Tibsovo

Patient Information Leaflet

Tibsovo 250 mg film-coated tablets

ivosidenib
This medicinal product is subject to additional monitoring. This will allow for the rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before you start taking this medicine, as 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 nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or nurse. See section 4.

Contents of this leaflet

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

1. What Tibsovo is and what it is used for

What Tibsovo is
Tibsovo contains the active substance ivosidenib. It is a medicine used to treat specific types of
cancer that have a mutated (altered) form of the gene that produces a protein known as IDH1, which plays an important role in cellular energy production. When the IDH1 gene is mutated, the IDH1 protein is altered and does not function properly, leading to changes in the cell that can cause cancer development. Tibsovo blocks the mutated form of the IDH1 protein and helps slow down or stop cancer growth.
What Tibsovo is used for
Tibsovo is used to treat adults with:

• Acute myeloid leukaemia (AML). When used in patients with AML, Tibsovo is given in combination with another anticancer medicine called "azacitidine".
• Bile duct cancer (also known as "cholangiocarcinoma"). Tibsovo is used alone to treat patients whose bile duct cancer has spread to other parts of the body and who have been previously treated with at least one prior therapy. Tibsovo is used only in patients with AML or bile duct cancer associated with a change (mutation) in the IDH1 protein.

2. What you need to know before taking Tibsovo

Your doctor will perform a test to check for the presence of a mutation in the IDH1 protein before deciding whether this medicine is the appropriate treatment for your condition.
Do not take Tibsovo:

• if you are allergic to ivosidenib or to any of the other ingredients of 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 disease known as "congenital long QT syndrome";
• if you have a family history of sudden death or abnormal or irregular heartbeat in the lower chambers of the heart;
• if you have a serious abnormal electrical activity of the heart affecting heart rhythm known as "QT prolongation".

Do not take Tibsovo if any of the above apply to you. If in doubt, consult your doctor or nurse.
Warnings and precautions
Differentiation syndrome in patients with AML:
Tibsovo may cause a very serious condition known as differentiation syndrome in patients with AML. This is a condition affecting blood cells which, if untreated, may be potentially fatal.
Contact a doctor immediately if any of the following symptoms occur after taking
Tibsovo:

• fever,
• cough,
• breathing difficulties,
• skin rash,
• reduced urination,
• dizziness or lightheadedness,
• rapid weight gain,
• swelling of the arms or legs.

These may be signs of differentiation syndrome.
The package includes a patient alert card to carry at all times. It contains important information for you and healthcare professionals about what to do if any symptoms of differentiation syndrome occur (see section 4).
QTc interval prolongation:
Tibsovo may cause a serious condition known as QTc interval prolongation, which may lead to irregular heartbeats and life-threatening arrhythmias (abnormal electrical activity of the heart affecting its rhythm). Your doctor must monitor your heart's electrical activity before and during treatment with Tibsovo (see "Regular tests").
Contact a doctor immediately if, after taking Tibsovo, you experience dizziness, lightheadedness, palpitations, or fainting (see also section 4).
During treatment, inform your doctors that you are taking Tibsovo before starting any new medicines, as these may increase the risk of cardiac arrhythmias.
If you experience any of the serious side effects listed above, your doctor may prescribe additional medicines to treat these conditions and may ask you to temporarily or permanently stop taking Tibsovo.
Consult your doctor before taking Tibsovo if:

• you have heart conditions or problems with abnormal electrolyte levels (such as sodium, potassium, calcium, or magnesium);
• you are taking medicines that may affect the heart (e.g., those used to prevent arrhythmias known as antiarrhythmics, certain antibiotics, antifungals, or medicines used to prevent nausea and vomiting – see "Other medicines and Tibsovo");
• you have kidney problems;
• you have liver problems.

Regular tests
Your doctor will closely monitor you before and during treatment with Tibsovo.
You will need to have regular electrocardiograms (ECGs; recordings of the heart's electrical activity) to monitor your heart rhythm. An ECG will be performed before starting Tibsovo treatment, once a week for the first three weeks of treatment, and then once a month. Additional ECGs may be required as directed by your doctor. If you start taking medicines that may affect the heart, an ECG will be prescribed before starting and during treatment with the new medicine as needed.
You will also need regular blood tests before starting Tibsovo and periodically thereafter.
If necessary, your doctor may reduce the dose of Tibsovo or temporarily or permanently discontinue treatment.
Children and adolescents
Do not give this medicine to children and adolescents under 18 years of age, as there is no information available on its use in this age group.
Other medicines and Tibsovo
Inform your doctor if you are taking, have recently taken, or might take any other medicines. Taking other drugs may reduce the effectiveness of Tibsovo, increase the risk of side effects, or Tibsovo may affect the effectiveness of other medicines.
In particular, you must inform your doctor if you are taking any of the following medicines so that your doctor can decide whether treatment adjustments are needed:

