Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: ZOSTRACOL  
Dosage form and strength: Film coated tablet and 1 mg  
APPROVED PROFESSIONAL INFORMATION FOR ZOSTRACOL  
SCHEDULING STATUS:  
S4  
1 NAME OF THE MEDICINE  
ZOSTRACOL (film coated tablets)  
2 QUALITATIVE AND QUANTITATIVE COMPOSITION  
Each film coated tablet contains 1 mg anastrozole.  
ZOSTRACOL contains sugar (lactose monohydrate)  
For the full list of excipients, see section 6.1.  
3 PHARMACEUTICAL FORM  
White colored, round shaped biconvex, film coated tablets, debossed with '1' on one side and 'H' on the other side.  
4. CLINICAL PARTICULARS  
4.1 Therapeutic indications  
-
-
-
ZOSTRACOL is indicated for the treatment of early breast cancer in postmenopausal women.  
ZOSTRACOL is indicated for the treatment of advanced breast cancer in postmenopausal women.  
Efficacy has not been demonstrated in estrogen receptor negative patients unless they have had a  
previous positive clinical response to tamoxifen.  
4.2 Posology and method of administration  
Adults including the elderly:  
One 1 mg tablet to be taken orally once daily.  
Special populations  
13 September 2023  
Initial…MU……….  
Page 1 of 12  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: ZOSTRACOL  
Dosage form and strength: Film coated tablet and 1 mg  
Renal impairment:  
No dose change is recommended in patients with mild or moderate renal impairment.  
Hepatic impairment:  
No dose change is recommended in patients with mild hepatic disease.  
Paediatric population:  
Not recommended for use in children.  
Method of administration  
ZOSTRACOL should be taken orally  
4.3 Contraindications  
•
•
•
•
•
Hypersensitivity to anastrozole or to any of the excipients of ZOSTRACOL (see section 6.1).  
Pregnancy and lactation (see section 4.6).  
Pre-menopausal women.  
Patients with severe renal impairment (creatinine clearance less than 20 ml/min) (see section 4.4).  
Patients with moderate or severe hepatic disease (see section 4.4).  
4.4 Special warnings and precautions for use  
•
Anastrozole should not be used in premenopausal women (see section 4.3). The menopause should be  
defined biochemically (luteinizing-hormone [LH], follicle stimulating hormone [FSH], and/or estradiol levels)  
in any patient where there is doubt about menopausal status.  
•
•
•
There are no data to support the use of anastrozole with luteinizing hormone-releasing hormone (LHRH)  
analogues.  
Co-administration of tamoxifen or estrogen-containing therapies with anastrozole should be avoided as this  
may diminish its pharmacological action (see sections 4.5 and 5.1).  
As ZOSTRACOL lowers circulating estrogen levels it may cause a reduction in bone mineral density with a  
13 September 2023  
Initial…MU……….  
Page 2 of 12  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: ZOSTRACOL  
Dosage form and strength: Film coated tablet and 1 mg  
consequent increased risk of fracture. This possible increased risk should be managed according to  
treatment guideline for bone healthy in postmenopausal women.  
•
There are no data to support the safe use of ZOSTRACOL in patients with moderate or severe hepatic  
impairment, or patients with severe impairment of renal function (creatinine clearance less than 20 ml/min).  
(See section 4.3)  
Lactose  
ZOSTRACOL contains lactose. Patients with the rare hereditary conditions of galactose intolerance e.g.  
•
galactosaemia, lactase deficiency, glucose-galactose malabsorption or fructose intolerance should not take  
ZOSTRACOL  
Paediatric population:  
ZOSTRACOL is not recommended for use in children and adolescents as safety and efficacy have not been  
established in this group of patients.  
4.5 Interaction with other medicines and other forms of interaction  
Antipyrine, warfarin and cimetidine clinical interaction studies indicate that the co-administration of ZOSTRACOL  
with other medicines is unlikely to result in clinically significant medicine interactions mediated by cytochrome  
P450.  
A review of the clinical trial safety database did not reveal evidence of clinically significant interaction in patients  
treated with anastrazole, as contained in ZOSTRACOL who also received other commonly prescribed medicines.  
