Ayvakyt 100 mg film-coated tablets

Package Leaflet: Information for the User

Introduction

Package leaflet: information for the patient

AYVAKYT 100 mg film-coated tablets

avapritinib

This medicinal product is subject to additional monitoring, which will allow for rapid identification of new safety information. You can help by reporting any adverse reactions you may experience. Section 4 at the end includes information on how to report these adverse reactions.

Read this 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 or pharmacist.
• This medicine has been prescribed for you only, and you must not give it to others, even if they have the same symptoms as you, because it could harm them.
• If you experience any adverse reactions, consult your doctor or pharmacist, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What AYVAKYT is and what it is used for

What AYVAKYT is

AYVAKYT is a medicine that contains the active substance avapritinib.

What AYVAKYT is used for

AYVAKYT is used to treat adults with:

• A type of gastrointestinal cancer called gastrointestinal stromal tumour (GIST) that cannot be treated with surgery (unresectable) or has spread to other parts of the body (metastatic), and which has a specific mutation (D842V) in the gene responsible for a kinase protein called platelet-derived growth factor receptor alpha (PDGFRA).
• Aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated haematological neoplasm (SM-AHN), or mast cell leukaemia (MCL), after having received at least one systemic treatment. These are disorders in which the body produces too many mast cells, a type of white blood cell. Symptoms occur when too many mast cells accumulate in various organs of the body, such as the liver, bone marrow, or spleen. These mast cells also release substances such as histamine, which cause various general symptoms you may experience, as well as damage to the affected organs.

Collectively, ASM, SM-AHN, and MCL are referred to as advanced systemic mastocytosis (AdvSM).

How AYVAKYT works

AYVAKYT inhibits the activity of a group of proteins in the body called kinases. In patients with AdvSM or in cancer cells, genetic changes (mutations) often occur in genes involved in producing specific kinases associated with the growth and spread of these cells.

If you have any questions about how AYVAKYT works or why this medicine has been prescribed for you, consult your doctor.

2. What you need to know before taking AYVAKYT

Do not take AYVAKYT

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

Warnings and precautions

Talk to your doctor or pharmacist before taking AYVAKYT:

• if you have had a vascular aneurysm (a bulge and weakening in the wall of a blood vessel) or bleeding in the brain within the past year;
• if you have a low platelet count.
• if you are taking a blood-thinning medicine to prevent blood clots, such as warfarin or phenprocoumon.

Take special care with this medicine:

• You may develop symptoms such as severe headache, vision problems, severe drowsiness, or severe weakness on one side of the body (signs of bleeding in the brain). If this occurs, contact your doctor immediately and temporarily stop treatment. In patients with AdvSM, your doctor will evaluate your platelet counts before starting treatment and monitor them as needed during treatment with avapritinib.
• Treatment with this medicine may increase the risk of bleeding. Avapritinib may cause bleeding in the gastrointestinal tract, such as in the stomach, rectum, or intestine. In patients with GIST, avapritinib may also cause bleeding in the liver and tumor-related bleeding. Inform your doctor if you have had or currently have bleeding problems and if you are taking warfarin, phenprocoumon, or any other medicine that thins the blood to prevent blood clots. Before starting avapritinib, your doctor may decide to perform blood tests. Seek immediate medical help if you experience the following symptoms: blood in your stools or black stools, stomach pain, coughing or vomiting blood.
• You may also develop memory loss, memory changes, or confusion (signs of a cognitive effect). Occasionally, avapritinib may affect the way you think and remember information. Contact your doctor if you experience these symptoms, or if a family member, caregiver, or someone close to you notices that you are becoming forgetful or confused.
• During treatment with this medicine, tell your doctor immediately if you gain weight rapidly, develop swelling of the face or limbs, have difficulty breathing, or experience shortness of breath. This medicine may cause fluid retention (severe fluid retention).
• Avapritinib may cause abnormalities in your heart rhythm. Your doctor may perform tests to assess these issues during your treatment with avapritinib. Inform your doctor if you feel dizzy, faint, or experience abnormal heartbeats while taking this medicine.
• You may experience severe stomach and intestinal problems (diarrhea, nausea, and vomiting). Seek immediate medical help if you experience these symptoms.
• You may become more sensitive to sunlight while taking this medicine. It is important to cover exposed skin areas and use sunscreen with a high sun protection factor (SPF).

While taking avapritinib, your doctor will ask you to have periodic blood tests. You will also be weighed regularly.

See section 4 for more information.

Children and adolescents

AYVAKYT has not been studied in children and adolescents under 18 years of age. This medicine should not be given to children or adolescents under 18 years of age.

Other medicines and AYVAKYT

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines. AYVAKYT may affect how other medicines work, and some other medicines may affect how this medicine works.

