Kisqali 200 mg film-coated tablets: detailed information

Patient Information Leaflet

Introduction

Patient Information Leaflet

Kisqali 200mg film-coated tablets

ribociclib

Read the entire leaflet carefully before you start taking this medicine, because it contains important information for you.

Keep this leaflet as you may need to read it again.
If you have any questions, ask your doctor, pharmacist, or nurse.
This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you, because it may harm them.
If you experience any adverse reactions, consult your doctor, pharmacist, or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet Contents

What Kisqali is and what it is used for
What you need to know before taking Kisqali
How to take Kisqali
Possible side effects
How to store Kisqali
Package contents and additional information

1. What Kisqali is and what it is used for

What Kisqali is

Kisqali contains the active substance ribociclib, which belongs to a group of medicines called cyclin-dependent kinase (CDK) 4 and 6 inhibitors.

What Kisqali is used for

Kisqali is used in patients with a type of breast cancer called hormone receptor-positive, human epidermal growth factor receptor 2-negative (HER2-negative) breast cancer that:

is located in the breast or may have spread to the lymph nodes in the breast area, with no evidence of spread to other parts of the body, has been surgically removed, and has certain features that increase the risk of it coming back. It is used in combination with an aromatase inhibitor, which is used as hormonal therapy for cancer (early breast cancer). Women who have not yet reached menopause and men will also be treated with a medicine called a luteinizing hormone-releasing hormone (LHRH) agonist, which blocks the production of certain hormones.
is advanced or metastatic. This means that the cancer has grown beyond the breast and has spread to the lymph nodes in the breast area (locally advanced) or has spread to other parts of the body (metastatic). Kisqali is used in combination with an aromatase inhibitor or with fulvestrant, which are used as hormonal treatments for cancer. Women who have not yet reached menopause will also be treated with a luteinizing hormone-releasing hormone (LHRH) agonist, which blocks the production of certain hormones.

How Kisqali works

Kisqali works by blocking growth signals transmitted by CDK 4 and 6 proteins, thereby preventing the growth and spread of cancer cells. In early breast cancer, it may prevent the cancer from returning after surgery (treatment after surgery is called adjuvant therapy). In advanced or metastatic breast cancer, it may delay cancer progression.

If you have any questions about how Kisqali works or why it has been prescribed for you, please consult your doctor, pharmacist, or nurse.

2. What you need to know before starting Kisqali

Follow your doctor's instructions carefully. They may differ 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

Talk to 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 fever, sore throat, or mouth ulcers due to infections (signs of low white blood cell count).
If you have liver problems or have previously had any type of liver disease.
If you have or have had heart problems or irregular heart rhythms, such as an irregular heartbeat, including a condition called long QT syndrome (prolongation of the QT interval), or low levels of potassium, magnesium, calcium, or phosphorus in the blood.

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

If you develop a combination of any of the following symptoms: rash, skin redness, blistering of the lips, eyes, or mouth, skin peeling, high fever, flu-like symptoms, and swollen lymph nodes (these may be signs of a serious skin reaction).

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

Difficulty breathing, cough, and shortness of breath (these may be signs of lung or respiratory problems).

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

Monitoring during treatment with Kisqali

Before and during treatment with Kisqali, you will have periodic blood tests to check liver function, blood cell counts (white blood cells, red blood cells, and platelets), and electrolyte levels (salts in the blood including potassium, calcium, magnesium, and phosphate). Your heart activity will also be monitored before and during treatment with Kisqali using a test called an electrocardiogram (ECG). If needed, additional tests may be performed to assess kidney function during treatment with Kisqali. If necessary, your doctor may reduce or temporarily suspend your dose of Kisqali to allow recovery of the liver, kidneys, blood cells, electrolyte levels, or heart activity. Your doctor may decide to permanently discontinue treatment with Kisqali.

Children and adolescents

Kisqali must 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 need to take any other medicines, including prescription and non-prescription medicines, herbal remedies, or supplements, as these may affect the action 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 used to treat 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) – an herbal remedy 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 drug treatment).

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

Medicines used to treat symptoms of benign prostatic hyperplasia such as alfuzosin.
Tamoxifen, another medicine used to treat breast cancer.
Antiarrhythmics such as amiodarone or quinidine.
Antipsychotics such as pimozide or quetiapine.
Medicines used to improve blood lipid 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 seizures or 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 rejection of an organ transplant such as tacrolimus, sirolimus, and cyclosporine (also used to treat inflammation in rheumatoid arthritis and psoriasis).
Everolimus, used for various types of cancer and tuberous sclerosis (also used to prevent rejection of a transplanted organ).