There were no clinically significant interactions with biphosphonates.  
There is no clinical information to date on the use of ZOSTRACOL in combination with other anti-cancer  
medicines.  
Tamoxifen and/or estrogen-containing therapies should not be co-administered with ZOSTRACOL as they would  
13 September 2023  
Initial…MU……….  
Page 3 of 12  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: ZOSTRACOL  
Dosage form and strength: Film coated tablet and 1 mg  
diminish its pharmacological action.  
4.6 Fertility, pregnancy and lactation  
Pregnancy  
There is no data on the use of ZOSTRACOL in pregnant woman. Studies in animals have shown reproductive  
toxicity. ZOSTRACOL is contraindicated during pregnancy (see section 4.3).  
Breastfeeding  
There is no data on the use of ZOSTRACOL during lactation. ZOSTRACOL is contraindicated in lactating  
women (see section 4.3).  
Fertility  
The effects of ZOSTRACOL on fertility in humans have not been studies.  
4.7 Effects on ability to drive and use machines  
ZOSTRACOL may cause side effects such as asthenia and somnolence. Patients should be advised not to drive  
or operate machines until it is established that their ability to perform such activities is not affected.  
4.8 Undesirable effects  
a) Summary of the safety profile  
The most frequent adverse effects of anastrozole are gastro intestinal disturbances (including anorexia, nausea,  
and vomiting and diarrhoea) asthenia, hot flushes, dizziness, drowsiness, headache and rash. Other commonly  
reported effects include hair thinning, vaginal dryness or bleeding, myalgia, arthralgia, carpel tunnel syndrome,  
and bone pain. Insomnia, depression, peripheral oedema, lymphoedema. increased cough, pharyngitis,  
dyspnoea, back pain, and hypertension are also common.  
b) Listing of adverse reactions  
Blood and the lymphatic system disorders:  
Frequent: Lymphoedema  
13 September 2023  
Initial…MU……….  
Page 4 of 12  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: ZOSTRACOL  
Dosage form and strength: Film coated tablet and 1 mg  
Less frequent: Anaemia, leukopenia  
Metabolism and nutrition disorders  
Frequent: anorexia, hypercholesterolaemia, decreased appetite  
Psychiatric disorders  
Frequent: Insomnia, depression  
Less frequent: Somnolence, anxiety  
Nervous system disorders  
Frequent: Headache, carpal tunnel syndrome, dizziness  
Eye disorders  
Less frequent: Cataracts  
Vascular disorders  
Frequent: Hot flushes, hypertension  
Less frequent: Thromboembolism, thrombophlebitis  
Respiratory, thoracic and mediastinal disorders  
Frequent: Increased cough, pharyngitis, dyspnoea  
Less frequent: Bronchitis, rhinitis, sinusitis  
Gastrointestinal disorders  
Frequent: Nausea, diarrhoea, vomiting  
Hepato-biliary disorders  
Less frequent: Hepatitis, hypercholesterolaemia  
13 September 2023  
Initial…MU……….  
Page 5 of 12  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: ZOSTRACOL  
Dosage form and strength: Film coated tablet and 1 mg  
Skin and subcutaneous tissue disorders  
Frequent: Alopecia (hair thinning), rash, allergic reactions including angioedema, urticaria and anaphylaxis  
Less frequent: Eryhema multiformae, Stevens-Johnson syndrome  
Musculoskeletal, connective tissue and bone disorders  
Frequent: Arthralgia (joint stiffness), arthritis, myalgia, bone pain, bone fracture, osteoporosis, back pain  
Renal and urinary disorders  
Less frequent: Urinary tract infections  
Reproductive system and breast disorders  
Frequent: Vaginal dryness, vaginal haemorrhage  
Congenital and familial/genetic disorder  
Frequent: Drowsiness  
General disorders and administrative site conditions  
Frequent: Asthenia, peripheral oedema  
Investigations  
Less frequent: Hepatic enzyme abnormalities, Increase in alkaline phosphatase, alanine aminotransferase and  
aspartate aminotransferase, increase in gamma-GT and bilirubin  
c) Description of selected adverse reactions  
Events of Carpal Tunnel Syndrome have been reported in patients receiving anastrozole treatment greater  
numbers than those receiving treatment with tamoxifen. However, the majority of these events occurred in patients  
with identifiable risk factors for the development of the condition.  