Tell your doctor or pharmacist before taking AYVAKYT if you are taking any of the following medicines:

The following medicines may increase the effects of avapritinib and may increase its side effects:

• Boceprevir: used to treat hepatitis C.
• Cobicistat, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir: used to treat HIV/AIDS infection.
• Clarithromycin, erythromycin, telithromycin: used to treat bacterial infections.
• Itraconazole, ketoconazole, posaconazole, voriconazole: used to treat serious fungal infections.
• Conivaptan: used to treat low sodium levels in the blood (hyponatremia).

The following medicines may reduce the effects of avapritinib:

• Rifampicin: used to treat tuberculosis (TB) and certain other bacterial infections.

• Carbamazepine, phenytoin, fosphenytoin, primidone, phenobarbital: used to treat epilepsy.

• St. John’s wort (Hypericum perforatum): a herbal medicine used for depression.

• Bosentan: used to treat high blood pressure.

• Efavirenz and etravirine: used to treat HIV/AIDS infection.

• Modafinil: used to treat sleep disorders.

• Dabrafenib: used to treat certain types of cancer.

• Nafcillin: used to treat certain bacterial infections.

• Dexamethasone: used to reduce inflammation.

Ask your doctor or pharmacist before taking any medicine.

Use of AYVAKYT with food and drink

You must not drink grapefruit juice or eat grapefruit during treatment with AYVAKYT.

Pregnancy, breast-feeding, and fertility

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

Pregnancy

This medicine is not recommended for use during pregnancy unless clearly necessary. Avoid becoming pregnant while receiving treatment with this medicine, as it may harm the unborn baby. Your doctor will discuss with you the potential risks of taking AYVAKYT during pregnancy.

Your doctor may check whether you are pregnant before you start treatment with this medicine.

Women of childbearing potential must use effective contraception during treatment and for at least 6 weeks after the end of treatment. Men with female partners of childbearing potential must use effective contraception during treatment and for at least 2 weeks after the end of treatment. Talk to your doctor about effective contraceptive methods that may be suitable for you.

Breast-feeding

Inform your doctor if you are breast-feeding or plan to breast-feed. It is unknown whether AYVAKYT passes into breast milk. You must not breast-feed during treatment with this medicine or for at least 2 weeks after the last dose. Talk to your doctor about the best way to feed your baby during this period.

Fertility

AYVAKYT may cause fertility problems in men and women. Consult your doctor if you have concerns about this.

Driving and using machines

AYVAKYT may cause symptoms that affect your ability to concentrate and react (see section 4). Therefore, AYVAKYT may affect your ability to drive and use machines. Exercise particular caution when driving a car or operating machinery if you experience these side effects.

AYVAKYT contains sodium.

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

3. How to take AYVAKYT

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

Which AYVAKYT strength to use

The recommended dose of AYVAKYT depends on your condition: see the information below. AYVAKYT is available in tablets of different strengths. These strengths are 25 mg, 50 mg, 100 mg, 200 mg, and 300 mg. Your doctor will advise you on the strength and number of tablets to take.

Treatment of advanced systemic mastocytosis (advSM)

The recommended dose is 200 mg taken orally once daily.

If you have liver problems, your doctor may start your treatment with a lower dose of AYVAKYT.

If you experience adverse effects, your doctor may adjust your dose, temporarily interrupt, or permanently discontinue treatment. Do not change your dose or stop taking AYVAKYT unless instructed by your doctor.

Swallow the AYVAKYT tablet(s) whole with a glass of water, on an empty stomach. Do not eat for at least 2 hours before and at least 1 hour after taking AYVAKYT.

If you vomit after taking a dose of AYVAKYT, do not take an additional dose. Take your next dose at the scheduled time.

If you take more AYVAKYT than you should

If you have accidentally taken too many tablets, contact your doctor immediately. You may require medical attention.

If you forget to take AYVAKYT

If you miss a dose of AYVAKYT, take it as soon as you remember, unless your next scheduled dose is within 8 hours. Take your next dose at the regular time. Do not take a double dose within 8 hours to make up for a missed dose.

4. Possible adverse effects

Like all medicines, this medicine can produce adverse effects, although not everyone will experience them.

Serious adverse effects

Some adverse effects may be serious. Inform your doctor immediately if you experience any of the following (see also section 2):

• severe headache, vision problems, severe drowsiness, or severe weakness on one side of the body (signs of bleeding in the brain);
• memory loss, memory changes, or confusion (signs of a cognitive effect).