Consult your doctor or pharmacist if you are unsure whether your medicine is one of those listed above.

Taking Kisqali with food and drink

Do not eat grapefruit or foods containing grapefruit or drink grapefruit juice during your treatment with Kisqali. This may alter how 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 plan to become pregnant, consult your doctor before using this medicine.

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

Pregnancy and women of childbearing potential

Kisqali must not be used during pregnancy as it may harm the unborn baby. If you are a woman of childbearing potential, a negative pregnancy test must be confirmed before starting treatment with Kisqali. You must use effective contraception (e.g., dual barrier methods such as condoms and diaphragm) while taking Kisqali and for at least 21 days after the last dose. Discuss effective contraceptive options with your doctor.

Breastfeeding

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

Driving and use of machines

Treatment with Kisqali may cause fatigue, dizziness, or vertigo. Therefore, caution should be exercised when driving or operating machinery during treatment with Kisqali.

Kisqali contains soya lecithin

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

3. How to take Kisqali

Follow exactly the administration instructions for this medicine as given by your doctor, pharmacist, or nurse. Your doctor, pharmacist, or nurse will inform you exactly how many tablets to take and on which days you should take them. If in doubt, consult your doctor, pharmacist, or nurse again. Do not change the dose of Kisqali or the treatment schedule without speaking to your doctor.

Do not exceed the recommended dose prescribed by your doctor.

How much Kisqali you should take

	Recommended starting dose of Kisqali	Number of tablets
Early breast cancer	400 mg once daily	2 tablets of 200 mg
Advanced or metastatic breast cancer	600 mg once daily	3 tablets of 200 mg
Note: A treatment cycle lasts 28 days. Take Kisqali once daily only on days 1 to 21 of a 28-day cycle. Do not take Kisqali on days 22 to 28 of the cycle.

The Kisqali pack includes a calendar that allows you to track 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 Kisqali tablets you should take. In certain situations (e.g., in case of liver or kidney problems), your doctor will instruct you to take a lower dose of Kisqali.

It is very important to follow your doctor's instructions. If you experience any adverse effects, your doctor may decide that you should take a lower dose, interrupt treatment with Kisqali, or stop taking 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 medication and detect any adverse effects that may occur, so you can contact your doctor promptly.

How to take Kisqali

Kisqali tablets must be swallowed whole (the tablets must not be chewed, crushed, or split 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 may 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 as long as your doctor instructs.

In early breast cancer, a maximum treatment duration of 3 years is recommended. In advanced or metastatic breast cancer, this is a long-term treatment. Your doctor will periodically monitor your condition to ensure 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 medication, contact a doctor or go to a hospital immediately. Show the Kisqali packaging. You may require medical treatment.

If you forget to take a dose of Kisqali

If you vomit after taking your 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 for your next dose and then take the dose as usual.

If you interrupt treatment with Kisqali

If you feel that your dose is too high or too low, contact your doctor. Do not interrupt treatment with Kisqali unless your doctor tells you to do so. Interrupting treatment with Kisqali may cause your cancer to worsen.

If you have any further questions about 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 everyone experiences them. Please read this section carefully. The adverse effects that could be serious are listed first (“Some adverse effects may be serious”), followed by all other possible adverse effects (“Other possible adverse effects”) listed in descending order of frequency.

Early breast cancer

Some adverse effects may be serious

Your doctor may advise you to take a lower dose, interrupt treatment with Kisqali, or discontinue treatment permanently. 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 aches, warm or painful areas of the body, 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 sores. These may be signs of low white blood cell count (very common, may affect more than 1 in 10 patients) or low lymphocyte count, which are a type of white blood cell (common, may affect 1 in 10 patients).
Abnormal blood test results indicating liver health (abnormal liver function tests). Very common (may affect more than 1 in 10 patients).
Spontaneous bleeding or bruising (signs of low platelet count). Common (may affect 1 in 10 patients).
Decreased potassium levels in the blood, which may affect heart rhythm. Common (may affect 1 in 10 patients).
Chest pain or discomfort, changes in heartbeat (fast or slow), palpitations, dizziness, fainting, near-fainting episodes, bluish discoloration of the lips, difficulty breathing, swelling (edema) in the lower limbs or skin (these may be signs of heart problems). Common (may affect up to 1 in 10 patients).
Liver problems such as fatigue, yellowing and itching of the skin, yellowing of the whites of the eyes, nausea or vomiting, loss of appetite, pain in the upper right abdomen, dark or brown-colored urine, or bleeding or bruising more easily than normal. Common (may affect up to 1 in 10 patients).
Inflammation in the lungs, which may cause dry cough, chest pain, fever, shortness of breath, and difficulty breathing (these may be signs of interstitial lung disease/pneumonitis, which can be fatal in severe cases). Common (may affect up to 1 in 10 patients).
Sore throat or mouth ulcers accompanied by a single episode of fever of at least 38.3°C or fever above 38°C lasting more than one hour and/or infection (febrile neutropenia). Uncommon (may affect up to 1 in 100 patients).

