TIBSOVO 250 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the Patient

Tibsovo 250 mg film-coated tablets

ivosidenib

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. The last section of section 4 will include information on how to report side effects.

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

1. What is Tibsovo and what is it used for

What is Tibsovo

Tibsovo contains the active substance ivosidenib. It is a medicine used to treat certain types of cancer that include a mutated (altered) gene that produces a protein known as IDH1, which plays an important role in energy production for cells. When the IDH1 enzyme is mutated, metabolic changes in the cell can lead to cancer development.

Tibsovo blocks the mutated form of the IDH1 protein and helps slow down or stop cancer growth.

What is Tibsovo used for

Tibsovo is used to treat adults with:

• acute myeloid leukemia (AML). When used in patients with AML, Tibsovo is administered in combination with another cancer medicine called "azacitidine".
• bile duct cancer (also known as "cholangiocarcinoma"). Tibsovo is used as monotherapy to treat patients whose bile duct cancer has spread to other parts of the body and who have received at least one previous treatment.

Tibsovo is only used in patients with AML or bile duct cancer that are related to a change (mutation) in the IDH1 protein.

2. What you need to know before you take Tibsovo

Your doctor will perform a test to check if you have a mutation in the IDH1 protein before deciding if this medicine is the right treatment for you.

Do not take Tibsovo

• if you are allergicto ivosidenibor to any of the other ingredientsof this medicine (listed in section 6);
• if you are already taking medicines such as dabigatran (a medicine used to prevent blood clots), St. John's Wort (a herbal remedy used for depression and anxiety), rifampicin (a medicine used to treat bacterial infections) or certain medicines used to treat epilepsy (e.g. carbamazepine, phenobarbital, phenytoin).
• if you have a congenital heart problem called "congenital long QTc syndrome".
• if you have a family history of sudden death or abnormal or irregular heartbeats in the lower chambers of the heart.
• if you have a serious heart conduction abnormality that affects your rhythm, called "QTc interval prolongation".

Do not take Tibsovo if any of the above applies to you. If you are not sure, talk to your doctor or pharmacist.

Warnings and precautions

QTc interval prolongation:

Tibsovo may cause a serious condition known as QTc interval prolongation, which can cause irregular heartbeats and potentially life-threatening arrhythmias (abnormal electrical activity of the heart that affects your rhythm). Your doctor should check your heart's electrical conduction system before and during treatment with Tibsovo (see 'Regular checks').

Seek urgent medical attentionif you experience dizziness, fainting, palpitations, or syncope (see also section 4) after taking Tibsovo.

During treatment, inform your doctors that you are taking Tibsovo before starting to take any new medicine, as it may increase the risk of an abnormal heart rhythm.

If you experience any of the serious side effects mentioned above, your doctor may give you other medicines to treat them and may tell you to stop treatment with Tibsovo for a while or completely.

Talk to your doctor before takingTibsovo if:

• you have heart problemsor have abnormal levels of electrolytes(such as sodium, potassium, calcium, or magnesium);
• you are taking certain medicines that may affect the heart(e.g. those used to prevent arrhythmia, called anti-arrhythmics, some antibiotics, some antifungals, and those used to prevent nausea and vomiting, see "Other medicines and Tibsovo");
• you have kidney problems;
• you have liver problems.

Regular checks

Your doctor will closely monitor you before and during treatment with Tibsovo. You will need to have regular electrocardiograms (ECG; a record of your heart's electrical activity) to check your heart rhythm. You will have an ECG before starting treatment with Tibsovo, once a week during the first three weeks of treatment, and then monthly. Additional ECGs may be performed as directed by your doctor. If you start taking certain medicines that may affect your heart, you will have an ECG before starting and during treatment with the new medicine, as necessary.

You will also have blood tests before starting treatment with Tibsovo and regularly thereafter.

If necessary, your doctor may reduce your dose of Tibsovo, temporarily interrupt it, or stop it completely.

Children and adolescents

Do notgive this medicine to children and adolescents under 18 years of age because there is no information on its use in this age group.

