Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: BICALUTAMIDE 50 mg HETERO  
Dosage form and strength: Film coated tablet and 50 mg  
PROPOSED PROFESSIONAL INFORMATION FOR BICALUTAMIDE 50 mg HETERO  
SCHEDULING STATUS: S4  
1 NAME OF THE MEDICINAL PRODUCT  
BICALUTAMIDE 50 mg HETERO (film coated tablets)  
2 QUALITATIVE AND QUANTITATIVE COMPOSITION  
Each film coated tablet contains 50 mg bicalutamide.  
Contains sugar (lactose monohydrate 61 mg)  
For the full list of excipients, see section 6.1.  
3 PHARMACEUTICAL FORM  
White colored, round shaped biconvex, film coated tablets, debossed with '2' on one side and 'H' on  
the other side.  
4. CLINICAL PARTICULARS  
4.1 Therapeutic indications  
Treatment of advanced prostate cancer in combination with Luteinising Hormone Releasing Hormone  
(LHRH) analogue therapy or surgical castration.  
4.2 Posology and method of administration  
Posology  
Adults males including the elderly:  
One tablet (50 mg) once daily.  
Treatment with BICALUTAMIDE 50 mg HETERO should be started at least three days before  
commencing with a LHRH analogue, or at the same time as surgical castration.  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: BICALUTAMIDE 50 mg HETERO  
Dosage form and strength: Film coated tablet and 50 mg  
Renal impairment:  
No dosage adjustment is necessary for patients with renal impairment.  
Hepatic impairment:  
No dosage adjustment is necessary for patients with mild hepatic impairment. Increased accumulation  
may occur in patients with moderate to severe hepatic impairment (see section 4.4)  
Method of administration  
BICALUTAMIDE 50 mg HETERO is for oral use.  
4.3 Contraindications  
•
BICALUTAMIDE 50 mg HETERO must not be given to any patient who has shown a  
hypersensitivity reaction to the bicalutamide or to any of the excipients of BICALUTAMIDE 50  
mg HETERO listed in section 6.1.  
•
•
BICALUTAMIDE 50 mg HETERO is contraindicated in females and adolescents under the  
age of 18 years (see section 4.6).  
Co-administration of terfenadine, astemizole or cisapride with bicalutamide (see section 4.5).  
4.4 Special warnings and precautions for use  
Initiation of BICALUTAMIDE 50 mg HETERO treatment should be under the direct supervision of a  
medical practitioner qualified in the use of anti-cancer chemotherapy.  
Bicalutamide as in BICALUTAMIDE 50 mg HETERO is extensively metabolised in the liver. Data  
suggests that its elimination may be slower in subjects with severe hepatic impairment and this could  
lead to increased accumulation of bicalutamide. Therefore, BICALUTAMIDE 50 mg HETERO should  
be used with caution in patients with moderate to severe hepatic impairment.  
M.R  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: BICALUTAMIDE 50 mg HETERO  
Dosage form and strength: Film coated tablet and 50 mg  
Periodic liver function testing should be considered due to the possibility of hepatic changes. The  
majority of changes are expected to occur within the first 6 months of therapy.  
Severe hepatic changes and hepatic failure have been observed with bicalutamide as in  
BICALUTAMIDE 50 mg HETERO and fatal outcomes have been reported (see section 4.8).  
BICALUTAMIDE 50 mg HETERO therapy should be discontinued if changes are severe.  
A reduction in glucose tolerance has been observed in males receiving LHRH agonists and  
bicalutamide as in BICALUTAMIDE 50 mg HETERO. This may manifest as diabetes or loss of  
glycaemic control in those with pre-existing diabetes. Consideration should therefore be given to  
monitoring blood glucose in patients receiving BICALUTAMIDE 50 mg HETERO in combination with  
LHRH agonists.  
Bicalutamide has been shown to inhibit cytochrome P450 (CYP 3A4), as such caution should be  
exercised when co-administered with drugs metabolised predominantly by CYP 3A4 (see sections 4.3  
and 4.5).  