13 September 2023  
Initial…MU……….  
Page 6 of 12  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: ZOSTRACOL  
Dosage form and strength: Film coated tablet and 1 mg  
Vaginal bleeding has been reported commonly, mainly in patients with advanced breast cancer during the first few  
weeks after changing from existing hormonal therapy to treatment with anastrozole. If bleeding persists, further  
evaluation should be considered.  
Post-marketing  
The following adverse reactions have been identified from post marketing experience and may be causally  
related to the use of ZOSTRACOL. Because these reactions have been reported voluntarily from a population of  
uncertain size it is not possible to accurately estimate their frequency.  
Nervous system disorder:  
Frequency unknown: somnolence  
Skin and subcutaneous tissue disorders  
Frequency unknown: anaphylactoid reaction  
Musculoskeletal, connective tissue and bone:  
Frequency unknown: trigger finger  
Reproductive system and breast disorder:  
vaginal bleeding  
Paediatric population:  
Pharmacokinetics and safety have not been studied in children.  
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  
13 September 2023  
Initial…MU……….  
Page 7 of 12  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: ZOSTRACOL  
Dosage form and strength: Film coated tablet and 1 mg  
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  
There are no reports where a patient has taken a dose excessing 60 mg. No toxicity was observed, and no clinically  
relevant adverse effects have been seen.  
A single dose of ZOSTRACOL that results in life threatening symptoms has not been established.  
Treatment:  
There is no specific antidote to overdosage and treatment must be symptomatic. In the management of an  
overdose, consideration should be given to the possibility that multiple medicines may have been taken.  
Vomiting may be induced if the patient is alert. Dialysis may be helpful because ZOSTRACOL is not highly  
protein bound. General supportive care, including frequent monitoring of vital signs and close observation of the  
patient, is indicated.  
5 PHARMOCOLOGICAL PROPERTIES  
5.1 Pharmacodynamic properties  
A 21.12 Hormone Inhibitors  
Pharmacotherapeutic group: Enzyme inibitors  
ATC code: L02B G03  
Mechanism of action:  
Anastrozole is a selective non-steroidal aromatase inhibitor. It inhibits the conversion of androstenedione to  
oestrone through the aromatase enzyme complex in peripheral tissues where oestrone is subsequently converted to  
estradiol. In postmenopausal women, anastrozole at a daily dose of 1 mg produced estradiol suppression of greater  
than 80 %.  
Anastrozole does not possess any progestogenic, androgenic or estrogenic activity.  
Anastrozole does not possess progestogenic, androgenic activity  
Anastrozole does not have any effect on cortisol or aldosterone secretion, measured before or after testing standard  
13 September 2023  
Initial…MU……….  
Page 8 of 12  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: ZOSTRACOL  
Dosage form and strength: Film coated tablet and 1 mg  
ACTH challenge testing.  
5.2 Pharmacokinetic properties:  
Absorption  
Absorption of anastrozole is rapid and maximum plasma concentrations occur after 2 hours of dosing under fasted  
conditions. Food decreases the rate but not the extent of absorption.  
Distribution  
Anastrozole is only 40 % bound to plasma proteins in the therapeutic range.  
Approximately 90 to 95 % of plasma anastrozole steady-state concentrations are attained after 7 daily doses. There  
is no evidence of time or dose-dependency of anastrozole pharmacokinetic parameters.  
Biotransformation  
Anastrozole is extensively metabolised by postmenopausal women with less than 10 % of the dose excreted in the  
urine unchanged within 72 hours of dosing. Metabolism of anastrozole occurs by N-dealkylation, hydroxylation and  
glucuronidation.  
Elimination  
Anastrozole is eliminated slowly with a plasma elimination half-life of 40 to 50 hours. The metabolites are excreted  
primarily via the urine. Triazole, a major metabolite in plasma and urine, does not inhibit aromatase.  
