Tamoxene

Package leaflet: Information for the patient

TAMOXENE 10 mg film-coated tablets, 20 mg film-coated tablets

Tamoxifene
Generic medicine
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What TAMOXENE is and what it is used for
2. What you need to know before taking TAMOXENE
3. How to take TAMOXENE
4. Possible side effects
5. How to store TAMOXENE
6. Contents of the pack and other information

1. What TAMOXENE is and what it is used for

TAMOXENE contains the active substance tamoxifene.
Tamoxifene belongs to a class of medicines called "anti-estrogens".
Estrogens are naturally occurring substances in the body, known as "sex hormones".
TAMOXENE works by blocking the effects of estrogens in your body.
TAMOXENE is indicated for the treatment of breast cancer.

2. What you need to know before taking TAMOXIFENE

Do not take TAMOXIFENE

• If you are allergic to tamoxifene or to any of the other ingredients of this medicine (listed in section 6).
• If you are pregnant (see 'Pregnancy and breastfeeding').
• If you are undergoing preventive therapy because you are at high risk of developing breast cancer.
• If you have a specific type of breast cancer (ductal carcinoma in situ) and require concomitant anticoagulant therapy, or if you have previously had a blood clot in a blood vessel (deep vein thrombosis or pulmonary embolism). If you are of pediatric age.
• Warnings and precautions Talk to your doctor before taking TAMOXIFENE:
• If you have low levels of white blood cells (leucopenia) or platelets (thrombocytopenia), your doctor will ask you to undergo periodic blood tests.
• If you experience unusual vaginal bleeding, either during treatment with TAMOXIFENE or at any time after stopping it, your doctor will ask you to undergo immediate examinations of the genital tract. Your doctor will also ask you to have periodic check-ups of the genital tract during treatment with TAMOXIFENE, as changes in the uterus (endometrium) may occur, some of which may be serious and could include cancer.
• If you have previously had a lack of blood flow to the brain (stroke), stroke-like events, diseases caused by formation and detachment of blood clots (thromboembolic events), or uterine cancer, as these conditions may recur during treatment with TAMOXIFENE (see section 4 Possible side effects).
• If you have a specific type of breast cancer (ductal carcinoma in situ). The decision to start tamoxifene therapy should be discussed with your doctor, weighing together the potential risks and benefits.
• If you have a history of hereditary angioedema, as TAMOXIFENE may cause or worsen symptoms of hereditary angioedema. If you experience symptoms such as swelling of the face, lips, tongue, and/or throat with difficulty swallowing or breathing, seek medical help immediately.
• If you are taking certain medicines, as they may interact with TAMOXIFENE (see Other medicines and TAMOXIFENE). TAMOXIFENE is not indicated for benign breast conditions. If you are admitted to hospital, inform the medical staff that you are being treated with TAMOXIFENE. During breast reconstruction surgery, TAMOXIFENE may increase the risk of blood clots forming in the small vessels of the tissue used to shape the new breast, which could lead to complications. Exercise particular caution with TAMOXIFENE: Severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in association with TAMOXIFENE treatment. Discontinue treatment with TAMOXIFENE and consult your doctor immediately if you notice any of the symptoms related to these severe skin reactions described in section 4.

Menstrual cessation may occur in premenopausal patients.
For athletes
Using this medicine without therapeutic need constitutes doping and may result in a positive anti-doping test.
Children and adolescents
The use of TAMOXIFENE in children is not recommended, as safety and efficacy have not been established.
Other medicines and TAMOXIFENE
Inform your doctor if you are taking, have recently taken, or might take any other medicine.
In particular, inform your doctor if you are taking:

• paroxetine, fluoxetine (examples of antidepressants);
• bupropion (an antidepressant or smoking cessation aid);
• quinidine (e.g., used in the treatment of cardiac arrhythmias);
• cinacalcet (for the treatment of parathyroid gland dysfunction);
• cytotoxic drugs (used in cancer treatment), as they may increase the risk of blood clot formation.