Other medicines and Tibsovo

Tell your doctor if you are taking, have recently taken, or might take any other medicines. This is because they may reduce the effectiveness of Tibsovo or increase the risk of side effects, or Tibsovo may affect how these other medicines work.

In particular, tell your doctorif you are taking any of the following medicines so that they can decide if it is necessary to change your treatment:

• antibioticsused for bacterial infections (e.g. erythromycin, clarithromycin, benzylpenicillin, ciprofloxacin, levofloxacin);
• warfarin(used to prevent blood clots);
• medicines used for fungal infections(e.g. itraconazole, ketoconazole, fluconazole, isavuconazole, posaconazole, voriconazole);
• medicines that affect heartbeatsknown as anti-arrhythmics (e.g. diltiazem, verapamil, quinidine);
• medicines used to prevent nausea and vomiting,known as antiemetics (e.g. aprepitant, ondansetron, tropisetron, granisetron);
• medicines used after organ transplantsknown as immunosuppressants (e.g. cyclosporin, everolimus, sirolimus, tacrolimus);
• medicines used for HIV(e.g. raltegravir, ritonavir);
• alfentanil(used for anesthesia in surgery);
• fentanyl(used for severe pain);
• pimozide(used for schizophrenia);
• medicines used for cancer(e.g. cyclophosphamide, ifosfamide, paclitaxel);
• methadone(used for morphine or heroin addiction, or for severe pain);
• medicines used for type 2 diabetes(e.g. pioglitazone, repaglinide);
• omeprazole(used for stomach ulcers and acid reflux);
• furosemide(used for fluid accumulation known as edema);
• medicines used for high cholesterolknown as statins (e.g. atorvastatin, pravastatin, rosuvastatin).
• lamotrigine(used for epilepsy).

Taking Tibsovo with food and drinks

• Do nottake grapefruit or grapefruit juice during treatment with Tibsovo as it may affect how this medicine works.

Pregnancy, breastfeeding, and fertility

Tibsovo is not recommended during pregnancy, as it may harm the fetus. Women of childbearing age should have a pregnancy test before starting treatment with Tibsovo and should avoid becoming pregnant during treatment.

If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor before taking this medicine. Contact your doctor or pharmacist immediately if you become pregnant while taking Tibsovo.

Contraception

Tibsovo should not be used during pregnancy as it may harm the fetus. Women who can become pregnant or men with partners who can become pregnant must use effective contraceptive methods to avoid pregnancy during treatment with Tibsovo and for at least 1 month after the last dose.

Tibsovo may prevent hormonal contraceptives from working properly. If you or your partner use hormonal contraceptives (e.g. birth control pills, or contraceptive patches or implants), you must also use a barrier method(e.g. condoms or a diaphragm) to prevent pregnancy. Consult your doctor or pharmacist about the appropriate contraceptive method for you.

Breastfeeding

It is not known if Tibsovo passes into breast milk. Do notbreastfeed your baby during treatment with Tibsovo and for at least 1 month after the last dose.

Fertility

It is not known if Tibsovo affects fertility. If you are concerned about your fertility while taking Tibsovo, talk to your doctor.

Driving and using machines

This medicine has a minor influence on your ability to drive or use tools or machines. If you feel unwell after taking Tibsovo, do not drive or use tools or machines until you feel better.

Tibsovo contains lactose and sodium

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

This medicine contains less than 1 mmol of sodium (23 mg) per tablet; this is essentially "sodium-free".

3. How to take Tibsovo

Follow the instructions for administration of this medicine exactly as directed by your doctor.

If you are unsure, consult your doctor or pharmacist again.

The recommended dose is 2 tablets(500 mg of ivosidenib) to be taken once a day, approximately at the same time each day.

Your doctor may instruct you to take 1 tablet(250 mg of ivosidenib) if you are taking other medicinesor to help you tolerate some possible side effects better.

• Take the tablets without food. Do not eat anything for 2 hours beforeand 1 hour after

taking the tablets.

• Swallow the tablets whole with water.
• Do not swallowthe desiccantthat is in the bottle. The desiccant helps protect the tablets from moisture (see section 5 and section 6).
• If you vomit after taking your usual dose, do not takeextra tablets. Take your next dose as usual the next day.