Other possible adverse effects

Other adverse effects include the following listed below. If any of these adverse effects become severe, inform your doctor, pharmacist, or nurse.

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

Sore throat, rhinitis, fever (signs of respiratory tract infection)
Painful and frequent urination (signs of urinary tract infection)
Nausea (feeling sick)
Headache
Fatigue (tiredness)
Asthenia (weakness)
Alopecia (hair loss or thinning)
Diarrhea
Constipation
Cough
Abdominal pain (in the stomach)
Pyrexia (fever)

Common (may affect up to 1 in 10 patients)

Rash
Dizziness or lightheadedness
Tiredness, pale skin (possible 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 inflamed gums)
Oro-pharyngeal pain (sore throat)
Low blood calcium levels, which may in some cases cause cramps
Decreased appetite
Abnormal blood test results for kidney function (high blood creatinine levels)

Advanced or metastatic breast cancer

Some adverse effects may be serious

Fever, sweating, or chills, cough, flu-like symptoms, weight loss, difficulty breathing, blood in phlegm, body aches, warm or painful areas of the body, 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 sores (signs of low leukocyte or lymphocyte counts, which are types of white blood cells). Very common (may affect more than 1 in 10 patients).
Abnormal blood test results indicating liver health (abnormal liver function tests). Very common (may affect more than 1 in 10 patients).
Spontaneous bleeding or bruising (signs of low platelet count). Common (may affect 1 in 10 patients)
Sore throat or mouth ulcers accompanied by a single episode of fever of at least 38.3°C or fever above 38°C lasting more than one hour and/or infection (febrile neutropenia). Common (may affect up to 1 in 10 patients).
Fatigue, yellowing and itching of the skin, yellowing of the whites of the eyes, nausea or vomiting, loss of appetite, pain in the upper right abdomen, dark or brown-colored urine, or bleeding or bruising more easily than normal (these may be signs of liver problems). Common (may affect up to 1 in 10 patients).
Decreased potassium levels in the blood, which may affect heart rhythm. Common (may affect 1 in 10 patients).
Chest pain or discomfort, changes in heartbeat (fast or slow), palpitations, dizziness, fainting, near-fainting episodes, bluish discoloration of the lips, difficulty breathing, swelling (edema) in the lower limbs or skin (these may be signs of heart problems). Common (may affect up to 1 in 10 patients).
Inflammation in the lungs, which may cause dry cough, chest pain, fever, shortness of breath, and difficulty breathing (these may be signs of interstitial lung disease/pneumonitis, which can be fatal 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, a life-threatening bloodstream infection). Uncommon (may affect up to 1 in 100 patients).
Severe skin reaction that may include a combination of the following symptoms: rash, skin redness, blisters on lips, eyes, or mouth, skin peeling, high fever, flu-like symptoms, swollen lymph nodes (toxic epidermal necrolysis [TEN]). Frequency not known (cannot be estimated from available data).

Other possible adverse effects

Other adverse effects include the following listed below. If any of these adverse effects become severe, 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 respiratory tract infection)
Frequent and painful urination (signs of 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 stomach)
Stomatitis (mouth ulcers with inflamed gums)
Dyspepsia (stomach discomfort, indigestion, heartburn)
Alopecia (hair loss or thinning)
Rash
Pruritus (itching)
Back pain
Fatigue (tiredness)
Peripheral edema (swelling in 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, an infection of the gastrointestinal tract)
Reduced blood calcium levels, which may in some cases cause cramps
Reduced blood phosphate levels
Vertigo (sensation of spinning)
Watery eyes
Dry eyes
Reduced blood potassium levels, which may cause heart rhythm disturbances
Dysgeusia (altered taste in the mouth)
Dry skin
Erythema (skin redness)
Vitiligo (loss of skin color in patches)
Oro-pharyngeal pain (sore throat)
Dry mouth
Abnormal blood test results for kidney function (high blood creatinine levels)

Rare (may affect up to 1 in 1000 patients)

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

Reporting of adverse effects

If you experience any adverse effect, consult your doctor, pharmacist, or nurse, even if it is an adverse effect not listed in this leaflet. You can also report them directly via the national reporting system detailed 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 expiry date stated on the carton and blister. The expiry date refers to the last day of the month indicated.