Your doctor will perform frequent blood tests if you are taking blood-thinning medicines known as dicoumarol-type anticoagulants (e.g., warfarin). Tamoxifene can significantly increase the activity of these medicines.
The use of tamoxifene in combination with another medicine for breast cancer treatment (an aromatase inhibitor) as adjuvant therapy has not shown greater efficacy compared to tamoxifene alone.
In some studies, reduced efficacy of tamoxifene has been reported when administered concomitantly with rifampicin and certain SSRI antidepressants (e.g., paroxetine).
Pregnancy and breastfeeding
Pregnancy
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Do not take TAMOXIFENE if you are pregnant (see section 2 Do not take TAMOXIFENE); avoid pregnancy and, if sexually active, use barrier contraception (e.g., condom or diaphragm) or other non-hormonal contraceptive methods during treatment with TAMOXIFENE and for nine months after stopping treatment, as there may be risks to the unborn child.
Consult your doctor for advice on contraception.
If you are premenopausal, your doctor will perform careful examinations before starting treatment to rule out the possibility of an existing pregnancy.
Breastfeeding
The use of TAMOXIFENE during breastfeeding is not recommended, as limited data suggest that TAMOXIFENE and its active metabolites are excreted and may accumulate over time in breast milk. Your doctor will assess whether to discontinue breastfeeding or TAMOXIFENE treatment.
Driving and using machines
Do not drive or operate machinery if you notice that your abilities are impaired. TAMOXIFENE may cause fatigue.
TAMOXIFENE contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.
TAMOXIFENE contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., essentially 'sodium-free'.

3. How to take TAMOXIFENE

Take this medicine exactly as instructed by your doctor or pharmacist. If
you have any doubts, consult your doctor or pharmacist.
The recommended dose is 20 to 40 mg in one or two daily administrations.
You must follow your doctor's instructions regarding the method and frequency of
taking the tablets.
If you take more TAMOXIFENE than you should
In case of accidental ingestion/overdose of TAMOXIFENE, inform your doctor immediately or go to the nearest hospital.
If you forget to take TAMOXIFENE
If you forget to take a dose, take it as soon as possible.
Do not take a double dose to make up for the missed tablet.
If you stop taking TAMOXIFENE
If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Stop treatment with tamoxifen and contact your doctor immediately if you experience any of the following symptoms:

• difficulty breathing;
• swelling of the face, lips, tongue or throat, difficulty swallowing or breathing (angioedema). TAMOXIFEN may cause or worsen symptoms of hereditary angioedema;
• swelling of the hands, feet or ankles;
• hives;
• flat, red rash on the trunk shaped like a target or in circular patches, often with central blisters, skin peeling, mouth, throat, nose, genital or eye ulcers. These serious skin reactions may be preceded by fever and flu-like symptoms [Stevens-Johnson syndrome, toxic epidermal necrolysis] – these side effects are rare.

Contact your doctor immediately if you experience any of the following symptoms:

• facial numbness or weakness in arms or legs, and speech or vision disturbances, which could indicate insufficient blood flow to the brain (stroke);
• chest pain or shortness of breath (dyspnea), which could be signs of a blood clot in the pulmonary artery (pulmonary embolism);
• abdominal pain or abnormal vaginal bleeding, which could indicate a possible uterine tumour;
• cough and shortness of breath (dyspnea), which could be symptoms of lung inflammation (interstitial pneumonia), characterised by symptoms such as fever, cough and dyspnea.

During treatment with tamoxifen, as with any other medicine, side effects may occur, with the following frequencies:

Very common (may affect more than 1 in 10 people)

• nausea
• fluid retention causing swelling
• vaginal bleeding
• vaginal discharge
• skin rash
• hot flushes
• fatigue
• depression

Common (may affect up to 1 in 10 people)

• decrease in the number of red blood cells (anaemia)
• clouding of the lens of the eye, which is responsible for focusing images (cataract)
• disease of the retina, the innermost layer of the eye (retinopathy)
• allergic reactions
• high levels of fats in the blood (triglycerides)
• leg cramps
• muscle pain (myalgia)
• benign uterine growths (fibroids)
• sudden onset of weakness, paralysis of arms or legs, sudden difficulty speaking, walking, holding objects, or thinking, which may be due to reduced blood flow to the brain (e.g. stroke)
• headache
• dizziness
• sensory disturbances (including numbness and taste alterations)
• itching of external genitalia
• endometrial changes (including hyperplasia and polyps)
• hair loss (alopecia)
• vomiting
• diarrhoea
• constipation
• changes in liver enzyme levels
• fatty liver (steatosis)
• formation and detachment of blood clots in blood vessels (including deep vein thrombosis, microvascular thrombosis and pulmonary embolism*).

