RYDAPT 25 mg Soft Capsule

Зміст інструкції

1. Rydapt 25 mg soft capsules
   1. What is Rydapt and what is it used for
   2. What you need to know before you take Rydapt
   3. How to take Rydapt
   4. Possible side effects
   5. How to store Rydapt
   6. Package contents and other information

Rydapt 25 mg soft capsules

midostaurin

Read this leaflet carefully before you start to take this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

1. What is Rydapt and what is it used for

What is Rydapt
Rydapt contains the active ingredient midostaurin. It belongs to a class of medicines called
protein kinase inhibitors.

What is Rydapt used for
Rydapt is used to treat acute myeloid leukemia (AML) in adults who have a defect in
a gene called FLT3. Acute myeloid leukemia is a form of cancer of certain white blood cells (called myeloid cells) in which the body overproduces an abnormal type of these cells.
Rydapt is also used in adults to treat aggressive systemic mastocytosis (ASM),
systemic mastocytosis associated with hematologic neoplasms (SM-AHN), or mast cell leukemia
(MCL). These are disorders in which the body produces too many mast cells, a type of white blood cell. The
symptoms occur when too many mast cells enter organs such as the liver, bone marrow, or
spleen and release substances such as histamine into the blood.

How Rydapt works
Midostaurin blocks the action of certain enzymes (kinases) in abnormal cells and stops their division and
growth.
In AML at the beginning of treatment, Rydapt is always used together with chemotherapeutic agents (medicines
for the treatment of cancer).
If you have any questions about how Rydapt works or why this medicine has been prescribed to you, ask your doctor, pharmacist or nurse.

2. What you need to know before you take Rydapt

Follow the doctor's instructions carefully. These instructions may be different from the general information in this leaflet.

Do not take Rydapt

• if you are allergic to midostaurin or any of the other ingredients of this medicine (listed in section 6). If you think you may be allergic, ask your doctor for advice.
• if you are already taking any of the following medicines:
• medicines used for the treatment of tuberculosis, such as rifampicin;
• medicines used for the treatment of epilepsy, such as carbamazepine or phenytoin;
• enzalutamide, a medicine used to treat prostate cancer;
• St John's wort (also known as Hypericum perforatum), a herbal medicine used for the treatment of depression. These medicines must be avoided during treatment with Rydapt. Contact your doctor if you have been told that you must start taking one of these during treatment with Rydapt.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking Rydapt:

• if you have infections.
• if you have heart disease.
• if you have lung problems or breathing problems.
• if you have kidney problems.

Tell your doctor, pharmacist or nurse immediately if you have any of these symptoms during treatment with Rydapt:

• if you have a fever, sore throat or mouth ulcers, because these may indicate that your white blood cell count is low.
• if you have new or worsening symptoms such as fever, cough with or without mucus, chest pain, difficulty breathing or shortness of breath, because these may be signs of lung problems.
• if you have or develop chest pain or discomfort, lightheadedness, fainting, dizziness, bluish discoloration of the lips, hands or feet, shortness of breath, or swelling of the lower legs (edema) or skin, because these may be signs of heart problems. Your doctor may need to change, temporarily suspend or completely stop treatment with Rydapt.

Monitoring during treatment with Rydapt
Your doctor will perform regular blood tests during treatment with Rydapt to monitor the amount of blood cells (white blood cells, red blood cells and platelets) and electrolytes (e.g. calcium, potassium and magnesium) in the body. The function of the heart and lungs will also be checked regularly.

Children and adolescents
Rydapt must not be used in children and adolescents under 18 years of age who are also receiving other chemotherapy, because it can cause a severe reduction in some types of blood cells.

Other medicines and Rydapt
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This is because Rydapt can affect the way some medicines work. Some other medicines can also affect the activity of Rydapt.
The following medicines must be avoided during treatment with Rydapt:

• medicines used for the treatment of tuberculosis, such as rifampicin;
• medicines used for the treatment of epilepsy, such as carbamazepine or phenytoin;
• enzalutamide, a medicine used to treat prostate cancer;
• St John's wort (also known as Hypericum perforatum), a herbal medicine used for the treatment of depression.

