Package Insert: Information for the Patient

Rydapt 25 mg Soft Capsules

midostaurina

Read this entire package insert carefully before starting to take this medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you need advice or more information, consult your doctor, pharmacist, or nurse.

• This medication has been prescribed for you only, and you should not give it to others who may have the same symptoms as you, as it may harm them.

• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this package insert. See section 4.

1. What is Rydapt and for what it is used

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

3. How to take Rydapt

4. Possible adverse effects

5. Storage of Rydapt

6. Contents of the package and additional information

What is Rydapt

Rydapt contains the active ingredient midostaurina, which belongs to a group of medicines called protein kinase inhibitors.

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 type of cancer of certain white blood cells (called "myeloid" cells) by which the body produces an abnormal amount of this type of cell.

Rydapt is also used in adults to treat systemic mastocytosis aggressive (MSA), systemic mastocytosis with associated hematological neoplasia (MS-NHA), or mast cell leukemia (ML). These are alterations in which the body produces too many mast cells, which are a type of white blood cell. Symptoms appear when an excessive number of mast cells enters organs such as the liver, bone marrow, or spleen, and releases into the blood substances such as histamine.

How Rydapt works

Midostaurina blocks the action of some enzymes (kinases) in abnormal cells and stops their division and multiplication.

At the beginning of AML treatment, Rydapt is always used together with chemotherapy

(medicines used for cancer treatment).

If you have doubts about how Rydapt works or why you have been prescribed this medicine, consult your doctor, pharmacist, or nurse.

Follow exactly the instructions given by your doctor, which may differ from the general information in this leaflet.

Do not take Rydapt

• If you are allergic to midostaurin or to any of the other components of this medication (including those listed in section 6). If you think you may be allergic, consult your doctor.
• If you are taking any of the following medications:
• Medications used to treat tuberculosis, such as rifampicin;
• Medications used to treat epilepsy, such as carbamazepine or phenytoin;
• Enzalutamide, a medication used to treat prostate cancer;
• St. John's Wort (also known asHypericum perforatum), a plant-based medication used to treat depression;

These medications should be avoided during treatment with Rydapt. Consult your doctor; if you have been instructed to start taking any of them while on treatment with Rydapt;

Warnings and precautions

Consult your doctor, pharmacist, or nurse before taking Rydapt:

• If you have any infection
• If you have a heart condition
• If you have lung problems or difficulty breathing
• If you have kidney problems

Inform your doctor, pharmacist, or nurse immediately if you experience any of the following symptoms during treatment with Rydapt:

• If you have fever, sore throat, or mouth ulcers, as they may be signs of low white blood cell counts.
• If you have or worsen symptoms such as fever, cough with or without mucus, chest pain, difficulty breathing, or shortness of breath, as they may be signs of a pulmonary disorder.

If you have or notice chest pain or discomfort, dizziness, fainting, dizziness, blue discoloration of the lips or extremities, shortness of breath, or swelling of the lower legs (edema) or skin, as they may be signs of heart problems.

Your doctor may adjust your dose, or temporarily or permanently discontinue your treatment with Rydapt.

Monitoring during treatment with Rydapt

During treatment with Rydapt, blood tests will be performed at regular intervals to monitor white blood cell, red blood cell, and platelet counts, as well as electrolyte (e.g., calcium, potassium, and magnesium) concentrations in the body. Regular monitoring of heart and lung function will also be performed.

Children and adolescents

Rydapt should not be used in children or adolescents under 18 years old who are receiving chemotherapy, as it may cause severe reductions in certain types of blood cells.

Other medications and Rydapt

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication. Rydapt may affect the way other medications work or may be affected by the way other medications work on Rydapt.

During treatment with Rydapt, the following medications should be avoided:

• Medications used to treat tuberculosis, such as rifampicin;
• Medications used to treat epilepsy, such as carbamazepine or phenytoin;
• Enzalutamide, a medication used to treat prostate cancer;
• St. John's Wort (also known asHypericum perforatum), a plant-based medication used to treat depression.

Inform your doctor or pharmacist if you are taking any of the following medications:

• Some medications used to treat infections, such as ketoconazole or clarithromycin;
• Some medications used to treat HIV, such as ritonavir or efavirenz;
• Some medications used to treat depression, such as nefazodone or bupropion;
• Some medications used to control blood lipid levels, such as atorvastatin or rosuvastatin;
• Tizanidine, a medication used to relax muscles;
• Clorazepate, a medication used to treat muscle spasms.

