Consumer medicine information

What is in this leaflet

This leaflet answers some common questions about GENOX.

It does not contain all of the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have benefits and risks. Your doctor has weighed the risks of you taking GENOX against the benefits expected for you.

If you have any concerns about taking this medicine, talk to your doctor or pharmacist.

Keep this leaflet with your medicine. You may need to read it again.

What GENOX is used for

GENOX is used to treat breast cancer or reduce the risk of breast cancer occurring if you are at increased risk of breast cancer.

If you and your healthcare professional are considering using GENOX for reducing the risk of breast cancer occurring, your knowledge of treatment risks becomes more important because you don't currently have breast cancer. GENOX therapy may be uncommonly associated with serious side effects such as deep vein thrombosis (DVT - blood clots in veins of your leg), pulmonary embolus (blood clots in your lungs) and uterine cancer. In some women, these events were fatal. Less serious side effects such as hot flushes, vaginal discharge, menstrual irregularities and gynaecological conditions may also occur. Whether the benefits of treatment outweigh the risks depends on your age, health history, your level of breast cancer risk and on your personal judgement. GENOX therapy to reduce the risk of breast cancer may not be appropriate for all women at increased risk for breast cancer. An assessment with your healthcare professional of the potential benefits and risks prior to starting therapy for reduction in breast cancer risk is essential. You should understand that GENOX reduces, but does not eliminate, the risk of breast cancer.

GENOX contains the active ingredient tamoxifen, which works by blocking the actions of estrogen. Estrogen is a natural female sex hormone. In some types of breast cancer, estrogen can help cancer cells to grow.

Ask your doctor if you have any questions about why GENOX has been prescribed for you. Your doctor may have prescribed GENOX for another reason.

GENOX is not approved for use in children.

This medicine is available only with a doctor's prescription.

There is no evidence that GENOX is addictive.

Before you take GENOX

When you must not take it

Do not take GENOX if you are allergic to medicines containing tamoxifen or any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include:

• skin rash, itching or hives
• swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing
• wheezing or shortness of breath.

Do not take GENOX if you are pregnant or plan to become pregnant. GENOX should not be used during pregnancy. A small number of unwanted complications, such as birth defects, have been reported in the unborn baby of women who have taken this medicine. However, it has not been shown whether these were due to GENOX. If sexually active, your doctor may suggest you use a non-hormonal form of contraception while you are taking GENOX and for nine months after you have stopped treatment with it.

Do not take GENOX if you are breastfeeding. GENOX is not recommended during breastfeeding as your baby may take in GENOX from breast milk.

Do not use GENOX for reducing the risk of breast cancer occurrence if:

• you are taking medicines used to prevent blood clots such as warfarin
• you have had deep vein thrombosis (DVT - blood clots in veins of your leg) or pulmonary embolus (blood clots in your lungs).

Do not give GENOX to children. There is no experience of its use in children.

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering.

Before you start to take it

Tell your doctor if you are allergic to:

• tamoxifen, the active ingredient in GENOX
• any of the other ingredients in GENOX listed at the end of this leaflet
• other anti-estrogen medicines
• any other medicines
• any other medicines, foods, dyes or preservatives.

Tell your doctor if you have not been through menopause.

Tell your doctor if you plan to become pregnant or breastfeed. GENOX is not recommended for use in pregnancy and breastfeeding.

Tell your doctor if you have, or have had, any medical conditions, especially the following:

• a history of hereditary angioedema (as GENOX may cause or worsen symptoms of hereditary angioedema)
• liver problems
• any blood disorder or problems such as thrombocytopenia or leucopenia
• unusual or unexplained vaginal bleeding or discharge
• deep vein thrombosis (DVT - blood clots in veins of your leg) or pulmonary embolus (blood clots in your lungs).

Your doctor may want to take special care if you have any of these conditions.

If you have not told your doctor about any of the above, tell them before you start taking GENOX.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you buy without a prescription from a pharmacy, supermarket or health food shop.