If you take more Tibsovo than you should

If you accidentally take more tablets than your doctor has prescribed, seek urgent medical attentionand bring the medicine bottle with you.

If you forget to take Tibsovo

If you forget a dose or do not take it at the usual time, take the tablets as soon as possible, unless the next dose is due within the next 12 hours. Do not taketwo doses within 12 hours. Take the next dose as usual the next day.

How long to take Tibsovo

You should keep taking this medicine until your doctor tells you to stop. Do not stoptaking the tablets without talking to your doctor first.

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.

Serious side effects

Seek urgent medical attention if you experience any of the following side effects. The symptoms listed below may be due to serious conditions known as differentiation syndromeor QTc interval prolongation, both potentially life-threatening:

• Heart rhythm problems (QTc interval prolongation)

Contact your doctor immediately if you experience a change in your heartbeats or if you feel: dizzy, faint, or weak. These may be signs of a heart problem called QTc interval prolongation (may affect more than 1 in 10 people).

Other side effects

Tell your doctor if you notice any of the following side effects:

For patients with AML

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

• vomiting;
• neutropenia (low levels of neutrophils, a type of white blood cell that fights infections);
• thrombocytopenia (low levels of platelets in the blood that can cause bleeding and bruising);
• leukocytosis (high levels of white blood cells);
• insomnia (difficulty sleeping);
• pain in the limbs, joint pain;
• headache;
• dizziness;
• back pain.

Common(may affect more than 1 in 100 people):

• pain in the mouth or throat;
• peripheral neuropathy (nerve damage in arms and legs that can cause pain or numbness, burning sensation, or tingling);
• leukopenia (low levels of white blood cells).

For patients with bile duct cancer

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

• fatigue;
• nausea;
• abdominal pain;
• diarrhea;
• decreased appetite;
• ascites (fluid accumulation in the abdomen);
• vomiting;
• anemia (low levels of red blood cells);
• headache;
• changes in liver function tests (Aspartate aminotransferase increased);
• peripheral neuropathy (nerve damage in arms and legs that can cause pain or numbness, burning sensation, or tingling);
• skin rash;
• increased bilirubin in the blood (a breakdown product of red blood cells) that can cause yellowing of the skin and eyes.

Common(may affect more than 1 in 100 people):

• decreased white blood cell count;
• decreased platelet count;
• changes in liver function tests (Alanine aminotransferase increased);
• fall;
• hyperbilirubinemia (high levels of bilirubin in the blood);
• cholestatic jaundice (bile accumulation that causes yellowing of the skin or eyes).

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 side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Tibsovo

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 label and carton after EXP. The expiry date is the last day of the month shown.

This medicine does not require any special storage temperature. Keep the bottle tightly closed to protect it from moisture. Keep the desiccant in the bottle (see section 6).

Medicines should not be disposed of 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 additional information

Composition of Tibsovo

• The active substance is ivosidenib. Each tablet contains 250 milligrams of ivosidenib.
• The other ingredients are microcrystalline cellulose, sodium croscarmellose, hypromellose acetate succinate, anhydrous colloidal silica, magnesium stearate, sodium lauryl sulfate (E487), hypromellose, titanium dioxide (E171), lactose monohydrate, triacetin, and aluminum carmine indigo lake (E132) (see section 2 "Tibsovo contains lactose and sodium").

Appearance and package contents of the product

• The film-coated tablets are blue, oval, engraved with "IVO" on one side and "250" on the other.
• Tibsovo is presented in plastic bottles containing 60 film-coated tablets and a desiccant. The bottles are presented in a cardboard box; each box contains 1 bottle.

Marketing authorization holder

Les Laboratoires Servier

50 rue Carnot

92284 Suresnes Cedex

France

Manufacturer

Les Laboratoires Servier Industrie

905, route de Saran

45520 Gidy

France

You can request 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 on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu, and on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/)

This leaflet is available in all EU/EEA languages on the European Medicines Agency website.