If you are taking any of these medications, your doctor may prescribe a different medication while you are on treatment with Rydapt.

You should also inform your doctor if you are prescribed a new medication that you have not taken before during your treatment with Rydapt.

If you are unsure whether your medication is one of the medications mentioned above, ask your doctor or pharmacist.

Pregnancy and breastfeeding

Rydapt may harm your unborn baby, so it is not recommended during pregnancy. If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medication.

Rydapt may harm your baby. Do not breastfeed your baby during treatment with Rydapt and for at least 4 months after completing treatment.

Contraception in women

If you become pregnant while taking Rydapt, it may be harmful to your baby. Your doctor will ask you to take a pregnancy test before starting treatment with Rydapt to ensure you are not pregnant. You should use a contraceptive method while taking Rydapt and for at least 4 months after completing treatment. Your doctor will advise you on the most suitable contraceptive method to use.

If you become pregnant or plan to become pregnant, inform your doctor immediately.

Fertility

Rydapt may reduce fertility in men and women. You should discuss this with your doctor before starting treatment.

Driving and operating machinery

Be extra careful when driving and operating machinery while taking Rydapt, as it may cause dizziness and vertigo.

Rydapt contains anhydrous ethanol (alcohol)

This medication 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 medication is equivalent to 17 ml of beer or 7 ml of wine. The small amount of alcohol in this medication has no perceptible effect. Alcohol is harmful to people with alcoholism, epilepsy, or liver problems, or if you are pregnant or breastfeeding.

Rydapt contains macrogolglycerol hydroxystearate (castor oil)

This medication contains macrogolglycerol hydroxystearate, which may cause stomach discomfort and diarrhea.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor again.

Do not exceed the prescribed dose by your doctor.

How much Rydapt to take

Your doctor will indicate the exact number of capsules you should take.

- Patients with LMA

The usual daily dose is 50 mg (2 capsules) twice a day.

- Patients with MSA;MS_NHA or LM

The usual daily dose is 100 mg (4 capsules) twice a day.

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

How to take this medication

• Take Rydapt every day at the same time, which will help you remember to take your medicine.
• Take Rydapt twice a day at intervals of about 12 hours (for example, with breakfast and with dinner).
• Take Rydapt with food.
• Swallow the capsules whole with a glass of water. Do not open, crush, or chew the capsules to ensure correct dosing and avoid unpleasant tastes from the capsule contents.
• Patients with LMA should take Rydapt with chemotherapy medications. This is why it is very important to follow the recommendations given by your doctor.
• If you vomit after swallowing the capsules, do not take any capsules until the next dose.

How long to take Rydapt

• Take Rydapt for as long as your doctor tells you to. Your doctor will regularly monitor you to verify that the treatment is having the desired effect.
• If you are being treated for LMA, after finishing Rydapt with chemotherapy medications, you will have to continue your treatment with Rydapt alone for 12 more months.
• In the case of MSA, MS-MHA, or LM, Rydapt treatment is prolonged and may last for months or years.

If you have doubts about the duration of Rydapt treatment, 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 medication, consult immediately with a doctor or go to a hospital with the packaging. You may need to receive medical treatment.

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 compensate for the missed doses, wait until your next dose is due.

If you interrupt Rydapt treatment

Stopping Rydapt treatment may cause your condition to worsen. Do not stop taking the medication unless your doctor tells you to.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

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

Stop taking Rydapt and talk to your doctor immediately if you notice any of the following symptomssince they could be indicative of an allergic reaction:

- difficulty breathing or swallowing

- dizziness

- swelling in the face, lips, tongue, or throat

- intense itching on the skin, with a red rash or swellings

Some side effects can be serious in patients with LMA

Inform your doctor, pharmacist, or nurse immediately if you notice any of the following

symptoms:

• weakness, bleeding, or spontaneous bruises, frequent infections with fever, chills, sore throat, or mouth ulcers (signs of low white blood cell levels)
• fever, cough with or without mucus, chest pain, breathing difficulties, or shortness of breath (compatible signs and symptoms of interstitial lung disease or pneumonitis)
• severe shortness of breath, abnormal and rapid breathing, dizziness, confusion, and extreme fatigue (signs of acute respiratory distress syndrome)
• infections, fever, low blood pressure, decreased urine production, rapid pulse, and rapid breathing (signs of sepsis or neutropenic sepsis)

Other possible side effects in patients with LMA

The following are other possible side effects. If these side effects become more severe, tell your doctor or pharmacist.

