AYVAKYT 50 mg FILM-COATED TABLETS

Introduction

Patient Information: Summary of Product Characteristics

AYVAKYT 50 mg film-coated tablets

avapritinib

This medicinal product is subject to additional monitoring, which will allow for quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for 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 AYVAKYT and what is it used for
2. What you need to know before you take AYVAKYT
3. How to take AYVAKYT
4. Possible side effects
5. Storage and disposal of AYVAKYT
6. Contents of the pack and other information

1. What is AYVAKYT and what is it used for

What is AYVAKYT

AYVAKYT is a medicine that contains the active substance avapritinib.

What is AYVAKYT used for

AYVAKYT is used to treat adults with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL) who have received at least one prior systemic therapy. 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 enter various organs of the body, such as the liver, bone marrow, or spleen. These mast cells also release substances, such as histamine, that produce various general symptoms that you may have, in addition to damaging the organs in question.

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

How AYVAKYT works

AYVAKYT inhibits the activity of a group of proteins in the body called kinases. The mast cells of patients with ASM often undergo changes (mutations) in the genes involved in the production of 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, ask your doctor.

2. What you need to know before you take AYVAKYT

Do not take AYVAKYT

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

Warnings and precautions

Talk to your doctor or pharmacist before starting treatment with AYVAKYT:

• if you have had a vascular aneurysm(bulging and weakening of the wall of a blood vessel) or bleeding in the brainin the last year;
• if you have a low platelet count;
• if you are taking a medicine that thins the blood to prevent blood clots, such as warfarin or phenprocoumon

Be careful with this medicine:

• You may develop symptoms such as severe headache, vision problems, excessive drowsiness, or weakness on one side of the body (signs of bleeding in the brain).If this happens, contact your doctor immediately and temporarily stop treatment. In the case of patients with ASM, the doctor will evaluate your platelet counts before starting treatment and monitor them as necessary during treatment with avapritinib.
• Treatment with this medicine may increase the risk of bleeding.Avapritinib may cause bleeding in the digestive system, such as the stomach, rectum, or intestine. In patients with ASM, avapritinib may also cause bleeding in the liver, as well as tumor bleeding. Tell your doctor if you have had or have bleeding problems. Before starting treatment with avapritinib, your doctor may decide to perform blood tests. Get medical help right away if you have the following symptoms: blood in your stool 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 change the way you think and remember information. Contact your doctor if you experience these symptoms or if a family member, caregiver, or someone who knows you notices that you are becoming forgetful or confused.
• During treatment with this medicine, tell your doctor immediately if you gain weight very quickly, develop swelling of the face or limbs, have difficulty breathing, or shortness of breath. This medicine may cause water retention (severe fluid retention).
• Avapritinib may cause abnormalities in your heart rhythm.Your doctor may perform tests to evaluate these problems during treatment with avapritinib. Tell your doctor if you feel dizzy, faint, or have abnormal heartbeats while taking this medicine.
• You may experience severe stomach and intestinal problems (diarrhea, nausea, and vomiting).Get medical help right away if you experience these symptoms.
• You may develop increased sensitivity to the sunwhile taking this medicine. It is essential 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 regular 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 must 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 take any other medicines, AYVAKYT may affect the way 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 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 severe 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 some 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.

This medicine may affect the way the following medicines work or increase their side effects:

• Alfentanil: used to control pain during operations and medical procedures.
• Atazanavir: used to treat HIV/AIDS infection.
• Midazolam: used for anesthesia, sedation, or to reduce anxiety.
• Simvastatin: used to treat high cholesterol.
• Sirolimus, tacrolimus: used to prevent organ transplant rejection.

Ask your doctor or pharmacist before taking any medicine.

Using AYVAKYT with food and drinks

Do not drink grapefruit juice or eat grapefruit during treatment with AYVAKYT.

Pregnancy, breastfeeding, and fertility

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

Pregnancy

This medicine is not recommended 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 if you are pregnant before you start treatment with this medicine.

Women of childbearing potential must use effective contraceptive methods during treatment and for at least 6 weeks after the end of treatment. Male patients with female partners of childbearing potential must use effective contraceptive methods 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.

Breastfeeding

Tell your doctor if you are breastfeeding or plan to breastfeed. It is not known if AYVAKYT passes into breast milk. Do not breastfeed during treatment with this medicine and for at least 2 weeks after the last dose. Talk to your doctor about the best way to feed your baby during this time.

Fertility

AYVAKYT may cause fertility problems in men and women. Ask your doctor for advice if this is a concern for you.

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. Be careful when driving a car or using machines if you experience these side effects.

AYVAKYT contains sodium.

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

3. How to take AYVAKYT

Follow the instructions for administration of this medicine exactly as told by your doctor or pharmacist. If you are unsure, ask your doctor or pharmacist again.

What concentration of AYVAKYT to use

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

Treatment of ASM

The recommended dose is 200 mg orally once daily.

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

If you experience side effects, your doctor may change your dose, temporarily stop, or permanently stop treatment. Do not change your dose or stop taking AYVAKYT unless your doctor tells you to.

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 the next dose at your scheduled time.

If you take more AYVAKYT than you should

If you have taken too many tablets by mistake, talk to your doctor immediately. You may need 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 the next dose at your scheduled time. Do not take a double dose within 8 hours to make up for missed doses.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

More serious side effects

Some side effects can be serious. Tell your doctor immediately if you experience any of the following(see also section 2):

• severe headache, vision problems, excessive drowsiness, or 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 side effects may include:

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

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

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

• headache;
• dizziness;
• decreased sensitivity, 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 abdomen);
• gastrointestinal bleeding;
• rash;
• hair loss;
• pain;
• weight gain;
• changes in heart rhythm;
• bruising;
• blood tests showing increased stress on the liver and high 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 decreased kidney function.

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 via 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 and disposal of AYVAKYT

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 carton and blister after “EXP”. The expiry date refers to the last day of the month shown.

This medicine does not require any special storage conditions.

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

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. Packaging Content and Additional Information

AYVAKYT Composition

• The active ingredient is avapritinib. Each film-coated tablet contains 50 mg of avapritinib.
• The other components are:

• The tablet core contains: microcrystalline cellulose, copovidone, sodium croscarmellose, and magnesium stearate (see section 2 "AYVAKYT contains sodium").
• The tablet coating contains: talc, macrogol 3350, poly(vinyl) alcohol, and titanium dioxide (E171).

Product Appearance and Packaging Content

AYVAKYT 50 mg film-coated tablets are white and round, 6 mm in diameter, with the text "BLU" engraved on one side and "50" on the other.

AYVAKYT is supplied in a bottle with 30 film-coated tablets. Each box contains one bottle.

Keep the desiccant in the bottle.

Marketing Authorization Holder and Manufacturer

Blueprint Medicines (Netherlands) B.V.

Gustav Mahlerplein 2

1082 MA Amsterdam

Netherlands

For more information about this medicinal product, please contact the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet:

This medicinal product has been authorized under a "conditional approval". This type of approval means that more information is expected to be obtained for this medicinal product.

The European Medicines Agency will review the new information for 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 European Medicines Agency website: http://www.ema.europa.eu/.