Kessar

Package leaflet: Information for the patient

Kessar 20 mg tablets

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

1. What Kessar is and what it is used for

Kessar contains the active substance tamoxifene, and belongs to a class of medicines called
"non-steroidal anti-estrogens". It works by blocking the activity of a hormone called
estrogen. In certain types of breast cancer, estrogen can promote the growth of
tumor cells. By blocking the effects of estrogen, Kessar inhibits or slows down the growth of
cancer cells.
Kessar is used in the treatment of breast cancer (mammary carcinoma).
It has been observed that tamoxifene also exerts estrogen-like effects on bone,
the endometrium, and blood lipids.
If you have recently undergone laboratory tests showing that your tumor cells are not
estrogen-sensitive, it is likely that you will have a reduced response to treatment with Kessar.

2. What you need to know before taking Kessar

Do not take Kessar:

• if you are allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6)
• if you are undergoing high-risk preventive therapy for breast cancer
• if you have cancer localized within an area of the breast without invasion into surrounding tissues (ductal carcinoma in situ) and you are simultaneously taking medications that thin the blood (anticoagulants), or if you have a history of deep vein thrombosis (DVT) or pulmonary artery blockage (pulmonary embolism)
• if you are pregnant or breastfeeding (see "Pregnancy and breastfeeding")
• if you are a child.

Warnings and precautions
Talk to your doctor or pharmacist before taking Kessar:

• if you are taking other medicines, particularly those that thin the blood (anticoagulants such as warfarin)
• if you are using a contraceptive method, since tamoxifen may affect the effectiveness of certain contraceptives and women taking tamoxifen must avoid pregnancy
• if you have low levels of certain blood cells (leukopenia or thrombocytopenia); your doctor will arrange periodic blood tests (full blood count, blood film, and platelet count)
• if you are taking any of the following medicines, as they may reduce the effect of tamoxifen:
  • paroxetine, fluoxetine (antidepressants)
  • bupropion (an antidepressant used to help stop smoking)
  • quinidine (used in the treatment of heart rhythm disorders)
  • cinacalcet (for the treatment of disorders of a gland called the parathyroid)
• if you have a history of hereditary angioedema, as Kessar 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, contact your doctor immediately.

During treatment with tamoxifen, it is important to undergo regular genital examinations and to immediately report to your doctor if you experience unusual vaginal bleeding, either during treatment with tamoxifen or at any time after stopping it. This is because changes in the uterus (endometrium) may occur, some of which can be serious and may include cancer.
If you are being treated with tamoxifen, you must immediately inform your doctor if you notice any of the following symptoms:

• facial numbness or weakness in the arms or legs, or speech or vision problems, which could indicate brain vessel damage (cerebral stroke)
• chest pain or difficulty breathing (dyspnea), which could be symptoms of a blockage in the pulmonary arteries (pulmonary embolism)
• abdominal pain or abnormal vaginal bleeding, which could indicate possible uterine cancer
• cough and difficulty breathing (dyspnea), which could be symptoms of lung inflammation (interstitial pneumonia). You should inform your doctor if you have a history of brain vessel damage (stroke), stroke-like events, deep vein thrombosis with or without pulmonary artery blockage (thromboembolic disorders), or uterine cancer.

If you have cancer localized within an area of the breast without invasion into surrounding tissues (ductal carcinoma in situ), discuss with your doctor the decision to start tamoxifen therapy, carefully weighing the potential risks and benefits.
If you are hospitalized, inform the medical staff that you are being treated with Kessar.
During breast reconstruction surgery (weeks or years after breast tumor removal surgery), Kessar may increase the risk of blood clots forming in the small blood vessels of the tissue flap used to shape the new breast, potentially leading to complications.
Severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in association with Kessar treatment.
Stop taking Kessar and contact your doctor immediately if you notice any of the symptoms related to these severe skin reactions described in section 4.
Treatment with Kessar must not be stopped unless instructed by your doctor.
If the cancer has spread to the bones (bone metastases), your doctor will perform blood tests during the first weeks of treatment to closely monitor your blood calcium levels, which may rise (hypercalcemia).
Taking Kessar at the recommended dose may cause heart problems, particularly in individuals who already have heart conditions or are at risk of heart rhythm disorders (QT interval prolongation). If you have heart problems or risk factors, your doctor may recommend regular electrocardiogram (ECG) monitoring and checking levels of certain salts in the blood (electrolytes).
Kessar is not indicated for use in healthy women or in conditions of benign breast disease.

