LETROZOLE COMBIX 2.5 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the Patient

Letrozol Combix 2.5 mg film-coated tablets EFG

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Letrozol Combix and what is it used for

What is Letrozol Combix and how does it work

Letrozol Combix contains the active substance letrozole. It belongs to a group of medicines called aromatase inhibitors. It is a hormonal (or "endocrine") treatment for breast cancer. The growth of breast cancer is often stimulated by estrogens, which are female sex hormones. Letrozol Combix reduces the amount of estrogen by blocking an enzyme (aromatase) involved in estrogen production, and can therefore block the growth of breast cancers that need estrogens to grow. As a result, tumor cells grow more slowly or stop growing and/or spreading to other parts of the body.

What is Letrozol Combix used for

Letrozol Combix is used to treat breast cancer in women who have passed the menopause, i.e., the cessation of menstrual periods.

It is used to prevent breast cancer from coming back. It can be used as the first treatment before breast cancer surgery, if surgery is not immediately possible, or it can be used as the first treatment after breast cancer surgery, or after five years of treatment with tamoxifen. Letrozol Combix is also used to prevent the breast tumor from spreading to other parts of the body in patients with advanced breast cancer.

If you have any questions about how Letrozol Combix works or why you have been prescribed this medicine, ask your doctor.

2. What you need to know before you take Letrozol Combix

Follow carefully all instructions given by your doctor. They may be different from the general information contained in this leaflet.

Do not take Letrozol Combix

• if you are allergic to letrozole or any of the other ingredients of this medicine (listed in section 6),
• if you still have menstrual cycles, i.e., you have not reached menopause,
• if you are pregnant,
• if you are breast-feeding.

If any of these cases apply to you, do not take this medicine and inform your doctor.

Warnings and precautions

Consult your doctor or pharmacist before starting treatment with Letrozol Combix

• if you have severe kidney disease,
• if you have severe liver disease,
• if you have a history of osteoporosis or bone fractures (see also "Monitoring of Letrozol Combix treatment" in section 3).

If any of these cases apply to you, inform your doctor. Your doctor will take this into account during your treatment with Letrozol Combix.

Children and adolescents (under 18 years)

Children and adolescents should not use this medicine.

Elderly patients (65 years and over)

People 65 years and over can use this medicine at the same dose as for adults.

Taking Letrozol Combix with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Pregnancy, breast-feeding, and fertility

If you are pregnant or breast-feeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

• You should only take Letrozol Combix if you have passed the menopause. However, your doctor should discuss with you the use of effective contraception, as you may still become pregnant during treatment with Letrozol Combix.

• Do not take Letrozol Combix if you are pregnant or breast-feeding, as it may harm your baby.

Driving and using machines

If you feel dizzy, tired, sleepy, or unwell, do not drive or operate tools or machines until you feel better.

Letrozol Combix contains lactose. If your doctor has told you that you have an intolerance to some sugars, consult with them before taking this medicine.

Use in athletes

This medicine contains letrozole, which may produce a positive result in doping tests.

Letrozole may cause tendon inflammation or tendon damage (see section 4). If you experience any sign of pain or inflammation of the tendons, rest the affected area and contact your doctor.

3. How to take Letrozol Combix

Follow exactly the instructions for administration of this medicine given by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist again.

The recommended dose is one Letrozol Combix tablet once a day. If you take Letrozol Combix at the same time every day, it will help you remember when to take the tablet.

The tablet can be taken with or without food and should be swallowed whole with a glass of water or other liquid.

How long to take Letrozol Combix

Continue taking Letrozol Combix every day for the time your doctor tells you. You may need to take it for months or even years. If you have any doubts about how long you should take Letrozol Combix, consult your doctor.

Monitoring of Letrozol Combix treatment

You should only take this medicine under strict medical supervision. Your doctor will periodically check your condition to ensure that the treatment has the desired effect.

Letrozol Combix may cause a decrease in bone density or bone loss (osteoporosis) due to the decrease in estrogen in the body. Your doctor may decide to perform bone density measurements (a way to monitor osteoporosis) before, during, and after treatment.

If you take more Letrozol Combix than you should

If you have taken too many Letrozol Combix tablets, or if someone else has taken your tablets, contact your doctor or go to the hospital immediately. Show them the pack of tablets. You may need medical treatment. You can also call the Toxicology Information Service, phone: 915620420, indicating the medicine and the amount taken.

If you forget to take Letrozol Combix

• If it is almost time for your next dose (e.g., 2 or 3 hours), do not take the missed dose and take the next dose at the usual time.
• Otherwise, take the dose as soon as you remember, and then take the next dose as you would normally.
• Do not take a double dose to make up for missed doses.

If you stop taking Letrozol Combix

Do not stop taking Letrozol Combix unless your doctor tells you to. See also the section "How long to take Letrozol Combix".

If you have any other questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Most side effects are mild to moderate and usually disappear after a few days or weeks of treatment.

Some of these side effects, such as hot flashes, hair loss, or vaginal bleeding, may be due to the lack of estrogen.

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

Some side effects can be serious:

Rare or uncommon side effects(i.e., may affect 1 to 10 out of every 10,000 patients):

• Weakness, paralysis, or loss of sensation in any part of the body (especially arm or leg), loss of coordination, nausea, or difficulty speaking or breathing (sign of a brain disorder, e.g., stroke).
• Chest pain or sudden onset (sign of heart disorder).
• Difficulty breathing, chest pain, fainting, rapid heartbeat, bluish discoloration of the skin, or sudden pain in the arm, leg, or foot (signs of blood clots).
• Swelling and redness in a vein that is extremely soft and possibly painful to the touch.
• Severe fever, cold, or mouth ulcers due to infections (lack of white blood cells).
• Severe blurred vision.
• Tendon rupture (connective tissue that connects muscles to bones).

If you experience any of these, tell your doctor immediately.

You should also tell your doctor immediately if you experience any of the following symptoms during treatment with Letrozol Combix:

• Swelling mainly in the face and throat (signs of allergic reaction).
• Yellowing of the skin and eyes, nausea, loss of appetite, darkening of urine color (signs of hepatitis).
• Rash, redness of the skin, blisters on the lips, eyes, or mouth, skin peeling, fever (signs of skin disorder).

Some side effects are very common.These side effects may affect more than 10 out of every 100 patients.

• Hot flashes.
• High cholesterol levels (hypercholesterolemia).
• Fatigue.
• Increased sweating.
• Bone and joint pain (arthralgia).

If any of these side effects bother you seriously, talk to your doctor.

Some side effects are common.These side effects may affect 1 to 10 out of every 100 patients.

• Skin rash.
• Headache.
• Dizziness.
• General malaise.
• Gastrointestinal disorders such as nausea, vomiting, indigestion, constipation, diarrhea.
• Increased or decreased appetite.
• Muscle pain.
• Thinning or bone loss (osteoporosis), which can cause bone fractures in some cases (see also the section "Monitoring of Letrozol Combix treatment" in section 3).
• Swelling of arms, hands, feet, ankles (edema).
• Depression.
• Weight gain.
• Hair loss.
• High blood pressure (hypertension).
• Abdominal pain.
• Dry skin.
• Vaginal bleeding.
• Palpitations, rapid heartbeat.
• Joint stiffness (arthritis).
• Chest pain.

If any of these side effects bother you seriously, tell your doctor.

Some side effects are uncommon.These side effects may affect 1 to 10 out of every 1,000 patients.

• Nervous system disorders such as anxiety, nervousness, irritability, numbness, memory problems, sleepiness, insomnia.
• Sensitivity disorders, especially touch.
• Eye disorders such as blurred vision, eye irritation.
• Skin disorders such as itching (urticaria).
• Vaginal discharge or dryness.
• Breast pain.
• Fever.
• Thirst, taste disorder, dry mouth.
• Dryness of mucous membranes.
• Weight loss.
• Urinary tract infection, increased frequency of urination.
• Cough.
• Increased enzyme levels.
• Yellowing of the skin and eyes.
• High blood levels of bilirubin (a product of red blood cell breakdown).
• Tendinitis or tendon inflammation (connective tissue that connects muscles to bones).

If any of these side effects bother you seriously, tell your doctor.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Letrozol Combix

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the pack after "EXP". The expiry date is the last day of the month shown.

Do not store above 30°C. Store in the original package to protect from moisture.

Do not use any packaging that is damaged or shows signs of tampering.

Medicines should not be disposed of via wastewater or household waste. Return the packaging and any unused medicine to a pharmacy. If you have any questions, ask your pharmacist how to dispose of packaging and unused medicine. This will help protect the environment.

6. Contents of the pack and other information

Composition of Letrozol Combix

• The active substance is letrozole. Each film-coated tablet contains 2.5 mg of letrozole.
• The other ingredients (excipients) are: lactose monohydrate (lactose), microcrystalline cellulose (E460i), sodium starch glycolate (potato starch), corn starch, colloidal anhydrous silica (E551), magnesium stearate (E470b). The coating consists of hypromellose (E464), titanium dioxide (E171), and macrogol (E1521).

Appearance of Letrozol Combix and contents of the pack

• Letrozol Combix is presented as film-coated tablets. The tablets are white, round, biconvex, marked with "ZF5" on one side and smooth on the other.
• Each blister pack contains 30 film-coated tablets.

Marketing authorization holder and manufacturer

Marketing authorization holder

Laboratorios Combix, S.L.U.

C/ Badajoz 2, Edificio 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Manufacturer

Zydus France

ZAC Les Hautes Patures

Parc d'activités des Peupliers

25 Rue des Peupliers

92000 Nanterre

France

or

Centre Spécialités Pharmaceutiques

ZAC des Suzots

35 rue de la Chapelle

63450 Saint Amant Tallende

France

Date of last revision of this leaflet: August 2019

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/.