Androgen deprivation therapy may prolong the QT interval  
In patients with a history of or risk factors for QT prolongation and in patients receiving concomitant  
medicines that might prolong QT interval (see section 4.5) medical practitioners should assess the  
benefit risk ratio including the potential for Torsade de pointes prior to initiating bicalutamide.  
Clinically discontinuation of BICALUTAMIDE 50 mg HETERO can result in anti-androgen withdrawal  
syndrome in a subset of patients. This is characterised by a decline in PSA (prostate specific antigen)  
or clinical response following withdrawal of the anti-androgen component of Maximal Androgen  
Blockade (MAB). This syndrome has been well described in scientific literature although the  
pathophysiology is unknown and may reflect multiple mechanisms, but is believed to represent the  
development of agonistic activity by the medicine at the receptor level due to receptor mutations with  
advancing disease.  
M.R  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: BICALUTAMIDE 50 mg HETERO  
Dosage form and strength: Film coated tablet and 50 mg  
Antiandrogen therapy may cause morphological changes in spermatozoa. Although the effect of  
bicalutamide on sperm morphology has not been evaluated and no such changes have been reported  
for patients who received bicalutamide, patients and/or their partners should follow adequate  
contraception during and for 130 days after bicalutamide therapy.  
Potentiation of coumarin anticoagulant effects have been reported in patients receiving concomitant  
bicalutamide therapy, which may result in increased Prothrombin Time (PT) and International  
Normalised Ratio (INR). Some cases have been associated with risk of bleeding. Close monitoring of  
PT/INR is advised and anticoagulant dose adjustment should be considered (see sections 4.5 and  
4.8).  
BICALUTAMIDE 50 mg HETERO contains lactose. Patients with rare hereditary problems of  
galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this  
medicine.  
4.5 Interaction with other medicinal products and other forms of interaction  
Luteinising hormone-releasing hormone (LHRH):  
There is no evidence of any pharmacodynamic or pharmacokinetic interactions between bicalutamide  
and LHRH analogues.  
As formal interaction studies have not been undertaken, caution should be exercised when  
prescribing BICALUTAMIDE 50 mg HETERO with other medicines which may inhibit oxidation of the  
agent e.g. ketoconazole and cimetidine. In theory this could result in increased plasma concentrations  
of bicalutamide, which could lead to an increase in undesirable effects.  
[In vitro studies have shown that (R)- bicalutamide is an inhibitor of CYP 3A4, with lesser inhibitory  
effects on CYP 2C9, 2C19 and 2D6 activity.] Although clinical studies using antipyrine as a marker of  
cytochrome P450 (CYP) activity showed no evidence of an interaction potential with bicalutamide as  
in BICALUTAMIDE 50 mg HETERO, the mean midazolam exposure (AUC) was increased by up to  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: BICALUTAMIDE 50 mg HETERO  
Dosage form and strength: Film coated tablet and 50 mg  
80 %, after co-administration of bicalutamide as in BICALUTAMIDE 50 mg HETERO for 28 days. An  
increase of this magnitude for medicines with a narrow therapeutic index could be of relevance. As  
such, concomitant use of terfenadine, astemizole and cisapride is contra-indicated (see section 4.3)  
and caution should be exercised with the co-administration of BICALUTAMIDE 50 mg HETERO with  
compounds such as ciclosporin and calcium channel blockers. Dosage reduction may be required for  
these medicines particularly if there is evidence of enhanced or adverse drug effect. For ciclosporin it  
is recommended that plasma concentrations and clinical condition are closely monitored following  
initiation or cessation of therapy with BICALUTAMIDE 50 mg HETERO.  
In vitro studies have shown that bicalutamide as in BICALUTAMIDE 50 mg HETERO can displace  
the coumarin anticoagulant, warfarin, from its protein binding sites. It is therefore recommended that if  
BICALUTAMIDE 50 mg HETERO is started in patients who are already receiving coumarin  
anticoagulants, prothrombin time should be closely monitored.  