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

• some medicines used to treat infections, such as ketoconazole or clarithromycin;
• some medicines used to treat HIV, such as ritonavir or efavirenz;
• some medicines used to treat depression, such as nefazodone or bupropion;
• some medicines used to control fat levels in the blood, such as atorvastatin or rosuvastatin;
• tizanidine, a medicine used to relax muscles;
• chlorzoxazone, a medicine used to treat discomfort caused by muscle spasms.

If you are taking any of these medicines, your doctor may prescribe you a different medicine during treatment with Rydapt.
You should also tell your doctor if you are already taking Rydapt and have been prescribed a new medicine that you have not taken before during treatment with Rydapt.
Ask your doctor or pharmacist if you are not sure whether the medicine you are taking is one of the medicines listed above.

Pregnancy and breastfeeding
Rydapt can be harmful to the fetus and is not recommended during pregnancy. If you are pregnant, suspect you may be pregnant or are planning to become pregnant, ask your doctor for advice before taking this medicine.
Rydapt can be harmful to the baby. Do not breastfeed with breast milk during treatment with Rydapt and for at least 4 months after stopping treatment.

Contraception in women
If you become pregnant during treatment with Rydapt, this may be harmful to the baby. Your doctor will ask you to take a pregnancy test before starting treatment with Rydapt to make sure you are not pregnant. You should use effective contraception during treatment with Rydapt and for at least 4 months after stopping treatment. Your doctor will discuss with you the most suitable method of contraception to use.
If you become pregnant or think you may be pregnant, tell your doctor immediately.

Fertility
Rydapt may reduce fertility in men and women. Discuss this with your doctor before starting treatment.

Driving and using machines
Be particularly careful when driving and using machines because you may experience dizziness and vertigo while taking Rydapt.

Rydapt contains anhydrous ethanol (alcohol)
This medicine contains 666 mg of alcohol (ethanol) in each 200 mg dose (maximum daily dose), which is equivalent to 14 vol. % of anhydrous ethanol. The amount in a 200 mg dose of this medicine is equivalent to 17 mL of beer or 7 mL of wine. The small amount of alcohol in this medicine will not produce significant effects. Alcohol can be harmful if you have alcohol-related problems, epilepsy or liver problems, or if you are pregnant or breastfeeding.

Rydapt contains macrogol hydroxystearate (castor oil)
This medicine contains macrogol hydroxystearate, which can cause stomach upset and diarrhea.

3. How to take Rydapt

Take this medicine following exactly the instructions of your doctor or pharmacist. If you
have any doubts, ask your doctor or pharmacist.
Do not exceed the dose prescribed by your doctor.

How much Rydapt to take
Your doctor will tell you exactly how many capsules you will need to take.

• Patients with AMLThe usual daily dose is 50 mg (2 capsules) twice a day.
• Patients with ASM, SM-AHN or MCLThe usual daily dose is 100 mg (4 capsules) twice a day.

Depending on how you respond to Rydapt, your doctor may lower the dose or temporarily suspend
treatment.

Taking the medicine

• Taking Rydapt at the same time each day will help you remember to take the medicine.
• Take Rydapt twice a day at intervals of approximately 12 hours (for example with breakfast and with the evening meal).
• Take Rydapt with food.
• Swallow the capsules whole with a glass of water. Do not open, crush or chew the capsules to ensure adequate dosage and to avoid the unpleasant taste of the capsule contents.
• For patients with AML, Rydapt is taken with chemotherapeutic medicines. It is very important to follow your doctor’s recommendations.
• If you vomit after swallowing the capsules, do not take more capsules until the next scheduled dose.