Some medicines may be affected by GENOX, or may affect how well it works. These include:

• oral contraceptives ('the pill')
• hormone replacement therapy
• other medicines used to treat cancer
• medicines used to prevent blood clots such as warfarin
• rifampicin, an antibiotic
• chemotherapy
• any medicines that you buy at the chemist supermarket or health food shop.

GENOX should not be taken with aromatase inhibitors such as anastrozole, letrozole or exemestane.

These medicines may affect the way GENOX works.

Your doctor can tell you what to do if you are taking any of these medicines.

If you are not sure whether you are taking any of these medicines, check with your doctor or pharmacist. Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking GENOX.

How to take GENOX

Follow all directions given to you by your doctor and pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the pack, ask your doctor or pharmacist for help.

How much to take

The usual starting dose is 20 mg once a day. Your doctor may increase this dose to 40 mg a day, depending on your condition and how you respond to the medicine.

Patients with liver problems may need smaller doses.

GENOX is not approved for use in children.

How to take it

Swallow the tablets with a glass of water at about the same time each day. Do not chew or crush the tablets.

GENOX tablets can be taken with or without food.

How long to take it

Keep taking GENOX for as long as your doctor recommends.

If you forget to take it

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Otherwise, take the missed dose as soon as you remember, and then go back to taking your tablets as you would normally.

Do not take a double dose to make up for the dose you missed.

If you are not sure what to do, ask your doctor or pharmacist.

If you take too much (overdose)

Immediately telephone your doctor, or the Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and Emergency at the nearest hospital, if you think that you or anyone else may have taken too much GENOX. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

There have been reports of heart rhythm problems associated with an overdose of this medicine.

While you are taking GENOX

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking GENOX.

Tell all the doctors, dentists and pharmacists who are treating you that you are taking GENOX.

If you go into hospital, please let the medical staff know that you are taking GENOX.

Tell your doctor immediately if you become pregnant while taking GENOX, or within nine months of stopping treatment.

Tell your doctor immediately if you notice any unusual gynaecological symptoms, especially vaginal bleeding or discharge, even if it occurs after treatment with GENOX has stopped. Unusual bleeding or discharge from the vagina are possible side effects of GENOX but they may also be symptoms of uterine or endometrial cancer. These along with other changes to the uterus lining (endometrium) have been reported in association with the use of this medicine.

Visit your doctor regularly so they can check on your progress. You will need to have regular gynaecological check-ups while you are taking GENOX. Your doctor may also order regular blood tests to check your calcium levels, white blood cell and platelet counts.

Things you must not do

Do not breastfeed while you are taking GENOX.

Do not take GENOX to treat any other complaints unless your doctor tells you to.

Do not give your medicine to anyone else, even if they have the same condition as you.

Do not stop taking your medicine or change the dosage without checking with your doctor.

Things to be careful of

Be careful driving or operating machinery until you know how GENOX affects you. GENOX may cause dizziness, lightheadedness or fatigue in some people. If this occurs, do not drive, operate machinery or do anything else that could be dangerous.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking GENOX.

GENOX helps most people with breast cancer, but it may have unwanted side effects in some people.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. Some are associated with treatment with GENOX and some may arise from the breast cancer itself. You may need medical treatment if you get some of the side effects.

Some people, such as those who have not had menopause, may have a greater risk of getting some of these side effects.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

• depression
• hot flushes
• nausea, vomiting
• unusual vaginal discharge
• any changes in your period
• itching around the genital area
• diarrhoea or constipation
• headache, dizziness or light headedness
• hair thinning or hair loss
• leg cramps

The above list includes the milder side effects of your medicine.

Rarely an increased level of triglycerides (increased levels of fats in the blood) sometimes with pancreatitis (pain or tenderness in the upper abdomen) has been seen with GENOX.