The apparent oral clearance of anastrozole in volunteers with mild stable hepatic cirrhosis or mild renal impairment  
was in the range has been reported  
Anastrozole pharmacokinetics are independent of age in postmenopausal woman.  
Renal or hepatic impairment  
It has been reported that the apparent clearance (CL/F) of anastrozole, following oral administration, was  
13 September 2023  
Initial…MU……….  
Page 9 of 12  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: ZOSTRACOL  
Dosage form and strength: Film coated tablet and 1 mg  
approximately 30 % lower in volunteers, with stable hepatic cirrhosis than in matched controls. However, plasma  
anastrozole concentrations in the volunteers with hepatic cirrhosis were within the range of concentrations seen in  
normal subjects in other trials. Plasma anastrozole concentrations observed during long-term efficacy trials in  
patients with hepatic impairment were within the range of plasma anastrozole concentrations seen in patients  
without hepatic impairment.  
It has been reported that the apparent clearance (CL/F) of anastrozole, following oral administration, was not altered  
in volunteers with severe renal impairment (GRF< 30 ml/min), consistent with the fact that anastrozole is eliminated  
primarily by metabolism. Plasma anastrozole concentrations observed during long-term efficacy trials in patients  
with renal impairment were within the range of plasma anastrozole concentrations see in patients without renal  
impairment. In patients with severe renal impairment, administration of anastrozole should be performed with  
caution (see section 4.2 and 4.4)  
Paediatric population  
Anastrozole pharmacokinetics have not been studied in children  
Environmental Risk Assessment:  
Anastrozole is a well-established active ingredient used in pharmaceutical preparations for human use. Given the  
anticipated pattern of use and disposal of the product, the environmental exposure of the active substance and  
metabolites are expected to be very limited. The use of Anastrozole is not considered warranting any environmental  
concerns or requiring any special product labeling.  
6 PHARMACEUTICAL PARTICULARS  
6.1 List of excipients  
Core Tablets:  
Isopropyl alcohol  
Magnesium stearate  
13 September 2023  
Initial…MU……….  
Page 10 of 12  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: ZOSTRACOL  
Dosage form and strength: Film coated tablet and 1 mg  
Povidone  
Sodium starch Glycolate  
Coated Tablet:  
Opadry white (made up of: Hypromellose (E 464), Titanium Dioxide (E 171) and Macrogol peg (E 1521)  
6.2 Incompatibilities  
Not applicable.  
6.3 Shelf life  
36 months  
6.4 Special precautions for storage  
Store at or below 25 °C. Protect from light and moisture.  
Keep the blisters in the outer carton until required for use.  
KEEP OUT OF REACH OF CHILDREN.  
6.5 Nature and contents of container  
Plain silver aluminium blister strips as a lidding foil sealed with the plain silver aluminium/clear PVC blister strips  
as a forming foil containing 10 tablets per blister packed in an outer cardboard carton.  
Pack sizes: 10, 28, 30, 56 or 60 film coated tablets per pack.  
Not all pack sizes are marketed.  
Keep the blister in outer carton until required for use.  
6.6 Special precautions for disposal and other handling  
No special requirements  
13 September 2023  
Initial…MU……….  
Page 11 of 12  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: ZOSTRACOL  
Dosage form and strength: Film coated tablet and 1 mg  
7 HOLDERS OF CERTIFICATE OF RIGISTRATION  
Hetero Drugs South Africa (Pty) Ltd  
Waterfall Corporate  
Campus, Building No.2,  
First Floor, 74 Waterfall Drive, Midrand, 2066  
Telephone number: 012 644 1220  
Fax number: 012 644 1564  
e-mail address: nokuthula.n@heterodrugs.com  
8 REGISTRATION NUMBER(S)  
47/21.12/0506  
9 DATE OF AUTHORISATION  
05 October 2021  
10 DATE OF REVISION OF THE TEXT  
13 September 2023  
13 September 2023  
Initial…MU……….  
Page 12 of 12