For how long to take Rydapt

• Continue to take Rydapt for the entire time for which it has been prescribed by your doctor. The doctor will regularly check your condition to verify that the treatment is having the desired effect
• If you are being treated for AML, after finishing taking Rydapt together with chemotherapeutic medicines, you will receive Rydapt alone for a maximum of 12 months.
• If you are being treated for ASM, SM-AHN or MCL, you will receive Rydapt as a long-term treatment, possibly lasting for months or years. If you have questions about how long to take Rydapt, talk to your doctor or pharmacist.

If you take more Rydapt than you should
If you take more capsules than you should, or if someone else takes your medicine, contact a doctor or
go to hospital immediately, bringing the package with you, as medical treatment may be necessary.

If you forget to take Rydapt
If you forget to take Rydapt, skip the missed dose and take the next dose at the usual time.
Do not take a double dose to make up for the missed dose. Instead, wait until it is time for the next dose.

If you stop taking Rydapt
Stopping treatment with Rydapt may cause your condition to worsen. Do not
stop treatment unless your doctor tells you to do so.
If you have any doubts about using this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

Stop taking Rydapt and tell your doctor immediately if you notice any of the
followingbecause they may be signs of an allergic reaction:

• difficulty breathing or swallowing
• dizziness
• swelling of the face, lips, tongue or throat
• severe itching of the skin, with red rash or skin bumps

Some side effects in patients with AML may be serious
Tell your doctor, pharmacist or nurse immediately if you notice any of the following:

• weakness, spontaneous bleeding or bruising, frequent infections with signs such as fever, chills, sore throat or mouth sores (signs of a low level of blood cells)
• fever, cough with or without mucus, chest pain, difficulty breathing or shortness of breath (signs of non-infectious interstitial lung disease or pneumonia)
• severe shortness of breath, labored and unusually rapid breathing, dizziness, lightheadedness, confusion and extreme fatigue (signs of acute respiratory distress syndrome)
• infections, fever, low blood pressure, decreased urine output, rapid pulse, rapid breathing (signs of sepsis or neutropenic sepsis)

Other possible side effects in patients with AML
Other side effects include those listed below. If any of these side
effects become severe, tell your doctor or pharmacist.
Most side effects are mild to moderate and usually disappear after
a few weeks of treatment.

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

• infection at the catheter site
• flat, pinpoint red or purple spots under the skin (petechiae)
• trouble sleeping (insomnia)
• headache
• shortness of breath, labored breathing (dyspnea)
• abnormal electrocardiogram results that may indicate to your doctor that you have an abnormality in the electrical activity of the heart known as QT prolongation
• dizziness, lightheadedness (low blood pressure)
• nosebleed
• sore throat (laryngopharyngeal pain)
• mouth sores (stomatitis)
• nausea, vomiting
• upper abdominal pain
• hemorrhoids
• excessive sweating
• skin rash with scaling or peeling (exfoliative dermatitis)
• back pain
• joint pain (arthralgia)
• fever
• thirst, increased urine output, dark urine, dry, flushed skin (signs of high blood sugar levels, known as hyperglycemia)
• muscle weakness, drowsiness, confusion, seizures, altered consciousness (signs of high sodium levels in the blood, known as hypernatremia)
• muscle weakness, muscle spasms, abnormal heart rhythm (signs of low potassium levels in the blood, known as hypokalemia)
• bruising and bleeding (blood clotting defect)
• abnormal blood test results that may indicate to your doctor how well certain parts of the body are working: elevated alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels (indicators of liver function)

Common (may affect up to 1 in 10 people)