Since androgen deprivation treatment may prolong the QT interval, the concomitant use of  
bicalutamide with medicinal products known to prolong the QT interval or medicinal products able to  
include Torsade de pointes such as class 1A (e.g. quinidine, disopyramide) or class III (e.g.  
amiodarone, sotalol, dofetilide, ibutilide), antidysrhythmic medicinal products, methadone,  
moxifloxacin, etc. should be carefully evaluated (see section 4.4).  
Paediatric population  
Interaction studies have only been performed in adults.  
4.6 Fertility, pregnancy and lactation  
Pregnancy and breastfeeding  
BICALUTAMIDE 50 mg HETERO is contraindicated in females and must not be given to pregnant  
women or nursing mothers.  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: BICALUTAMIDE 50 mg HETERO  
Dosage form and strength: Film coated tablet and 50 mg  
Fertility  
Reversible impairment of male fertility has been observed in animal studies (see section 5.3). A  
period of subfertility or infertility should be assumed in man.  
4.7 Effects on ability to drive and use machines  
During treatment with bicalutamide as in BICALUTAMIDE 50 mg HETERO, somnolence has been  
reported and those patients who experience this symptom should not drive or use machines.  
4.8 Undesirable effects  
Blood and the lymphatic system disorders:  
Frequent: Anaemia  
Immune system disorders:  
Less frequent: Hypersensitivity reactions, including rash, angioedema, utricaria  
Metabolism and nutrition disorders:  
Frequent: Decreased appetite  
Psychiatric disorders:  
Frequent: Depression, decreased libido  
Nervous system disorders:  
Frequent: Dizziness, somnolence  
Cardiac disorders:  
Frequent: Myocardial infarction and cardiac failure (sometimes fatal)  
Less frequent: Conduction defects including PR and QT interval prolongation  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: BICALUTAMIDE 50 mg HETERO  
Dosage form and strength: Film coated tablet and 50 mg  
Vascular disorders:  
Frequent: Hot flushes  
Respiratory, thoracic and mediastinal disorders  
Less frequent: Interstitial lung disease (sometimes fatal), flu-like syndrome  
Gastrointestinal disorders:  
Frequent: Constipation, nausea, abdominal pain, dyspepsia, flatulence  
Hepato-biliary disorder:  
Frequent: Hepatotoxicity, jaundice (including cholestatic jaundice), hypertransaminasaemia  
Less frequent: Hepatic failure (sometimes fatal)  
Skin and subcutaneous tissue disorders:  
Frequent: Alopecia, dry skin, hirsutism/hair re-growth, rash, pruritus  
Less frequent: Photosensitivity reaction.  
Renal and urinary disorders:  
Frequent: Haematuria  
Reproductive system and breast disorder:  
Frequent: Gynaecomastia and breast tenderness, erectile dysfunction  
General disorders and administration site conditions:  
Frequent: Asthenia, oedema, chest pain  
Investigations  
Frequent: Weight increased, weight decreased  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: BICALUTAMIDE 50 mg HETERO  
Dosage form and strength: Film coated tablet and 50 mg  
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 and to the  
Holder of certificate of registration through the mail: pvg.cdma@heterogroups.com .  
Post-marketing  
Not Applicable  
4.9 Overdose  
There is no human experience of overdosage. There is no specific antidote; treatment should be  
symptomatic. Dialysis may not be helpful, since BICALUTAMIDE 50 mg HETERO is highly protein  
bound and is not removed unchanged in the urine. General supportive care, including frequent  
monitoring of vital signs, is indicated.  
5 PHARMOCOLOGICAL PROPERTIES  
5.1 Pharmacodynamic properties  
A 21.12 Hormone Inhibitors  
Mechanism of action:  
Bicalutamide is a non-steroidal anti-androgen, devoid of other endocrine activity. It binds to androgen  
receptors without activating gene expression, and thus inhibits the androgen stimulus. Regression of  
prostatic tumours results from this inhibition.  
Bicalutamide is a racemate with its anti-androgenic activity being almost exclusively in the (R) -  
enantiomer.  