Tell your doctor immediately if you notice any of the following:

• unusual pain or pressure around your pelvis, in your bones or anywhere in your body
• excessive thirst
• swelling of the hands, ankles and feet
• any changes in your vision
• pain and reddening around the tumour
• lumps anywhere in the body
• unusual tiredness, shortness of breath and dizziness when exercising, and looking pale
• frequent infection, fever, severe chills, sore throat or mouth ulcers
• unexplained bruising
• yellowing of the skin or eyes, dark coloured urine
• disturbances of vision

Cases of optic nerve diseases have been reported in patients receiving tamoxifen and, in a small number of cases, blindness has occurred.

If you have any unusual vaginal bleeding or other gynaecological symptoms (such as pelvic pain or pressure) when you are taking GENOX or anytime afterwards, tell your doctor. This is because a number of changes to the lining of the womb (endometrium) may occur, some of which may be serious and could include cancer.

GENOX may decrease bone density in premenopausal women. It is not known if this increases the risk of fractures. Ask your doctor for advice about ways to maintain your bone health.

GENOX may cause or worsen symptoms of hereditary angioedema.

The above list includes serious side effects which may require medical attention. Many of these side effects are rare.

Tell your doctor immediately or go to Accident and Emergency at the nearest hospital if you notice any of the following:

• rash, itching or hives
• swelling of the face, lips, tongue and/or throat, difficulty in swallowing or breathing (angioedema)
• wheezing with difficulty breathing
• sudden onset of weakness or paralysis of the arms or legs, sudden difficulty with speaking walking, difficulty in holding things or difficulty in thinking, any of which may occur because the blood supply in the blood vessels of the brain is reduced. These symptoms could be signs of a stroke.

Increased risk of blood clots and ovarian cysts (in premenopausal women) have been seen with GENOX.

The side effects listed above are serious and require urgent medical attention or hospitalisation.

Tell your doctor if you notice anything that is making you feel unwell.

This is not a complete list of all possible side effects.

Other side effects not listed above may also occur in some people.

After taking GENOX

Storage

Keep GENOX where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Keep your tablets in the pack until it is time to take them. If you take the tablets out of the pack they may not keep well.

Keep the tablets away from light.

Keep your tablets in a cool dry place where the temperature stays below 25°C.

Do not store GENOX or any other medicine in the bathroom or near a sink. Do not leave GENOX in the car or on window sills. Heat and dampness can destroy some medicines.

Disposal

If your doctor tells you to stop taking GENOX, or your tablets have passed their expiry date, ask your pharmacist what to do with any that are left over.

Product description

What it looks like

GENOX is available in 2 strengths:

• GENOX 10 - round, white tablet marked "TN" over "10" on one side and "G" on the other side.
• GENOX 20 - round, white, scored tablet marked "TN" over "20" on one side and "G" on the other side.

Each pack contains 30 or 60 tablets.

Ingredients

The active ingredient in GENOX is tamoxifen (as tamoxifen citrate).

• Each GENOX 10 tablet contains 10 mg of tamoxifen.
• Each GENOX 20 tablet contains 20 mg of tamoxifen.

The tablets also contain the following inactive ingredients:

• mannitol
• maize starch
• croscarmellose sodium
• magnesium stearate.

The tablets are gluten free.

Supplier

GENOX is supplied in Australia by:

Alphapharm Pty Ltd trading as Viatris
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.viatris.com.au
Phone: 1800 274 276

Australian registration numbers:
GENOX 10 - AUST R 40063
GENOX 20 - AUST R 40065

This leaflet was prepared in April 2023.

GENOX® is a Viatris company trade mark

GENOX_cmi\Apr23\00

Published by MIMS June 2023

1 Name of Medicine

Tamoxifen (as citrate).

2 Qualitative and Quantitative Composition

Each Genox tablet contains the active ingredient tamoxifen citrate equivalent to 10 mg or 20 mg of tamoxifen.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Genox 10.

Genox 20.

4 Clinical Particulars

4.1 Therapeutic Indications

Treatment of breast cancer.

