AYVAKYT 100 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the Patient

AYVAKYT 100 mg film-coated tablets

avapritinib

This medicine 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. The last section of this leaflet includes 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 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 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 AYVAKYT is used for

AYVAKYT is used to treat adults with:

• A type of cancer of the digestive system called gastrointestinal stromal tumor (GIST) when it cannot be treated with surgery (unresectable) or has spread to other parts of the body (metastatic) and has a specific mutation (D842V) in the gene responsible for the platelet-derived growth factor receptor alpha (PDGFRA) kinase protein.
• Aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN) or mast cell leukemia (MCL), after receiving 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 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 (ASMv).

How AYVAKYT works

AYVAKYT inhibits the activity of a group of proteins in the body called kinases. The mast cells of patients with ASMv or the cells that make up the cancer 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 to take 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 clot formation, such as warfarin or phenprocoumon.

Be particularly careful with this medicine:

• You may develop symptoms such as severe headache, vision problems, excessive drowsiness, or severe weakness on one side of the body (signs of bleeding in the brain). If this happens, contact your doctor immediately and temporarily interrupt treatment. In the case of patients with ASMv, the doctor will evaluate your platelet counts before starting treatment and monitor them as necessary during your 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 GIST, avapritinib may also cause bleeding in the liver, as well as tumor bleeding. Inform your doctor if you have had or have bleeding problems and if you are taking warfarin, phenprocoumon, or another medicine that thins the blood to prevent blood clots. Before starting to take avapritinib, your doctor may decide to perform blood tests. Get medical help immediately if you have the following symptoms: blood in the stool or black-colored stool, stomach pain, coughing or vomiting blood.
• You may also develop memory loss, changes in memory, or confusion (signs of cognitive effects). 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, inform 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 your treatment with avapritinib. Inform 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 immediately if you experience these symptoms.
• You may develop increased sensitivity to the sun while taking this medicine. It is important that you 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 the way 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 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 age must use effective contraceptive methods during treatment and for at least 6 weeks after finishing treatment. Male patients with female partners of childbearing age must use effective contraceptive methods during treatment and for at least 2 weeks after finishing 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. You must not breastfeed while taking 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 if this worries 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 particularly 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 exactly the administration instructions of this medicine given 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 GIST

The recommended dose is 300 mg orally once a day.

Treatment of ASMv

The recommended dose is 200 mg orally once a day.

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 interrupt, 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 the scheduled time.

If you take more AYVAKYT than you should

If you have taken too many tablets accidentally, 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 the scheduled time. Do not take a double dose within 8 hours to make up for missed doses.

4. Possible Adverse Effects

Like all medicines, this medicine may cause adverse effects, although not all people may experience them.

More Serious Adverse Effects

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

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

Other Adverse Effects in Patients with TEGI May Include

Very Common(may affect more than 1 person in 10):

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

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

• red or painful eye, blurred vision;
• dehydration;
• low albumin levels in blood;
• depression;
• anxiety;
• difficulty staying asleep (insomnia);
• brain bleeding;
• decreased sensitivity, numbness, tingling, or increased sensitivity to pain in arms and legs;
• feeling of weakness or unusual drowsiness;
• speech or voice disorder;
• movement disorder;
• headache;
• tremor;
• eye bleeding;
• increased sensitivity to light;
• increased blood pressure;
• shortness of breath;
• stuffy nose;
• cough, including cough producing mucus;
• gastrointestinal bleeding;
• increased fluid 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;
• skin color change;
• hair loss;
• pain;
• muscle spasms;
• blood in the urine;
• fever or general feeling of discomfort;
• changes in heart electrical activity;
• weight loss or gain;
• blood test showing low platelet count, often associated with easy bruising or bleeding;
• blood test showing altered mineral levels in the blood;
• blood test showing decreased kidney function;
• blood test showing increased muscle breakdown.

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

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

Other Adverse Effects in Patients with MSAv May Include

Very Common(may affect more than 1 person in 10):

• altered taste;
• memory loss, changes in memory or confusion (cognitive effects);
• diarrhea;
• nausea, retching, and vomiting;
• hair color change;
• swelling (e.g., feet, ankles, face, eyes, joints);
• fatigue;
• blood test showing low platelet count, often associated with easy bruising or bleeding;
• blood test showing decreased 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;
• brain bleeding;
• increased tear production;
• nosebleed;
• shortness of breath;
• heartburn;
• increased fluid 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 electrical activity;
• bruising;
• blood test showing increased liver stress and elevated bilirubin levels, 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 test showing decreased kidney function.

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of AYVAKYT

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiration date shown on the label of the vial and on the outer carton after "EXP". The expiration date is the last day of the month indicated.

This medicine does not require special storage conditions.

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

Medicines should not be disposed of through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicines. This will help protect the environment.

6. Package Contents and Additional Information

Composition of AYVAKYT

• The active ingredient is avapritinib. Each film-coated tablet contains 100 mg of avapritinib.
• The other ingredients are:

• The core of the tablet 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).
• The printing ink contains: 45% lacquer (20% esterified) in ethanol, brilliant blue FCF (E133), titanium dioxide (E171), black iron oxide (E172), and propylene glycol.

Appearance and Package Contents

AYVAKYT 100 mg film-coated tablets are white and round, 9 mm in diameter, with "BLU" printed in blue ink on one side and "100" on the other.

AYVAKYT is supplied in a bottle with 30 film-coated tablets. Each carton 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

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Prospectus:

This medicine has been authorized with a "conditional approval". This type of approval means that more information is expected to be obtained about this medicine.

The European Medicines Agency will review the new information about this medicine at least once a year, and this prospectus will be updated as necessary.

Other Sources of Information

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