Ayvakyt 200 mg comprimidos recubiertos con pelicula

Prospect: information for the patient

AYVAKYT 200 mg film-coated tablets

avapritinib

This medicine is subject to additional monitoring, which will speed up the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section 4 includes information on how to report these adverse effects.

Read this prospect carefully before starting to take this medicine, because it contains important information for you.

-Keep this prospect, as you may need to read it again.

-If you have any doubts, consult your doctor or pharmacist.

-This medicine has been prescribed only for you, and you should not give it to other people even if they have the same symptoms as you, as it may harm them.

-If you experience adverse effects, consult your doctor or pharmacist, even if they are not listed in this prospect. See section 4.

1.What is AYVAKYT and what it is used for

2.What you need to know before starting to take AYVAKYT

3.How to take AYVAKYT

4.Possible adverse effects

5.Storage of AYVAKYT

6.Contents of the pack and additional information

What is AYVAKYT

AYVAKYT is a medication that contains the active ingredient avapritinib.

What is AYVAKYT used for

AYVAKYT is used to treat adults with:

• A type of digestive system cancer 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 protein kinase called platelet-derived growth factor receptor alpha (PDGFRA).
• Aggressive systemic mastocytosis (MSA), systemic mastocytosis with associated hematologic neoplasm (MS-NHA) or mast cell leukemia (LM), 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, which produce various general symptoms and damage the affected organs.

Together, MSA, MS-NHA, and LM are referred to as advanced systemic mastocytosis (MSAv).

How AYVAKYT works

AYVAKYT inhibits the activity of a group of proteins in the body called kinases. Mast cells from patients with MSAv or the cells that make up the cancer often experience changes (mutations) in the genes involved in the production of specific kinases associated with the growth and dissemination of these cells.

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

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

Consult your doctor or pharmacist before starting to take AYVAKYT:

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

Be especially careful with this medicine:

• You may develop symptoms such asintense headache, vision problems, intense drowsiness, or intense weakness on one side of the body (signs of brain hemorrhage).If this occurs, contact your doctor immediately and temporarily stop treatment. In the case of patients with MSAv, the doctor will evaluate their 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 digestive tract, such as the stomach, rectum, or intestine.Avapritinib may also cause bleeding in the liver and tumor bleeding in patients with TEGI. Inform your doctor if you have had or have bleeding problems. Before starting avapritinib, your doctor may decide to perform blood tests. Get immediate medical help if you have the following symptoms: bloody stools or black stools, stomach pain, coughing or vomiting with blood.
• You may also developmemory loss, changes in memory, or confusion (signs of a cognitive effect).In some cases, 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 immediatelyif you experience rapid weight gain, develop facial or limb swelling, have difficulty breathing, or shortness of breath.This medicine may cause water retention (intense fluid retention).
• Avapritinib may causeabnormal heart rhythms.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 experiencesevere stomach and intestinal problems (diarrhea, nausea, and vomiting).Get immediate medical help if you experience these symptoms.
• You may develop greatersensitivity to the sunwhile taking this medicine. It is essential to cover exposed skin areas and use high-factor sunscreen.

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 should not be administered to children or adolescents under 18 years of age.

Other medicines and AYVAKYT

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

Inform 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 adverse effects:

• Boceprevir: used to treat hepatitis C.
• Cobicistat, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir: used to treat HIV/AIDS.
• Claritromycin, 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 plant-based medicine used for depression.
• Bosentan: used to treat high blood pressure.
• Efavirenz and etravirine: used to treat HIV/AIDS.
• 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 functioning of the following medicines or increase their adverse effects:

• Alfentanil: used to control pain during operations and medical procedures.
• Atazanavir: used to treat HIV/AIDS.
• 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.

Use of AYVAKYT with food and drinks

Do not drink grapefruit juice or eat grapefruit while taking AYVAKYT.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan 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 fetus. Your doctor will discuss the possible risks of taking AYVAKYT during pregnancy.