Children
Kessar is contraindicated in children.

Other medicines and Kessar
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
The effects of Kessar may be affected by, or may affect, the following medicines:

• coumarin-type anticoagulants (to thin the blood), as tamoxifen may significantly increase anticoagulant activity; in such cases, your doctor will perform frequent blood tests
• cytotoxic medicines (used in chemotherapy), as concurrent use with tamoxifen may increase the risk of blood clotting (thromboembolic events)
• medicines that reduce calcium excretion by the kidneys (thiazide diuretics), as they may increase blood calcium levels (hypercalcemia)
• mitomycin (an antibiotic), as combination with tamoxifen may increase the risk of blood-related problems (hemolytic uremic syndrome, anemia, thrombocytopenia)
• medicines that inhibit certain enzymes (CYP3A4), as tamoxifen is metabolized by these enzymes
• paroxetine, fluoxetine (antidepressants)
• bupropion (antidepressant or used to help stop smoking)
• quinidine (used in the treatment of heart rhythm disorders)
• cinacalcet (for the treatment of disorders of a gland called the parathyroid)

The use of tamoxifen in combination with another breast cancer treatment medicine (aromatase inhibitor) as adjuvant therapy has not shown greater efficacy compared to tamoxifen alone.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
Kessar must not be administered during pregnancy (see "What you need to know before taking Kessar").
Do not take Kessar if you are pregnant (see section 2. Do not take Kessar); avoid pregnancy for nine months after stopping treatment. If you are sexually active, use barrier contraception (e.g., condom or diaphragm) or other non-hormonal contraceptive methods during treatment with Kessar and for nine months after stopping treatment, as there may be risks to the unborn child.
If you are premenopausal, your doctor will perform careful tests before starting treatment to rule out an existing pregnancy.

Breastfeeding
The use of Kessar during breastfeeding is not recommended, as it is unknown whether it passes into breast milk. Your doctor will decide whether to discontinue breastfeeding or Kessar treatment.

Driving and using machines
Do not drive or operate machinery if you notice that your abilities are impaired. Kessar may cause fatigue.

Kessar contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.

Other excipients
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., essentially "sodium-free".

For those engaged in sports activities
Using this medicine without therapeutic need constitutes doping and may result in a positive anti-doping test.

3. How to take Kessar

Take this medicine exactly as directed by your doctor or pharmacist.
If you have any doubts, consult your doctor or pharmacist.
The recommended daily dose is normally 20 mg of tamoxifene, administered either in two
separate doses per day or as a single daily dose (up to 40 mg of tamoxifene may be administered
per day).
Use in children
Kessar is contraindicated in children.
If you take more Kessar than you should
In case of accidental ingestion or overdose of Kessar, inform your doctor immediately or go to the nearest hospital.
If you forget to take Kessar
Do not take a double dose to make up for a forgotten tablet.
If you miss a dose due to forgetfulness, take it as soon as possible.
If you stop taking Kessar
If you have any doubts about using this medicine, consult your doctor or pharmacist.
Treatment with tamoxifene must not be stopped, even if your health condition improves, unless otherwise instructed by your doctor.

4. Possible side effects

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

• difficulty breathing;
• swelling of the face, lips, tongue and/or throat that may cause difficulty swallowing;
• swelling of the hands, feet or ankles;
• hives;
• flat, red skin lesions on the trunk shaped like targets or rings, often with central blisters, peeling of the skin, 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;
• swelling of the face, lips, tongue or throat, difficulty swallowing or breathing (angioedema). Kessar may cause or worsen symptoms of hereditary angioedema.