• upper respiratory tract infection
• nausea, vomiting, constipation, stomach discomfort, increased frequency of urination, thirst, muscle weakness and spasms (signs of high calcium levels in the blood, known as hypercalcemia)
• fainting
• uncontrollable body tremor
• headache, dizziness (high blood pressure)
• fast heartbeat (sinus tachycardia)
• fluid buildup around the heart, which, if severe, can decrease the heart's ability to pump blood (pericardial effusion)
• fluid buildup in the lungs/chest cavity, which if severe can leave you breathless (pleural effusion)
• sore throat and runny nose
• swelling of the eyelids
• discomfort in the anus and rectum
• abdominal pain, nausea, vomiting, constipation (abdominal discomfort)
• dry skin
• eye pain, blurred vision, light sensitivity (keratitis)
• neck pain
• bone pain
• limb pain
• weight gain
• blood clot in the catheter
• abnormal blood test results that may indicate to your doctor how well certain parts of the body are working: high uric acid levels

Not known (frequency cannot be estimated from available data)

• Spots or raised, painful skin sores, ranging in color from red to dark purple, appearing mainly on the arms, legs, face and neck, with fever (signs of acute febrile neutrophilic dermatosis)

Some side effects in patients with ASM, SM-AHN and MCL may be serious
Tell your doctor, pharmacist or nurse immediately if you notice any of the following:

• weakness, spontaneous bleeding or bruising, frequent infections with signs such as fever, chills, sore throat or mouth sores (signs of a low level of blood cells)
• fever, cough, difficulty breathing or painful breathing, wheezing, chest pain during breathing (signs of pneumonia)
• fever, cough with or without mucus, chest pain, difficulty breathing or shortness of breath (signs of non-infectious interstitial lung disease or pneumonia)
• infections, fever, dizziness, lightheadedness, decreased urine frequency, rapid pulse, rapid breathing (signs of sepsis or neutropenic sepsis)
• vomiting blood, black or bloody stools (signs of gastrointestinal bleeding)

Other possible side effects in patients with ASM, SM-AHN and MCL
Other side effects include those listed below. If any of these side
effects become severe, tell your doctor or pharmacist.
Most side effects are mild to moderate and usually disappear after
a few weeks of treatment.

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

• urinary tract infection
• upper respiratory tract infection
• headache
• dizziness
• shortness of breath, labored breathing (dyspnea)
• cough
• fluid buildup in the lungs/chest cavity, which if severe can leave you breathless (pleural effusion)
• abnormal electrocardiogram results that may indicate to your doctor that you have an abnormality in the electrical activity of the heart known as QT prolongation
• nosebleed
• nausea, vomiting
• diarrhea
• constipation
• swelling of the limbs (ankles and feet)
• feeling tired (fatigue)
• fever
• thirst, increased frequency of urination, dark urine, dry, flushed skin (signs of high blood sugar levels, known as hyperglycemia)
• yellowing of the skin and eyes (signs of high bilirubin levels in the blood)
• abnormal blood test results indicating possible problems with the pancreas (elevated lipase or amylase levels) and liver (elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels)

Common (may affect up to 1 in 10 people)

• uncontrollable body tremor
• cough with phlegm, chest pain, fever (bronchitis)
• cold sores due to viral infection (oral herpes)
• frequent and painful urination (cystitis)
• feeling of pressure or pain in the cheeks and forehead (sinusitis)
• painful skin rash with redness and swelling on any part of the skin (erysipelas)
• shingles (herpes zoster)
• attention disorders
• feeling of spinning or “dizziness” (vertigo)
• bruises (hematomas)
• stomach upset, indigestion
• feeling of weakness (asthenia)
• chills
• generalized swelling (edema)
• weight gain
• contusions (ecchymoses)
• falls
• dizziness, lightheadedness (low blood pressure)
• sore throat
• rapid weight gain

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any side effects not listed
in this leaflet. You can also report side effects directly through 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. How to store Rydapt

• 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 package and on the blister after EXP. The expiry date refers to the last day of that month.
• This medicine does not require any particular storage temperature. Store in the original package to protect the medicine from moisture.
• Do not use this medicine if you notice any damage to the packaging or if there are signs of tampering.
• Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Rydapt contains

• The active ingredient is midostaurin. Each soft capsule contains 25 mg of midostaurin.
• Other ingredients are: macrogol hydroxystearate (see “Rydapt contains macrogol hydroxystearate (castor oil)” in section 2), gelatin, macrogol, glycerol, anhydrous ethanol (see “Rydapt contains anhydrous ethanol (alcohol)” in section 2), corn oil mono-di-triglycerides, titanium dioxide (E171), dl-alpha-tocopherol, yellow iron oxide (E172), red iron oxide (E172), carmine (E120), hypromellose, propylene glycol, purified water.