Primary reduction of breast cancer risk.

4.2 Dose and Method of Administration

Adults.

Treatment of breast cancer.

Primary reduction of breast cancer risk.

Paediatric use.

4.3 Contraindications

Tamoxifen must not be given during pregnancy.
In premenopausal women, the possibility of pregnancy must be excluded before starting tamoxifen.
Genox should not be given to patients who have experienced hypersensitivity to tamoxifen or any of its ingredients.
When considered for primary reduction of breast cancer risk, Genox is contraindicated in women who require concomitant coumarin type anticoagulant therapy or in women with a history of deep vein thrombosis or pulmonary embolus.

4.4 Special Warnings and Precautions for Use

Endometrial changes.

Uterine cancer.

Hereditary angioedema.

McCune Albright syndrome.

Thromboembolic events.

Microvascular flap complications.

Second primary tumours.

Ocular changes.

Haematological effects.

Additional precautions relating to primary reduction of breast cancer risk.

Use in premenopausal women.

Use in the elderly.

Paediatric use.

Effects on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

When tamoxifen is used in combination with coumarin type anticoagulants, a significant increase in anticoagulant effect may occur. Where such coadministration is initiated, careful monitoring of the patient is recommended. In women receiving tamoxifen for the primary reduction of breast cancer risk, the use of coumarin type anticoagulants is contraindicated (see Section 4.3 Contraindications).
When Genox is used in combination with cytotoxic agents, there is an increased risk of thromboembolic events occurring.
The use of tamoxifen in combination with an aromatase inhibitor as adjuvant therapy has not shown improved efficacy compared with tamoxifen alone.
The known principal pathway for tamoxifen metabolism in humans is demethylation, catalysed by CYP3A4 enzymes. Pharmacokinetic interaction with the CYP3A4 inducing agent rifampicin, showing a reduction in tamoxifen plasma levels, has been reported in the literature.
Pharmacokinetic interaction between CYP2D6 inhibitors and tamoxifen has been reported in literature. This showed a reduction in plasma level of active tamoxifen metabolite, 4-hydroxy-N-desmethyltamoxifen. Reduced efficacy on tamoxifen has been reported with concomitant usage of some SSRI antidepressants (e.g. paroxetine).
For the primary reduction of breast cancer risk, there is some evidence that hormone replacement therapy may reduce the effectiveness of tamoxifen, and the safety of concomitant use of tamoxifen and hormone replacement therapy or oral contraceptives is unknown. In women with breast cancer, the use of hormone replacement therapy or oral contraceptives to manage tamoxifen side effects is a relative contraindication.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

4.7 Effects on Ability to Drive and Use Machines

Fatigue has been reported with the use of tamoxifen. Therefore, caution should be observed when driving or operating machinery while such symptoms persist.