Store in the original packaging to protect it from moisture. This medicine does not require any special storage temperature.

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

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Kisqali

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

Tablet core: microcrystalline cellulose; crospovidone type A; low-substituted hydroxypropyl cellulose; magnesium stearate; colloidal anhydrous silica.

Film-coating material: black iron oxide (E172); red iron oxide (E172); soy lecithin (E322) (see “Kisqali contains soy lecithin” in section 2); polyvinyl alcohol (partially hydrolysed); talc; titanium dioxide (E171); xanthan gum.

What Kisqali looks like and contents of the pack

Kisqali is presented as film-coated tablets in blisters.

The film-coated tablets are light grey-violet in colour, unmarked, round, with “RIC” engraved on one side and “NVR” on the other side.

The following pack sizes are available: Packs containing 21, 42 or 63 film-coated tablets and multiple packs containing 63 (3 packs of 21), 126 (3 packs of 42) or 189 (3 packs of 63) film-coated tablets.

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

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

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

Only certain pack sizes may be marketed.

Marketing Authorisation Holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

Manufacturer

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 Nuremberg

Germany

For more information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

Belgium/Belgium/Belgium

Novartis Pharma N.V.

Tel/Tel: +32 2 246 16 11

Lithuania

SIA Novartis Baltics Lithuania Branch

Tel: +370 5 269 16 50

Text in Cyrillic characters with the word България followed by Novartis Bulgaria EOOD and the telephone number +359 2 489 98 28

Luxembourg/Luxembourg

Novartis Pharma N.V.

Tel/Tel: +32 2 246 16 11

Czech Republic

Novartis s.r.o.

Tel: +420 225 775 111

Hungary

Novartis Hungária Kft.

Tel.: +36 1 457 65 00

Denmark

Novartis Healthcare A/S

Tlf: +45 39 16 84 00

Malta

Novartis Pharma Services Inc.

Tel: +356 2122 2872

Germany

Novartis Pharma GmbH

Tel: +49 911 273 0

Netherlands

Novartis Pharma B.V.

Tel: +31 88 04 52 111

Estonia

SIA Novartis Baltics Estonia Branch

Tel: +372 66 30 810

Norway

Novartis Norge AS

Tlf: +47 23 05 20 00

Greece

Novartis (Hellas) A.E.B.E.

Tel: +30 210 281 17 12

Austria

Novartis Pharma GmbH

Tel: +43 1 86 6570

Spain

Novartis Farmacéutica, S.A.

Tel: +34 93 306 42 00

Poland

Novartis Poland Sp. z o.o.

Tel.: +48 22 375 4888

France

Novartis Pharma S.A.S.

Tél: +33 1 55 47 66 00

Portugal

Novartis Farma ‑ Pharmaceutical Products, S.A.

Tel: +351 21 000 8600

Croatia

Novartis Hrvatska d.o.o.

Tel. +385 1 6274 220

Romania

Novartis Pharma Services Romania SRL

Tel: +40 21 31299 01

Ireland

Novartis Ireland Limited

Tel: +353 1 260 12 55

Slovenia

Novartis Pharma Services Inc.

Tel: +386 1 300 75 50

Iceland

Vistor hf.

Tel: +354 535 7000

Slovakia

Novartis Slovakia s.r.o.

Tel: +421 2 5542 5439

Italy

Novartis Farma S.p.A.

Tel: +39 02 96 54 1

Finland

Novartis Finland Oy

Puh/Tel: +358 (0)10 6133 200

Cyprus

Novartis Pharma Services Inc.

Tel: +357 22 690 690

Sweden

Novartis Sverige AB

Tel: +46 8 732 32 00

Latvia

SIA Novartis Baltics

Tel: +371 67 887 070

Date of the most recent review of this leaflet

Other sources of information

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