Description of Rydapt and package contents
Rydapt 25 mg soft capsules (capsules) are oblong, light orange capsules with “PKC
NVR” in red.
The capsules are supplied in blisters and are available in packs containing 56 capsules (2 packs
of 28 capsules) or 112 capsules (4 packs of 28 capsules). Not all pack sizes
may be marketed in your country.

Marketing Authorisation Holder
Novartis Europharm Limited
Vista Building
Elm Park, Merrion Road
Dublin 4
Ireland

Manufacturer
Novartis Pharma GmbH
Roonstrasse 25
90429 Nuremberg
Germany
Novartis Farmacéutica S.A.
Gran Via de les Corts Catalanes, 764
08013 Barcelona
Spain
Novartis Pharma GmbH
Sophie-Germain-Strasse 10
90443 Nuremberg
Germany
For further information on this medicinal product, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
Novartis Pharma N.V.
Tél/Tel: +32 2 246 16 11

Lietuva
SIA Novartis Baltics Lietuvos filialas
Tel: +370 5 269 16 50

България
Novartis Bulgaria EOOD
Тел: +359 2 489 98 28

Luxembourg/Luxemburg
Novartis Pharma N.V.
Tél/Tel: +32 2 246 16 11

Česká republika
Novartis s.r.o.
Tel: +420 225 775 111

Magyarország
Novartis Hungária Kft.
Tel.: +36 1 457 65 00

Danmark
Novartis Healthcare A/S
Tlf: +45 39 16 84 00

Malta
Novartis Pharma Services Inc.
Tel: +356 2122 2872

Deutschland
Novartis Pharma GmbH
Tel: +49 911 273 0

Nederland
Novartis Pharma B.V.
Tel: +31 88 04 52 555

Eesti
SIA Novartis Baltics Eesti filiaal
Tel: +372 66 30 810

Norge
Novartis Norge AS
Tlf: +47 23 05 20 00

Ελλάδα
Novartis (Hellas) A.E.B.E.
Τηλ: +30 210 281 17 12

Österreich
Novartis Pharma GmbH
Tel: +43 1 86 6570

España
Novartis Farmacéutica, S.A.
Tel: +34 93 306 42 00

Polska
Novartis Poland Sp. z o.o.
Tel.: +48 22 375 4888

France
Novartis Pharma S.A.S.
Tél: +33 1 55 47 66 00

Portugal
Novartis Farma - Produtos Farmacêuticos, S.A.
Tel: +351 21 000 8600

Hrvatska
Novartis Hrvatska d.o.o.
Tel. +385 1 6274 220

România
Novartis Pharma Services Romania SRL
Tel: +40 21 31299 01

Ireland
Novartis Ireland Limited
Tel: +353 1 260 12 55

Slovenija
Novartis Pharma Services Inc.
Tel: +386 1 300 75 50

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Novartis Slovakia s.r.o.
Tel: +421 2 5542 5439

Italia
Novartis Farma S.p.A.
Tel: +39 02 96 54 1

Suomi/Finland
Novartis Finland Oy
Puh/Tel: +358 (0)10 6133 200

Κύπρος
Novartis Pharma Services Inc.
Τηλ: +357 22 690 690

Sverige
Novartis Sverige AB
Tel: +46 8 732 32 00

Latvija
SIA Novartis Baltics
Tel: +371 67 887 070

Other sources of information
More detailed information on this medicinal product is available on the website of the European
Medicines Agency, http://www.ema.europa.eu/ .