disorders  
Frequent: Fractures (includes osteoporosis and all fractures with the exception of pathological fractures)  
Less frequent: Myopathy, rhabdomyolysis  
Renal and urinary disorders  
Frequent: Haematuria  
Less frequent: Renal failure (secondary to rhabdomyolysis)  
General disorders and administrative site conditions  
Frequent: Peripheral oedema  
Investigations  
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Frequent: Increased alanine aminotransferase (ALT), increased aspartate transaminase (AST)  
Reporting of suspected adverse reactions  
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued  
monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any  
suspected adverse reactions via the “6.04 Adverse Drug Reactions Reporting Form”, found online under  
SAHPRA’s publications: https://www.sahpra.org.za/publications/Index/8 or to the Holder of certificate of  
registration through the mail: pvg.cdma@heterogroups.com.  
4.9 Overdose  
In overdose, the undesirable effects can be precipitated and/or be of increased severity (see section 4.8).  
There is no specific antidote. Treatment with HETERAN 250 must be discontinued. Treatment is  
symptomatic and supportive which includes relevant monitoring of cardiac and hepatic function, serum  
potassium and blood pressure.  
5 PHARMACOLOGICAL PROPERTIES  
5.1 Pharmacodynamic properties  
Pharmacological classification  
A.21.12 Hormone inhibitors  
Mechanism of action  
Abiraterone acetate is converted in vivo to abiraterone, an androgen biosynthesis inhibitor. 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 prostatic tumour tissues. CYP17 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).  
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Androgen sensitive prostatic carcinoma responds to treatment that decreases androgen levels. Androgen  
deprivation therapies, such as treatment with LHRH (luteinizing hormone releasing hormone) 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 acetate decreases serum testosterone to undetectable  
levels (using commercial assays) when given with LHRH agonists (or orchiectomy).  
Pharmacodynamic effects  
Prostate specific antigen (PSA) serves as a biomarker in patients with prostate cancer. It was reported that  
in a phase 3 clinical study of patients who failed prior chemotherapy with taxanes, 38 % of patients treated  
with abiraterone acetate, versus 10 % of patients treated with placebo, had at least a 50 % decline from  
baseline in PSA levels.  
5.2 Pharmacokinetic properties  
It was reported that following administration or abiraterone acetate, the pharmacokinetics of abiraterone and  
abiraterone acetate have 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, an androgen biosynthesis inhibitor (see section 5.1).  
Absorption  
Following oral administration of abiraterone acetate in the fasting state, the time to reach maximum plasma  
abiraterone concentration is approximately 2 hours.  
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 abiraterone acetate with meals  
has the potential to result in highly variable exposures. Therefore, abiraterone acetate must not be taken  
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Dosage form and strength: Film Coated Tablet and 250 mg  
with food.  
Abiraterone acetate should be taken at least two hours after eating and no food should be eaten for at least  
one hour after taking HETERAN 250. The tablets should be swallowed whole with water (see section 4.2).  
Distribution  
The plasma protein binding of 14C-abiraterone in human plasma is 99,8 %. The apparent volume of  
distribution is approximately 5 630 L, suggesting that abiraterone extensively distributes to peripheral  
tissues.  
Biotransformation  
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 represents approximately 43 % of total radioactivity.  
Elimination  
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 1 g, 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).  
Patients with hepatic impairment  
The pharmacokinetics of abiraterone acetate 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  
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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 dose adjustment is necessary for patients with pre-existing  
mild hepatic impairment.  
Abiraterone acetate should not be used in patients with moderate to severe hepatic impairment (see section  
4.3).  
There are no data on the clinical safety and efficacy of multiple doses of abiraterone when administered to  
patients with moderate or severe hepatic impairment (Child Pugh Class B or C). No dose adjustment can be  
predicted. Abiraterone acetate should not be used in patients with moderate to severe hepatic impairment  
(see section 4.3).  
For patients who develop hepatotoxicity during treatment with abiraterone acetate, suspension of treatment  
and dose adjustment may be required (see sections 4.2 and 4.4).  
Patients with renal impairment  
The pharmacokinetics of abiraterone acetate 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 subjects with end-stage renal disease  
on dialysis. Administration of abiraterone acetate in patients with renal impairment, including severe renal  
impairment, does not require dose reduction (see section 4.2).  
5.3 Preclinical safety data  
In all animal toxicity studies, circulating testosterone levels were significantly reduced. As a result, reduction  
in organ weights and morphological and/or histopathological changes in the reproduction organs, and the  
adrenal, pituitary and mammary glands were observed. All changes showed complete or partial reversibility.  
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The changes in the reproductive organs and androgen-sensitive organs are consistent with the  
pharmacology of abiraterone.  
In fertility studies in both male and female rats, abiraterone acetate reduced fertility, which was completely  
reversible in 4 to 16 weeks after abiraterone acetate was stopped.  
In a developmental toxicity study in the rat, abiraterone acetate affected pregnancy including reduced foetal  
weight and survival. Effects on the external genitalia 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.  
Aside from reproductive organ changes seen in all animal toxicology studies, non-clinical data reveal no  
special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity,  
genotoxicity and carcinogenic potential.  
Environmental Risk Assessement  
Abiraterone as in HETERAN 250, shows an environmental risk for the aquatic environment, especially to  
fish.  
6 PHARMACEUTICAL PARTICULARS  
6.1 List of excipients  
Colloidal silicon dioxide  
Croscarmellose sodium  
Lactose monohydrate  
Magnesium stearate  
Silicified Microcrystalline cellulose  
Hypromellose  
Sodium lauryl sulfate  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: HETERAN 250  
Dosage form and strength: Film Coated Tablet and 250 mg  
Film coating  
Opadry II White 85F18422 (Composition: Titanium Dioxide, Macrogol/Peg and Talc)  
6.2 Incompatibilities  
Not applicable  
6.3 Shelf life  
24 months  
6.4 Special precautions for storage  
Store at or below 25 °C. Keep well closed.  
Protect from light and moisture.  
This medicine does not require any special storage conditions.  
6.5 Nature and contents of container  
Tablets are packed in a white opaque high density polyethylene (HDPE) container with a white opaque child  
resistant plastic cap with a pulp liner.  
Pack size: 120 tablets  
Keep the bottle in the outer carton until required for use.  
6.6 Special precautions for disposal and other handling  
Precautions to be taken before handling or administering HETERAN 250. Based on its mechanism of action,  
abiraterone as in HETERAN 250 may harm a developing foetus.  
Women (including healthcare providers) who are pregnant or women who may be pregnant should not  
handle HETERAN 250 without protection, e.g. gloves (see section 4.6).  
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Page 19 of 20  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: HETERAN 250  
Dosage form and strength: Film Coated Tablet and 250 mg  
Any unused medicine should be returned to the pharmacy to be correctly disposed of in accordance with  
local requirements. This medicine may pose a risk to the aquatic environment (see section 5.3).  
7 HOLDER OF CERTIFICATE OF REGISTRATION  
Hetero Drugs South Africa (Pty) Ltd  
Waterfall Corporate Campus,  
Building No.2, First Floor,  
74 Waterfall Drive,  
Midrand, 2066  
Telephone number: 012 644 1220  
e-mail address: nokuthula.n@hetero.com  
8 REGISTRATION NUMBER(S)  
51/21.12/1131.130  
9 DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION  
22 June 2021  
10 DATE OF REVISION OF THE TEXT  
27 October 2025  
27 October 2025  
Initial: K.B  
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