AYVAKYT 200 mg FILM-COATED TABLETS

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 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 brain bleeding).If this happens, contact your doctor immediately and temporarily stop 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. Before starting 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 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, tell your doctor right away 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 right away if you experience these symptoms.
• You may develop increased sensitivity to the sunwhile taking this medicine. It is essential 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 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

Always take this medicine exactly as your doctor or pharmacist has told you. If you are not sure, check with your doctor or pharmacist.

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 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 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 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 the 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 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 in 10 people):

• 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 tests showing decreased red blood cells (anemia) and white blood cells;
• blood tests 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 the 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 feeling of general malaise;
• changes in heart electrical activity;
• weight loss or gain;
• blood tests showing low platelet count, often associated with easy bruising or bleeding;
• blood tests showing altered mineral levels in the blood;
• blood tests showing decreased kidney function;
• blood tests 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 in 10 people):

• 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 tests showing low platelet count, often associated with easy bruising or bleeding;
• blood tests 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 tests 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 tests 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 stated on the label and 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 bottle 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 the packaging and any unused medicine. 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 200 mg of avapritinib.
• The other ingredients 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).
• The printing ink contains: 45% lacquer (20% esterified) in ethanol, brilliant blue FCF (E133), titanium dioxide (E171), iron oxide black (E172), and propylene glycol.

Appearance and Package Contents

AYVAKYT 200 mg film-coated tablets are white, oval tablets, 16 mm long and 8 mm wide, with "BLU" printed in blue ink on one side and "200" 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 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/.