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 reduced blood flow to the brain (stroke);
• chest pain or shortness of breath (dyspnea), which could be symptoms 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, which could be symptoms of lung inflammation (interstitial pneumonia), characterised by fever, cough, dyspnea, increased white blood cells, a type of blood cell (neutrophilia).

During treatment with tamoxifen, as with any other medicine, the following side effects may occur according to the frequency listed below:
Very common (may affect more than 1 in 10 people)

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

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 focuses images (cataract);
• disease of the retina, the innermost layer of the eye (retinopathy);
• allergic reactions;
• increased levels of fats in the blood (triglycerides);
• leg cramps;
• muscle pain (myalgia);
• benign growths in the uterus (uterine 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 altered taste);
• itching of the external genitalia;
• changes in the endometrium, the lining of the uterus (including hyperplasia and polyps);
• hair and body hair loss (alopecia);
• vomiting;
• diarrhoea;
• constipation;
• changes in liver enzyme levels;
• fatty liver (hepatic steatosis);
• formation and dislodgement 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 the number of platelets (thrombocytopenia);
• decrease in the number of white blood cells (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) characterised by fever;
• cough, shortness of breath, increased white blood cells;
• severe liver disease (cirrhosis).

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

• decrease in the number of a type of white blood cells (neutropenia);
• severe decrease in the number of 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);
• tumour of the uterus;
• growths (polyps) in the vagina;
• 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);
• swelling 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 with formation of swellings and skin lesions (cutaneous vasculitis);
• immune system disease characterised by formation of subcutaneous swellings (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 formation of erythema, lesions, hair loss (cutaneous lupus erythematosus);
• disease caused by accumulation in the blood of certain liver proteins, porphyrins, leading to formation of blisters, lesions turning into crusts and cysts on the skin (porphyria cutanea tarda);
• skin eruption characterised by redness, swelling and/or blistering after radiotherapy (radiation recall reaction).

At the beginning of treatment, worsening of disease symptoms such as increased pain and/or enlargement of the affected area may occur. You should contact your doctor if you experience excessive nausea, vomiting and thirst. This may indicate changes in blood calcium levels (hypercalcaemia); therefore, your doctor may request blood tests.

Very rarely, cases of interstitial pneumonia have been reported.
Other side effects reported in scientific journals include: dizziness, headache, depression, confusion, easy fatigue and muscle cramps.
Results from a clinical study in women at high risk of developing breast cancer showed that women treated with tamoxifen, compared to untreated women, have an increased risk of the following adverse reactions:

• cancer of the uterus (endometrial adenocarcinoma and uterine sarcoma), sometimes fatal;
• increased blood clotting (thromboembolic events including deep vein thrombosis and pulmonary embolism), sometimes fatal;
• damage to blood vessels in the brain (cerebral stroke), sometimes fatal;
• clouding of the eye (cataract formation and cataract surgery).

Uterine fibroids, endometriosis and other endometrial changes including hyperplasia and polyps have been reported.
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
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Kessar

Do not store above 25 °C.
Keep in the original packaging to protect the medicine from light.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton 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 you no longer use. This will help protect the environment.

6. Package contents and other information

What Kessar contains

• The active substance is tamoxifene citrate. One tablet contains 30.4 mg of tamoxifene citrate, equivalent to 20 mg of tamoxifene.
• The other components are: maize starch, lactose monohydrate, polyvinylpyrrolidone, magnesium stearate, sodium carboxymethyl starch.

Description of the appearance of Kessar and contents of the pack
Kessar is available in the form of tablets.
A box contains 30 tablets of 20 mg.
Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Orion Corporation
Orionintie, 1 - FI 02200 Espoo (Finland)
Manufacturer
Orion Corporation
Orion Pharma
Orionintie, 1 - FI 02200 Espoo (Finland)
Orion Corporation
Orion Pharma
Joensuunkatu 7 - FI 24100 Salo (Finland)
Sales Licensee
Orion Pharma s.r.l. - Milan