Other adverse effects in patients with TEGI may include

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

• decreased appetite;
• memory loss, memory changes, or confusion (cognitive effects);
• dizziness;
• altered taste;
• increased tear production;
• abdominal pain (in the stomach);
• nausea, retching, and vomiting;
• diarrhoea;
• dryness affecting the eyes, lips, mouth, and skin;
• heartburn;
• change in hair color;
• rash;
• swelling (e.g., feet, ankles, face, eyes, joints);
• fatigue;
• blood tests showing a decrease in red blood cells (anaemia) and white blood cells;
• blood tests showing increased stress on the liver and elevated levels of bilirubin, a substance produced by the liver.

Common (may affect up to 1 in 10 people):

• red or painful eye, blurred vision;
• dehydration;
• low levels of albumin in the blood;
• depression;
• anxiety;
• difficulty falling asleep (insomnia);
• bleeding in the brain;
• decreased sensation, numbness, tingling, or increased sensitivity to pain in arms and legs;
• feeling of weakness or unusual drowsiness;
• speech disorder or hoarse voice;
• movement disorder;
• headache;
• tremor;
• bleeding in the eye;
• increased sensitivity to light;
• increased blood pressure;
• shortness of breath;
• stuffy nose;
• cough, including cough with mucus;
• gastrointestinal bleeding;
• fluid accumulation in the abdomen;
• constipation, flatulence (gas);
• difficulty swallowing;
• pain in the mouth, lips, or tongue, candidiasis;
• increased saliva production;
• redness or itching of the skin;
• change in skin color;
• hair loss;
• pain;
• muscle spasms;
• blood in the urine;
• fever or feeling of general malaise;
• changes in the electrical activity of the heart;
• weight loss or weight gain;
• blood tests showing low platelet counts, often associated with easy bruising or bleeding;
• blood tests showing altered levels of minerals in the blood;
• blood tests showing reduced kidney function;
• blood tests showing increased muscle breakdown.

Uncommon (may affect up to 1 in 100 people):

• bleeding in the tumor;
• fluid around the heart;
• bleeding in the liver.

Other adverse effects in patients with MSAv may include

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

• altered taste;
• memory loss, memory changes, or confusion (cognitive effects);
• diarrhoea;
• nausea, retching, and vomiting;
• change in hair color;
• swelling (e.g., feet, ankles, face, eyes, joints);
• fatigue;
• blood tests showing low platelet counts, often associated with easy bruising or bleeding;
• blood tests showing a decrease in red blood cells (anaemia) and white blood cells.

Common (may affect up to 1 in 10 people):

• headache;
• dizziness;
• decreased sensation, numbness, tingling, or increased sensitivity to pain in arms and legs;
• bleeding in the brain;
• increased tear production;
• nosebleeds;
• shortness of breath;
• heartburn;
• fluid accumulation in the abdomen;
• dryness affecting the eyes, lips, mouth, and skin;
• constipation, flatulence (gas);
• abdominal pain (in the stomach);
• gastrointestinal bleeding;
• rash;
• hair loss;
• pain;
• weight gain;
• changes in the electrical activity of the heart;
• bruising;
• blood tests showing increased stress on the liver and elevated levels of bilirubin, a substance produced by the liver.

Uncommon (may affect up to 1 in 100 people):

• fluid around the heart;
• redness or itching of the skin;
• blood tests showing reduced kidney function.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may 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 AYVAKYT

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

Do not use this medicine after the expiry date stated on the label of the bottle and on the outer carton, following “EXP”. The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage conditions.

Do not use this medicine if you notice that the bottle is damaged or shows signs of tampering.

Medicines must 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 AYVAKYT

• The active substance is avapritinib. Each film-coated tablet contains 25 mg of avapritinib.

• The other components are:

• Tablet core: microcrystalline cellulose, copovidone, sodium croscarmellose, and magnesium stearate (see section 2 “AYVAKYT contains sodium”).

• Tablet coating: talc, macrogol 3350, poly(vinyl alcohol), and titanium dioxide (E171).

Appearance of the product and contents of the pack

AYVAKYT 25 mg film-coated tablets are white, round tablets, 5 mm in diameter, with the inscription “BLU” engraved on one side and “25” on the other.

AYVAKYT is supplied in a bottle containing 30 film-coated tablets. Each carton contains one bottle.

Keep the desiccant in the bottle.

Marketing Authorization Holder and Manufacturer Responsible

Blueprint Medicines (Netherlands) B.V.

Gustav Mahlerplein 2

1082 MA Amsterdam

The Netherlands

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

Date of the most recent review of this leaflet:

This medicinal product has been authorised under a "conditional approval". This type of approval means that further information on this medicinal product is expected.

The European Medicines Agency will review the new information on this medicinal product at least once a year, and this leaflet will be updated as necessary.

Other sources of information

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