4.8 Adverse Effects (Undesirable Effects)

The adverse reactions which have been reported are of two types:
those associated specifically with the pharmacological action of the drug, e.g. hot flushes, vaginal bleeding, vaginal discharge, pruritus vulvae; tumour pain and tumour flare;
those of a more general nature, e.g. gastrointestinal intolerance, headache, light-headedness and, occasionally, fluid retention and alopecia.
In patients treated with tamoxifen for metastatic breast cancer the most frequent adverse reactions are hot flushes, nausea and vomiting. These may occur in up to one-fourth of patients. Less frequently reported adverse reactions are vaginal bleeding, vaginal discharge, menstrual irregularities, alopecia and increased bone and tumour pain. Other adverse reactions which are seen infrequently are hypercalcaemia, peripheral oedema, pruritus vulvae, dizziness and light-headedness. Infrequent cases of endometrial, ocular and haematological adverse effects have been reported (see Section 4.4 Special Warnings and Precautions for Use).
When adverse reactions are severe, it may be possible to control them by a simple reduction of dosage (within the recommended dose range) without loss of control of the disease. If adverse reactions do not respond to this measure it may be necessary to stop the treatment.
Skin rashes (including isolated reports of erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, cutaneous vasculitis, and bullous pemphigoid) and commonly hypersensitivity reactions, including angioedema, have been reported.
Cases of exacerbation of angioedema have been reported in patients with hereditary angioedema receiving tamoxifen.
Although hypercalcaemia may occur in patients with advanced breast cancer, uncommonly patients with bony metastases have developed hypercalcaemia on initiation of therapy with tamoxifen.
Uterine fibroids, endometriosis and other endometrial changes including hyperplasia and polyps have been reported.
Cystic ovarian swellings have occasionally been observed in premenopausal women receiving tamoxifen. Vaginal polyps have rarely been observed in women receiving tamoxifen.
There is evidence of ischaemic cerebrovascular events and thromboembolic events, including deep vein thrombosis, microvascular thrombosis and pulmonary embolism, occurring commonly during tamoxifen therapy. When Genox is used in combination with cytotoxic agents, there is an increased risk of thromboembolic events occurring.
Uncommonly, cases of interstitial pneumonitis have been reported.
Leg cramps and myalgia have been reported commonly in patients receiving tamoxifen.
Tamoxifen has been associated with changes in liver enzyme levels and with a spectrum of more severe liver abnormalities which in some cases were fatal, including fatty liver, cholestasis and hepatitis, liver failure, cirrhosis and hepatocellular injury (including hepatic necrosis).
Commonly, elevation of serum triglyceride levels, in some cases with pancreatitis, may be associated with the use of tamoxifen.
Depression has been reported with frequency very common in association with the use of tamoxifen.
An increased incidence of endometrial cancer and uterine sarcoma (mostly malignant mixed Mullerian tumours) has been reported in association with tamoxifen treatment.
Cutaneous lupus erythematosus has been observed very rarely in patients receiving tamoxifen.
Porphyria cutanea tarda has been observed very rarely in patients receiving tamoxifen.
Cases of optic neuropathy and optic neuritis have been rarely reported in patients receiving tamoxifen and, in small number of cases, blindness has occurred.
Sensory disturbances (including paraesthesia and dysgeusia) have been reported commonly in patients receiving tamoxifen.
Fatigue has been reported very commonly in patients taking tamoxifen.
Radiation recall has been observed very rarely in patients receiving tamoxifen.

Primary reduction of breast cancer risk.

Women under 50 years old.

Gynaecological conditions and procedures.

Reporting suspected adverse effects.

4.9 Overdose

On theoretical grounds an overdosage would be expected to cause enhancement of the pharmacological side effects mentioned above. Observations in animals show that extreme overdosage (100 to 200 times the equivalent of the recommended daily human dose) may produce estrogenic effects.
There have been reports in the literature that tamoxifen given at several times the standard dose may be associated with prolongation of the QT interval of the ECG.
There is no specific antidote to overdosage and treatment must be supportive and symptomatic.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Clinical trials.

Primary reduction of breast cancer risk.

Concomitant use of hormone replacement therapy.

Effects of age and menopausal status.

Lobular carcinoma in situ and atypical hyperplasia.

5.2 Pharmacokinetic Properties

Absorption.

Bioavailability.

Distribution.

Protein binding.

Metabolism.

Excretion.

Half-life.

Clinical implications of pharmacokinetic data.

5.3 Preclinical Safety Data

Genotoxicity.

Carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

The tablets also contain the following inactive ingredients: mannitol, maize starch, croscarmellose sodium and magnesium stearate. The tablets are gluten free.

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

Store below 25°C. Protect from light.

6.5 Nature and Contents of Container

Container type: PVC/Al blister in the packs of 30 and 60 tablets.
Some strengths, pack sizes and/or pack types may not be marketed.

Australian register of therapeutical goods (ARTG).

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Tamoxifen citrate is a white or almost white, crystalline powder, slightly soluble in water, soluble in methanol, slightly soluble in acetone.

Chemical structure.

CAS number.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes