KISQALI 200 mg FILM-COATED TABLETS

2. What you need to know before you take Kisqali

Follow your doctor's instructions carefully. They may be different from the general information in this leaflet.

Do not take Kisqali

• if you are allergic to ribociclib, peanuts, soy, or any of the other ingredients of this medicine (listed in section 6).

If you think you may be allergic, consult your doctor.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting Kisqali.

If you are in any of the following situations before taking Kisqali, consult your doctor or pharmacist:

• If you have a fever, sore throat, or mouth sores due to infections (signs of a low white blood cell count).
• If you have any liver problems or have had liver disease in the past.
• If you have or have had heart problems or heart rhythm disorders, such as an irregular heartbeat, including a condition called QT prolongation or low levels of potassium, magnesium, calcium, or phosphorus in the blood.

If you are in any of the following situations during treatment with Kisqali, inform your doctor or pharmacist:

• If you experience a combination of any of the following symptoms: rash, skin redness, blisters on the lips, eyes, or mouth, skin peeling, high fever, flu-like symptoms, and swollen lymph nodes (may be signs of a severe skin reaction).

In case of a severe skin reaction, your doctor will instruct you to stop treatment with Kisqali immediately.

• Breathing problems, cough, and difficulty breathing (may be signs of lung or respiratory problems).

If necessary, your doctor may interrupt or reduce your dose of Kisqali or decide to stop treatment with Kisqali permanently.

Checks during treatment with Kisqali

Before and during treatment with Kisqali, you will have regular blood tests to check liver function and the number of blood cells (white blood cells, red blood cells, and platelets) and electrolytes (salts in the blood, including potassium, calcium, magnesium, and phosphate) in your body. You will also have your heart activity checked before and during treatment with Kisqali with a test called an electrocardiogram (ECG). If necessary, you will have additional tests to evaluate kidney function during treatment with Kisqali. If necessary, your doctor may reduce the dose of Kisqali or temporarily stop it to allow the liver, kidney, blood cells, electrolyte levels, or heart activity to recover. Your doctor may decide to stop treatment with Kisqali permanently.

Children and adolescents

Kisqali should not be used in children and adolescents under 18 years of age.

Other medicines and Kisqali

Before taking Kisqali, tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those with a prescription and without a prescription, herbal medicines, or supplements, as they may influence the effect of Kisqali. Always inform your doctor if you have been prescribed a new medicine after starting treatment with Kisqali.

This includes in particular:

• Tamoxifen, another medicine for the treatment of breast cancer.
• Some medicines used to treat fungal infections, such as ketoconazole, itraconazole, voriconazole, or posaconazole.
• Some medicines used to treat HIV/AIDS, such as ritonavir, saquinavir, indinavir, lopinavir, nelfinavir, telaprevir, and efavirenz.
• Some medicines used to treat seizures or fits (antiepileptics) such as carbamazepine and phenytoin.
• St. John's Wort (also known as Hypericum perforatum) - a herbal medicine used to treat depression and other conditions.
• Some medicines used to treat heart rhythm problems or high blood pressure, such as amiodarone, disopyramide, procainamide, quinidine, sotalol, and verapamil.
• Antimalarial medicines such as chloroquine.
• Antibiotics such as clarithromycin, telithromycin, moxifloxacin, rifampicin, ciprofloxacin, levofloxacin, and azithromycin.
• Some medicines used for sedation or anesthesia, such as midazolam.
• Some medicines used as antipsychotics, such as haloperidol.
• Medicines used to treat angina, such as bepridil.
• Methadone, used to treat pain or opioid addiction.
• Medicines such as intravenous ondansetron, used to prevent nausea and vomiting caused by chemotherapy (cancer treatment).

Kisqali may increase or decrease the levels of other medicines in the blood. This includes in particular:

• Medicines used to treat symptoms of benign prostatic hyperplasia, such as alfuzosin.
• Tamoxifen, another medicine for the treatment of breast cancer.
• Antiarrhythmics, such as amiodarone or quinidine.
• Antipsychotics, such as pimozide or quetiapine.
• Medicines used to improve blood fat levels, such as simvastatin or lovastatin, pitavastatin, pravastatin, or rosuvastatin.
• Medicines used to treat high blood sugar levels (e.g., diabetes), such as metformin.
• Medicines used to treat heart conditions, such as digoxin.
• Medicines used to treat pulmonary arterial hypertension and erectile dysfunction, such as sildenafil.
• Medicines used to treat low blood pressure or migraine, such as ergotamine or dihydroergotamine.
• Some medicines used to treat epileptic fits or used for sedation or anesthesia, such as midazolam.
• Medicines used to treat sleep disorders, such as triazolam.
• Painkillers, such as alfentanil and fentanyl.
• Medicines used to treat gastrointestinal disorders, such as cisapride.
• Medicines used to prevent organ transplant rejection, such as tacrolimus, sirolimus, and cyclosporin (also used to treat inflammation in rheumatoid arthritis and psoriasis).
• Everolimus, used for various types of cancer and tuberous sclerosis (also used to prevent organ transplant rejection).

Ask your doctor or pharmacist if you are not sure if your medicine is one of those listed above.

Taking Kisqali with food and drink

Do not eat grapefruit or foods that contain grapefruit or drink grapefruit juiceduring your treatment with Kisqali. It may change the way Kisqali is processed in your body and may increase the amount of Kisqali in the blood, making it less effective.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine.

Your doctor will discuss with you the possible risks of taking Kisqali during pregnancy.

Pregnancy and women of childbearing age

Kisqali should not be used during pregnancy as it may harm the fetus. If you are a woman of childbearing age, you must have a negative pregnancy test before starting treatment with Kisqali. You must use effective contraception (e.g., double-barrier contraception such as condoms and diaphragm) while taking Kisqali and for at least 21 days after the last dose. Ask your doctor about effective contraception options.

Breastfeeding

You must not breastfeed while taking Kisqali and for at least 21 days after the last dose.

Driving and using machines

Treatment with Kisqali may cause fatigue, dizziness, or a feeling of spinning. Therefore, you should be careful when driving or using machines during treatment with Kisqali.

Kisqali contains soy lecithin

If you are allergic to peanuts or soy, do not take this medicine.

3. How to take Kisqali

Follow the instructions for administration of this medicine exactly as told by your doctor, pharmacist, or nurse. Your doctor, pharmacist, or nurse will inform you exactly how many tablets to take and which days to take them. If you are unsure, ask your doctor, pharmacist, or nurse again. Do not change the dose of Kisqali or the treatment schedule without talking to your doctor.

Do not exceed the recommended dose prescribed by your doctor.

How much Kisqali to take

• The Kisqali pack includes a calendar that allows you to keep track of your daily dose of Kisqali by marking a circle for each tablet you take during the 28-day cycle.

• Your doctor will inform you exactly how many tablets of Kisqali to take. In certain situations (e.g., in case of liver or kidney problems), your doctor may instruct you to take a lower dose of Kisqali.

It is very important to follow your doctor's instructions. If you experience any side effects, your doctor may decide to reduce the dose, interrupt treatment with Kisqali, or stop it permanently.

When to take Kisqali

Take Kisqali once daily at the same time each day, preferably in the morning. This will help you remember to take your medicine and to detect any side effects that may occur so that you can contact your doctor quickly.

How to take Kisqali

Kisqali tablets should be swallowed whole (tablets should not be chewed, crushed, or broken before swallowing). Do not take a tablet that is broken, cracked, or damaged.

Taking Kisqali with food and drink

You should take Kisqali once daily at the same time each day, preferably in the morning. You can take it with or without food.

How long to take Kisqali

Take Kisqali once daily on days 1 to 21 of a 28-day cycle. Continue treatment with Kisqali for the time period indicated by your doctor.

In early breast cancer, the maximum recommended treatment duration is 3 years. In advanced or metastatic breast cancer, this is a long-term treatment. Your doctor will periodically check your condition to ensure that the treatment is having the desired effect.

If you take more Kisqali than you should

If you take too many tablets, or if someone else takes your medicine, contact a doctor or go to a hospital immediately. Show the Kisqali pack. You may need medical treatment.

If you forget to take a dose of Kisqali

If you vomit after taking the dose or if you forget to take a dose, do not take the missed dose that day. Take the next dose the following day at the prescribed time.

Do not take a double dose to make up for missed doses. Instead, wait until the time you should take the next dose and then take the dose as usual.

If you stop taking Kisqali

If you think the dose you are taking is too high or too low, contact your doctor. Do not stop taking Kisqali unless your doctor tells you to. If you stop taking Kisqali, it may cause your cancer to worsen.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them. Read this section carefully. The adverse effects that could be serious are presented first (“Some adverse effects can be serious”), and then all the other adverse effects (“Other possible adverse effects”) are described in descending order of frequency.

Breast Cancer

Some adverse effects may be serious

Your doctor may instruct you to take a lower dose, interrupt treatment with Kisqali, or permanently discontinue treatment. Inform your doctor immediately if you experience any of the following symptoms during treatment with Kisqali:

• Fever, sweating, or chills, cough, flu-like symptoms, weight loss, difficulty breathing, blood in phlegm, body pain, hot or painful body parts, diarrhea, or stomach pain, or feeling very tired (signs or symptoms of infections). Very common (may affect more than 1 in 10 patients).
• Fever, chills, weakness, and frequent infections with symptoms such as sore throat or mouth ulcers. These may be signs of a low white blood cell count (very common, may affect more than 1 in 10 patients) or a low lymphocyte count, which is a type of white blood cell (common, may affect 1 in 10 patients).
• Abnormal blood test results that provide information about liver health (abnormal liver function tests). Very common (may affect more than 1 in 10 patients).
• Spontaneous bleeding or bruising (signs of a low platelet count). Common (may affect 1 in 10 patients).
• Decreased potassium levels in the blood, which can alter the heart rhythm. Common (may affect 1 in 10 patients).
• Chest pain or discomfort, changes in heart rate (fast or slow), palpitations, dizziness, fainting, syncope, blue discoloration of the lips, difficulty breathing, swelling (edema) of the lower extremities or skin (these may be signs of heart problems). Common (may affect up to 1 in 10 patients).
• Lung inflammation, which can cause dry cough, chest pain, fever, shortness of breath, and difficulty breathing (these may be signs of interstitial lung disease/pneumonitis, which can be life-threatening in severe cases). Common (may affect up to 1 in 10 patients).

• Sore throat or mouth ulcers with a single episode of fever of at least 38.3°C or fever above 38°C for more than an hour and/or with infection (febrile neutropenia). Uncommon (may affect up to 1 in 100 patients).

Other Possible Adverse Effects

Other adverse effects include the following, which are detailed below. If these adverse effects become serious, inform your doctor, pharmacist, or nurse.

Very Common(may affect more than 1 in 10 patients)

• Sore throat, rhinitis, fever (signs of a respiratory tract infection)
• Painful or frequent urination (signs of a urinary tract infection)

• Nausea (feeling sick)
• Headache
• Fatigue (tiredness)
• Asthenia (weakness)
• Alopecia (hair loss or hair weakening)
• Diarrhea
• Constipation
• Cough
• Abdominal pain (in the abdomen)

• Pyrexia (fever)

Common(may affect up to 1 in 10 patients)

• Rash
• Dizziness or lightheadedness
• Tiredness, pale skin (potential sign of low red blood cell count, anemia)
• Vomiting
• Pruritus (itching)
• Peripheral edema (swelling of hands, ankles, or feet)
• Dyspnea (shortness of breath, difficulty breathing)
• Stomatitis (mouth ulcers with gum inflammation)
• Oropharyngeal pain (sore throat)
• Low calcium levels in the blood, which can cause cramps
• Decreased appetite
• Abnormal kidney function test results (high creatinine levels in the blood)

Advanced or Metastatic Breast Cancer

Some Adverse Effects Can Be Serious

Your doctor may instruct you to take a lower dose, interrupt treatment with Kisqali, or permanently discontinue treatment. Inform your doctor immediately if you experience any of the following symptoms during treatment with Kisqali:

• Fever, sweating, or chills, cough, flu-like symptoms, weight loss, difficulty breathing, blood in phlegm, body pain, hot or painful body parts, diarrhea, or stomach pain, or feeling very tired (signs or symptoms of infections). Very common (may affect 1 in 10 patients)
• Fever, chills, weakness, and frequent infections with symptoms such as sore throat or mouth ulcers (signs of a low white blood cell count or low lymphocyte count, which is a type of white blood cell). Very common (may affect more than 1 in 10 patients).
• Abnormal blood test results that provide information about liver health (abnormal liver function tests). Very common (may affect more than 1 in 10 patients).
• Spontaneous bleeding or bruising (signs of a low platelet count). Common (may affect 1 in 10 patients)
• Sore throat or mouth ulcers with a single episode of fever of at least 38.3°C or fever above 38°C for more than an hour and/or with infection (febrile neutropenia). Common (may affect up to 1 in 10 patients).
• Tiredness, yellow skin with itching, or yellowish color of the white part of the eyes, nausea or vomiting, loss of appetite, pain in the upper right part of the abdomen (abdomen), dark or brown urine, or if you experience bleeding or bruising more easily than usual (these may be signs of a liver problem). Common (may affect up to 1 in 10 patients).
• Decreased potassium levels in the blood, which can alter the heart rhythm. Common (may affect 1 in 10 patients).
• Chest pain or discomfort, changes in heart rate (fast or slow), palpitations, dizziness, fainting, syncope, blue discoloration of the lips, difficulty breathing, swelling (edema) of the lower extremities or skin (these may be signs of heart problems). Common (may affect up to 1 in 10 patients).
• Lung inflammation, which can cause dry cough, chest pain, fever, shortness of breath, and difficulty breathing (these may be signs of interstitial lung disease/pneumonitis, which can be life-threatening in severe cases). Common (may affect up to 1 in 10 patients).
• Severe infection with increased heart rate, difficulty breathing or rapid breathing, fever, and chills (these may be signs of sepsis, which is a life-threatening infection in the bloodstream). Uncommon (may affect up to 1 in 100 patients).
• Severe skin reaction that could include a combination of some of the following symptoms: rash, skin redness, blisters on the lips, eyes, or mouth, skin peeling, high fever, flu-like symptoms, enlarged lymph nodes (toxic epidermal necrolysis [TEN]). Frequency not known (cannot be estimated from the available data).

Other Possible Adverse Effects

Other adverse effects include the following, which are detailed below. If these adverse effects become serious, inform your doctor, pharmacist, or nurse.

Very Common(may affect more than 1 in 10 patients)

• Tiredness, pale skin (possible sign of low red blood cell count, anemia)
• Sore throat, rhinitis, fever (signs of a respiratory tract infection)
• Frequent or painful urination (signs of a urinary tract infection)

• Decreased appetite
• Headache
• Dizziness or lightheadedness
• Dyspnea (shortness of breath, difficulty breathing)
• Cough
• Nausea (feeling sick)
• Diarrhea
• Vomiting
• Constipation
• Abdominal pain (in the abdomen)
• Stomatitis (mouth ulcers with gum inflammation)
• Dyspepsia (stomach discomfort, indigestion, heartburn)
• Alopecia (hair loss or hair weakening)
• Rash

• Pruritus (itching)
• Back pain
• Fatigue (tiredness)
• Peripheral edema (swelling of hands, ankles, or feet)
• Pyrexia (fever)
• Asthenia (weakness)

Common(may affect up to 1 in 10 patients)

• Abdominal pain, nausea, vomiting, and diarrhea (signs of gastroenteritis, which is an infection of the gastrointestinal tract)
• Reduced calcium levels in the blood, which can cause cramps
• Reduced phosphate levels in the blood
• Vertigo (feeling of spinning)
• Tearing
• Dry eyes
• Reduced potassium levels in the blood, which can cause heart rhythm alterations
• Dysgeusia (strange taste in the mouth)
• Dry skin
• Erythema (skin redness)
• Vitiligo (loss of skin color in patches)
• Oropharyngeal pain (sore throat)
• Dry mouth
• Abnormal kidney function test results (high creatinine levels in the blood)

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

A skin reaction that causes red spots or patches on the skin, which may resemble a target or a "bull's eye" with a dark red center surrounded by lighter red rings (erythema multiforme)

Reporting of Adverse Effects

If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Kisqali

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

Do not use this medicine after the expiration date stated on the carton and blister. The expiration date is the last day of the month indicated.

Pharmacy: Store in a refrigerator (between 2°C and 8°C) for up to 10 months.

Patient: Store below 25°C for up to 2 months. Store in the original package.

Do not take this medicine if you notice any damage to the packaging or if it shows signs of tampering.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Kisqali

• The active ingredient is ribociclib. Each film-coated tablet contains ribociclib succinate equivalent to 200 mg of ribociclib.
• The other ingredients are:

Core of the tablet: microcrystalline cellulose; crospovidone type A; low-substituted hydroxypropyl cellulose; magnesium stearate; anhydrous colloidal silica.

Coating material: black iron oxide (E172); red iron oxide (E172); soybean lecithin (E322) (see "Kisqali contains soybean lecithin" in section 2); partially hydrolyzed polyvinyl alcohol; talc; titanium dioxide (E171); xanthan gum.

Appearance of Kisqali and Package Contents

Kisqali is presented as film-coated tablets in blisters.

The film-coated tablets are light gray-violet, without a score line, round, and engraved with "RIC" on one side and "NVR" on the other side.

The following package sizes are available: packages containing 21, 42, or 63 film-coated tablets and multipacks containing 63 (3 packages of 21), 126 (3 packages of 42), or 189 (3 packages of 63) film-coated tablets.

Kisqali packages containing 63 tablets, intended for patients taking the daily dose of 600 mg ribociclib (3 tablets once daily).

Kisqali packages containing 42 tablets, intended for patients taking the daily dose of 400 mg ribociclib (2 tablets once daily).

Kisqali packages containing 21 tablets, intended for patients taking the lowest daily dose of 200 mg ribociclib (1 tablet once daily).

Not all package sizes may be marketed.

Marketing Authorization Holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

Manufacturer

Novartis Pharma GmbH

Roonstrasse 25

90429 Nuremberg

Germany

Lek Pharmaceuticals d.d.

Verovškova Ulica 57

1526 Ljubljana

Slovenia

Novartis Pharmaceutical Manufacturing LLC

Verovškova Ulica 57

1000 Ljubljana

Slovenia

Novartis Pharma GmbH

Sophie-Germain-Strasse 10

90443 Nürnberg

Germany

You can obtain more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet

Other Sources of Information

Detailed information about this medicine is available on the European Medicines Agency website: https://www.ema.europa.eu