Uncommon (may affect up to 1 in 100 people)

• decrease in platelet count (thrombocytopenia)
• decrease in white blood cell count (leucopenia)
• visual disturbances
• inflammation of the pancreas, a gland in the body (pancreatitis)
• increased calcium in the blood (hypercalcaemia) in patients with tumours that have spread to the bones
• tumour of the endometrium, the lining of the uterus (endometrial cancer)
• lung inflammation (interstitial pneumonia)
• severe liver disease (cirrhosis)

Rare (may affect up to 1 in 1,000 people)

• decrease in a type of white blood cells (neutropenia)
• severe decrease in white blood cells (agranulocytosis)
• changes in the transparent membrane covering the eye (cornea)
• disease of the optic nerve, the nerve transmitting images from the eye to the brain (optic neuropathy)
• uterine tumour
• vaginal growths (polyps)
• worsening of a tumour (tumour flare)
• endometriosis (when cells normally found only in the uterine lining are present in other parts of the body, usually in nearby organs)
• enlargement of ovarian cysts
• severe inflammation of the optic nerve, the nerve transmitting images from the eye to the brain (optic neuritis)
• liver inflammation (hepatitis)
• bile retention (cholestasis)
• liver abnormalities
• liver damage (hepatocellular)
• death of liver cells (hepatic necrosis)
• allergic reaction characterised by swelling of the face, lips and throat (angioedema)
• inflammation of blood vessels causing lumps and skin spots (cutaneous vasculitis)
• immune system disease causing subcutaneous lumps (bullous pemphigoid)
• allergic reaction characterised by skin rash (erythema multiforme).

Very rare (may affect up to 1 in 10,000 people)

• immune system disease affecting the skin with erythema, lesions and alopecia (cutaneous lupus erythematosus)
• disease caused by accumulation in the blood of certain liver proteins, porphyrins, leading to blisters, lesions turning into crusts and cysts on the skin (porphyria cutanea tarda)
• skin eruption with redness, swelling and/or blistering after radiotherapy (radiation recall reaction).

*The risk of thromboembolic events is increased when TAMOXIFEN is used in combination with cytotoxic agents.

Other side effects reported in the literature include: dizziness, headache, depression, confusion and fatigue.

Menstrual disorders (including cessation of menstrual flow) have been reported.

Results from a large 5-year study involving approximately 13,000 women at high risk of developing breast cancer showed an increased incidence of the following adverse reactions in women treated with tamoxifen compared to untreated women: uterine cancer (endometrial adenocarcinoma and uterine sarcoma), pulmonary embolism, deep vein thrombosis, stroke, cataract development and cataract surgery. Some cases of malignant uterine tumours, cerebral stroke and pulmonary embolism were fatal.

Uterine fibroids, endometriosis and other endometrial changes including hyperplasia and polyps have been reported.

Interstitial pneumonia may occur, presenting with the same symptoms as pneumonia, such as dyspnea and cough.

Reporting of side effects

If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.

Reporting side effects can help provide more information on the safety of this medicine.

5. How to store TAMOXENE

Keep this medicine out of the sight and reach of children.
Store in the original packaging to protect the medicine from light.
Do not use this medicine after the expiry date stated on the pack after EXP. The
expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What TAMOXENE contains
TAMOXENE 10 mg film-coated tablets
The active substance is: tamoxifene citrate equivalent to 10 mg of tamoxifene.
The other components are: lactose (see section 2. TAMOXENE contains lactose), maize starch,
gelatin, sodium cross-linked carboxymethylcellulose, magnesium stearate,
hydroxypropylmethylcellulose, polyethylene glycol 300, titanium dioxide.
TAMOXENE 20 mg film-coated tablets
The active substance is tamoxifene citrate equivalent to 20 mg of tamoxifene.
The other components are: lactose (see section 2. TAMOXENE contains lactose), maize starch,
gelatin, sodium cross-linked carboxymethylcellulose, magnesium stearate,
hydroxypropylmethylcellulose, polyethylene glycol 300, titanium dioxide.

Description of the appearance of TAMOXENE and pack contents
TAMOXENE 10 mg film-coated tablets are available in blisters of 30 tablets.
TAMOXENE 20 mg film-coated tablets are available in blisters of 20 tablets.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
SF Group S.r.l. – Via Tiburtina 1143 – 00156 Rome, Italy
Manufacturer
Genetic S.p.A. Contrada Canfora, 84084 Fisciano (SA), Italy
Laboratorio Italiano Biochimico Farmaceutico LISAPHARMA S.p.A.
Via Licinio, 11 - 22036 ERBA (CO), Italy