Your doctor may check if you are pregnant before starting treatment with this medicine.

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

Breastfeeding

Inform your doctor if you are breastfeeding or plan to breastfeed. It is unknown if AYVAKYT passes into breast milk. Do not breastfeed 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 this concerns you.

Driving and operating 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 operate machines. Be especially careful when driving a car or operating machines if you experience these adverse effects.

AYVAKYT contains sodium.

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

Follow exactly the administration instructions for this medication as indicated by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

What concentration of AYVAKYT to use

The recommended dose of AYVAKYT will depend on your condition: 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 TEGI

The recommended dose is 300 mg taken orally once a day.

Treatment of MSAv

The recommended dose is 200 mg taken 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 discontinue treatment. Do not change your dose or stop taking AYVAKYT unless your doctor tells you to.

Swallow the AYVAKYT tablet or tablets 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 accident, 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 usual time. Do not take a double dose within 8 hours to make up for the missed doses.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

More serious side effects

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

-intense 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 side 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;

-alteration of taste;

-increased tear production;

-abdominal pain (in the stomach);

-nausea, vomiting and retching;

-diarrhea;

-dryness affecting the eyes, lips, mouth and skin;

-heartburn;

-change in hair color;

-eruption;

-swelling (e.g., feet, ankles, face, eyes, joints);

-fatigue;

-blood tests showing a decrease in 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 falling asleep (insomnia);

-brain hemorrhage;

-decreased sensitivity, numbness, tingling or increased sensitivity to pain in arms and legs;

-unusual drowsiness or somnolence;

-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 coughing up mucus;

-gastrointestinal bleeding;

-ascites;

-constipation, flatulence (gas);

-difficulty swallowing;

-pain in the mouth, lips or tongue, candidiasis;

-increased saliva production;

-redness or itching in the skin;

-change in skin color;

-hair loss;

-pain;

-muscle spasms;

-blood in the urine;

-fever or general feeling of illness;

-changes in heart activity;

-weight loss or gain;

-blood tests showing low platelet counts, 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):

-bleeding in the tumor;

-fluid around the heart;

-bleeding in the liver.

Other side effects in patients with MSAv may include

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

-alteration of taste;

-memory loss, changes in memory or confusion (cognitive effects);

-diarrhea;

-nausea, vomiting and retching;

-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 (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;

-nasal bleeding;

-shortness of breath;

-heartburn;

-ascites;

-dryness affecting the eyes, lips, mouth and skin;

-constipation, flatulence (gas);

-abdominal pain (in the stomach);

-gastrointestinal bleeding;

-eruption;

-hair loss;

-pain;

-weight gain;

-changes in heart activity;

-bruises;

-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 in the skin;

-blood tests showing decreased kidney function.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through thenational notification system included in theAppendix V.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the label of the bottle and on the outer box after “CAD”. The expiration date is the last day of the month indicated.

This medication does not require special conditions for conservation.

Do not use this medication if you observe that the bottle is damaged or shows signs of manipulation.

Medicines should not be thrown down the drains or in the trash. Ask your pharmacist how to dispose of the containers and the medications that you no longer need. In this way, you will help to protect the environment.

Composition of AYVAKYT

• The active ingredient is avapritinib. Each film-coated tablet contains 200 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, polyvinyl alcohol and titanium dioxide (E171).
• The printing ink contains: 45% shellac (20% esterified) in ethanol, brilliant blue FCF (E133), titanium dioxide (E171), iron oxide black (E172) and propylene glycol.

Appearance of the product and contents of the pack

AYVAKYT 200 mg film-coated tablets are white, oval-shaped tablets, 16 mm in length and 8 mm in width, with “BLU” printed in blue ink on one side and “200” 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 responsible manufacturer

Blueprint Medicines (Netherlands) B.V.

Gustav Mahlerplein 2

1082 MA Amsterdam

Netherlands

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

Last update of this leaflet:

This medicine has been authorized under 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 leaflet will be updated as necessary.

Other sources of information

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