• antibiotics used 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 heart rhythm, known as antiarrhythmics (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 transplants, known as immunosuppressants (e.g. cyclosporine, everolimus, sirolimus, tacrolimus);
• medicines used for HIV (e.g. raltegravir, ritonavir);
• alfentanil (used for anesthesia in surgery);
• fentanyl (used as an analgesic for severe pain);
• pimozide (used for schizophrenia);
• anticancer medicines (e.g. cyclophosphamide, ifosfamide, paclitaxel);
• methadone (used for heroin or morphine addiction replacement therapy, or for severe pain);
• medicines used for type 2 diabetes (e.g. pioglitazone, repaglinide);
• omeprazole (used for gastric ulcers and gastroesophageal reflux);
• furosemide (used for fluid retention known as edema);
• medicines used for hypercholesterolemia, known as statins (e.g. atorvastatin, pravastatin, rosuvastatin);
• lamotrigine (used for epilepsy).

Tibsovo with food and drink
Do not eat grapefruit or drink grapefruit juice during treatment with Tibsovo, as it may impair the effectiveness of this medicine.
Pregnancy, breastfeeding and fertility
You are advised not to use Tibsovo during pregnancy as it may harm the unborn baby. Women of childbearing potential must undergo a pregnancy test before starting treatment with Tibsovo and must avoid becoming pregnant during therapy.
If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, consult your doctor before taking this medicine. Contact your doctor or nurse immediately if you become pregnant during treatment with Tibsovo.
Contraception
Tibsovo must not be used during pregnancy because it may harm the unborn baby. Women of childbearing potential or men with partners of childbearing potential must use effective contraception to prevent pregnancy during treatment with Tibsovo and for at least 1 month after the last dose.
Tibsovo may reduce the effectiveness of hormonal contraceptives. If you or your partner use a hormonal contraceptive (e.g. contraceptive pills, patches, or contraceptive implants), you must also use a barrier contraceptive method (e.g. condoms or diaphragm) to prevent pregnancy. Consult your doctor or nurse for advice on the most suitable contraceptive method for your needs.
Breastfeeding
There is no information available on whether Tibsovo is excreted in human breast milk. Do not breastfeed during treatment with Tibsovo and for at least 1 month after the last dose.
Fertility
It is unknown whether Tibsovo may affect fertility. If you have concerns about fertility while taking Tibsovo, consult your doctor.
Driving and using machines
This medicine has a minor influence on the ability to drive or use machines. If you feel unwell after taking Tibsovo, do not drive or operate machinery until you feel well again.
Tibsovo contains lactose and sodium
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.
This medicine contains less than 1 mmol of sodium (23 mg) per tablet and is therefore essentially "sodium-free".

3. How to take Tibsovo

Take this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor or nurse.
The recommended dose is 2 tablets (ivosidenib 500 mg) taken once daily, always more or less at the same time.
Your doctor may prescribe 1 tablet (ivosidenib 250 mg) if you are taking other medicines or to help you better tolerate certain possible side effects.

• Take the tablets on an empty stomach. Do not eat for 2 hours before and 1 hour after taking the tablets.
• Swallow the tablets whole with water.
• Do not ingest the desiccant contained 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 take additional tablets. Take the next dose as usual the following day.

If you take more Tibsovo than you should
If you accidentally take more tablets than prescribed by your doctor, contact your doctor immediately, bringing the medicine bottle with you.
If you forget to take Tibsovo
If you forget or do not take a dose at the usual time, take the tablets as soon as possible, unless the next dose is due within 12 hours. Do not take two doses within 12 hours. Take the next dose as usual the following day.
How long to take Tibsovo
You must continue taking this medicine until your doctor tells you to stop. Do not stop taking the tablets before discussing it with your doctor.
If you have any questions about the use of this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Serious side effects
Seek immediate medical advice if you experience any of the following side effects. The symptoms
listed below may be due to serious conditions known as differentiation syndrome or QTc interval prolongation, both of which can be potentially fatal:
Differentiation syndrome:
Seek immediate medical attention if you develop any of the following symptoms:

• fever,
• cough,
• breathing problems,
• rash,
• decreased urine output,
• dizziness or lightheadedness,
• rapid weight gain,
• swelling of the arms or legs.

Some or all of these symptoms may be signs of a condition called differentiation syndrome (may affect more than 1 in 10 people).
Differentiation syndrome in patients with AML has occurred up to 46 days after starting Tibsovo.