M.R  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: BICALUTAMIDE 50 mg HETERO  
Dosage form and strength: Film coated tablet and 50 mg  
5.2 Pharmacokinetic properties  
Absorption  
Bicalutamide is well absorbed following oral administration. There is no evidence of any clinically  
relevant effect of food on bioavailability.  
Biotransformation  
The (S)-enantiomer is rapidly cleared relative to the (R)-enantiomer, the latter having a plasma  
elimination half-life of about 1 week.  
On daily administration of bicalutamide, the (R)-enantiomeraccumulates about 10-fold in plasma as a  
consequence of its long half-life.  
Steady state plasma concentrations of the (R)-enantiomer of approximately 9 micrograms per ml are  
observed during daily administration of 50 mg doses of bicalutamide. At steady state the  
predominantly active (R}-enantiomer accounts for 99 % of the total circulating enantiomers.  
Distribution  
Bicalutamide is highly protein bound (racemate 96%, (R)-enantiomer > 99%) and extensively  
metabolised (via oxidation and glucuronidation). Its metabolites are eliminated via the kidneys and  
bile in approximately equal proportions.  
Elimination  
The (S)-enantiomer is rapidly cleared relative to the (R)-enantiomer, the latter having a plasma  
elimination half-life of about 6 – 7 days.  
On daily administration of bicalutamide, the (R)-enantiomer accumulates about 10 fold in plasma as a  
consequence of its long half-life.  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: BICALUTAMIDE 50 mg HETERO  
Dosage form and strength: Film coated tablet and 50 mg  
Pharmacokinetics in special populations:  
The pharmacokinetics of the (R)-enantiomer are unaffected by age, renal impairment or mild to  
moderate hepatic impairment. There is evidence that the (R)-enantiomer is more slowly eliminated  
from plasma in patients with severe hepatic impairment, the (R)-enantiomer is more slowly eliminated  
from plasma.  
5.3 Preclinical safety data  
Not Applicable  
Environmental Risk Assessment:  
Not Applicable  
6. PHARMACEUTICAL PARTICULARS  
6.1 List of excipients  
Lactose monohydrate  
Povidone  
Crospovidone  
Magnesium stearate  
Opadry white Y-1-7000 (contains HPMC 2910/Hypromellose 5cP, titanium dioxide, macrogol/PEG  
400).  
6.2 Incompatibilities  
Not applicable.  
6.3 Shelf life  
24 months  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: BICALUTAMIDE 50 mg HETERO  
Dosage form and strength: Film coated tablet and 50 mg  
6.4 Special precautions for storage  
Store at or below 25 °C.  
Store in tablets in the original container until required for use.  
Keep the HDPE container tightly closed.  
Protect from light and moisture.  
Keep the HDPE container and blister strips in outer carton until required for use.  
KEEP OUT OF REACH OF CHILDREN.  
6.5 Nature and contents of container  
HDPE Bottle  
30’s or 100’s film coated tablets are packed in round, white HDPE containers closed with child  
resistant plastic caps with pulp liners.  
Blister packs  
Blister strips of plain aluminium forming foil and PVC/PVdC lidding foil, containing 10 film coated  
tablets per blister. Pack sizes: 10 film coated tablets per blister. 10 X 3 blisters packed in a box.  
HDPE bottle and blister packs are enclosed in an outer carton box.  
6.6 Special precautions for disposal and other handling  
No special requirements  
7 HOLDERS OF CERTIFICATE OF RIGISTRATION  
Hetero Drugs South Africa (Pty) Ltd,  
Jean Park Chambers  
252 Jean Avenue  
Building 6, Unit 17 & 18  
Centurion 0157  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: BICALUTAMIDE 50 mg HETERO  
Dosage form and strength: Film coated tablet and 50 mg  
8 REGISTRATION NUMBER(S)  
BICALUTAMIDE 50 mg HETERO: 49/21.12/1228  
9 DATE OF AUTHORISATION/RENEWAL OF THE AUTHORISATION  
29 JUNE 2021  
10 DATE OF REVISION OF THE TEXT  
To be advised  
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