• Heart rhythm problems (QTc interval prolongation) Seek immediate medical attention if you experience changes in heartbeat or if you feel: dizziness, lightheadedness, or fainting. These may be signs of a heart problem called QT prolongation (may affect more than 1 in 10 people).

Other side effects
Contact your doctor if you notice any of the following side effects:
In 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, which may cause bleeding and bruising);
• leukocytosis (high levels of white blood cells);
• insomnia (difficulty sleeping);
• pain in extremities, joint pain;
• headache;
• dizziness;
• back pain.

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

• mouth or throat pain;
• peripheral neuropathy (nerve damage in arms and legs causing pain or numbness, burning sensations, and tingling);
• leucopenia (low levels of white blood cells).

In patients with cholangiocarcinoma
Very common (may affect more than 1 in 10 people):

• fatigue;
• nausea;
• abdominal pain;
• diarrhoea;
• decreased appetite;
• ascites (fluid accumulation in the abdomen);
• vomiting;
• anaemia (low levels of red blood cells);
• changes in liver function tests (increased aspartate aminotransferase);
• peripheral neuropathy (nerve damage in arms and legs causing pain or numbness, burning sensations, and tingling);
• rash;
• increased blood bilirubin (a breakdown product of red blood cells), which may 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 (increased alanine aminotransferase);
• fainting;
• hyperbilirubinemia (high levels of bilirubin in the blood);
• cholestatic jaundice (bile accumulation leading to yellowing of the skin or eyes).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or nurse. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Tibsovo

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and on the carton of the
bottle after Exp. The expiry date refers to the last day of that month.
This medicine does not require any special storage temperature conditions. Keep the
bottle tightly closed to protect it from moisture. Keep the desiccant inside the bottle
(see section 6).
Do not dispose of any medicine 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 other information

What Tibsovo contains

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

Description of the appearance of Tibsovo and contents of the pack

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

Marketing Authorisation Holder
Les Laboratoires Servier
50 rue Carnot
92284 Suresnes Cedex
France

Manufacturer
Les Laboratoires Servier Industrie
905 route de Saran
45520 Gidy
France

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
S.A. Servier Benelux N.V. UAB “SERVIER PHARMA”
Tel: +32 (0)2 529 43 11 Tel: +370 (5) 2 63 86 28

България Luxembourg/Luxemburg
Сервие Медикал ЕООД S.A. Servier Benelux N.V.
Тел.: +359 2 921 57 00 Tel: +32 (0)2 529 43 11

Česká republika Magyarország
Servier s.r.o. Servier Hungaria Kft.
Tel: +420 222 118 111 Tel: +36 1 238 7799

Danmark Malta
Servier Danmark A/S V.J. Salomone Pharma Ltd
Tlf: +45 36 44 22 60 Tel: +356 21 22 01 74

Deutschland Nederland
Servier Deutschland GmbH Servier Nederland Farma B.V.
Tel: +49 (0)89 57095 01 Tel: +31 (0)71 5246700

Eesti Norge
Servier Laboratories OÜ Servier Danmark A/S
Tel:+ 372 664 5040 Tlf: +45 36 44 22 60

Eλλάδα Österreich
ΣΕΡΒΙΕ ΕΛΛΑΣ ΦΑΡΜΑΚΕΥΤΙΚΗ ΕΠΕ Servier Austria GmbH
Τηλ: +30 210 939 1000 Tel: +43 (1) 524 39 99

España Polska
Laboratorios Servier S.L. Servier Polska Sp. z o.o.
Tel: +34 91 748 96 30 Tel: +48 (0) 22 594 90 00

France Portugal
Les Laboratoires Servier Servier Portugal, Lda
Tel: +33 (0)1 55 72 60 00 Tel.: +351 21 312 20 00

Hrvatska România
Servier Pharma, d. o. o. Servier Pharma SRL
Tel.: +385 (0)1 3016 222 Tel: +4 021 528 52 80

Ireland Slovenija
Servier Laboratories (Ireland) Ltd. Servier Pharma d. o. o.
Tel: +353 (0)1 663 8110 Tel.: +386 (0)1 563 48 11

Ísland Slovenská republika
Servier Laboratories Servier Slovensko spol. s r.o.
c/o Icepharma hf Tel.: +421 (0) 2 5920 41 11
Sími: +354 540 8000

Italia Suomi/Finland
Servier Italia S.p.A. Servier Finland Oy
Tel: +39 06 669081 P. /Tel: +358 (0)9 279 80 80

Κύπρος Sverige
C.A. Papaellinas Ltd. Servier Sverige AB
Τηλ: +357 22741741 Tel: +46 (0)8 522 508 00

Latvija
SIA Servier Latvia
Tel: +371 67502039

Other sources of information
Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.
This summary of product characteristics is available in all EU/EEA languages on the European Medicines Agency website.