Most side effects are mild or moderate and generally disappear within a few weeks of starting treatment.

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

• infection at the catheter site
• flat spots like red or purple dots under the skin (petechiae)

• difficulty falling asleep (insomnia)
• headache
• shortness of breath, abnormal breathing (dyspnea)
• abnormal electrocardiogram results that may indicate to your doctor that you have abnormal heart electrical activity, known as QT interval prolongation
• dizziness, feeling of spinning (low blood pressure)
• nasal bleeding
• sore throat (laryngitis)
• mouth ulcers (stomatitis)
• nausea, vomiting
• upper abdominal pain
• hemorrhoids (piles)
• excessive sweating
• skin rash with peeling or exfoliation (dermatitis exfoliativa)
• back pain
• joint pain (arthralgia)
• fever

• thirst, dark urine, dry skin (signs of high blood sugar, known as hyperglycemia)
• muscle weakness, somnolence, confusion, convulsions, altered consciousness (signs of high sodium levels in the blood, known as hypernatremia)
• muscle weakness, muscle cramps, abnormal heart rhythm (signs of low potassium levels in the blood, known as hypokalemia)
• bleeding and bruising (coagulation disorders)
• abnormal analytical results that may indicate to your doctor the functioning of certain parts of your body: elevated levels of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) (indicators of liver function)

Common (may affect up to 1 in 10 people)

• upper respiratory tract infection
• nausea, vomiting, constipation, abdominal pain, frequent urination, thirst, muscle weakness, and muscle contractions (signs of high calcium levels in the blood, known as hypercalcemia)
• syncope
• shivering
• headache, dizziness (high blood pressure)
• rapid heartbeats (sinus tachycardia)
• fluid accumulation in the sac surrounding the heart; if severe, it may reduce the heart's ability to pump blood (pericardial effusion)
• fluid accumulation in the lungs or thoracic cavity; if severe, it may make breathing difficult (pleural effusion)
• sore throat and abundant nasal discharge
• swelling of the eyelids
• anorectal discomfort
• abdominal pain, nausea, vomiting, constipation (abdominal discomfort)
• dry skin
• eye pain, blurred vision, light intolerance (keratitis)
• neck pain
• bone pain
• extremity pain
• weight gain
• blood clots in the catheter
• abnormal analytical results that may indicate to your doctor the functioning of certain parts of your body: elevated levels of uric acid

Some side effects can be serious in patients with MSA, MS-NHA, and LM

Inform your doctor, pharmacist, or nurse immediately if you notice any of the following symptoms:

• weakness, bleeding, or spontaneous bruises, frequent infections with fever, chills, sore throat, or mouth ulcers (signs of low white blood cell levels)
• fever, cough, breathing difficulties, or chest pain (compatible signs and symptoms of pneumonia)
• fever, cough with or without mucus, chest pain, breathing difficulties, or shortness of breath (compatible signs and symptoms of interstitial lung disease or pneumonitis)
• infections, fever, dizziness, confusion, decreased urine production, rapid pulse, and rapid breathing (signs of sepsis or neutropenic sepsis)
• vomiting blood, black or bloody stools (signs of gastrointestinal hemorrhage)

Other possible side effects in patients with MSA, MS-NHA, and LM

The following are other possible side effects. If these side effects become more severe, tell your doctor or pharmacist.

Most side effects are mild or moderate and generally disappear within a few weeks of starting treatment.

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

• urinary tract infection
• upper respiratory tract infection
• headache
• dizziness
• shortness of breath, abnormal breathing (dyspnea)
• cough
• fluid accumulation in the lungs or thoracic cavity; when severe, it may make breathing difficult (pleural effusion)
• abnormal electrocardiogram results that may indicate to your doctor that you have abnormal heart electrical activity, known as QT interval prolongation
• nasal bleeding
• nausea, vomiting
• diarrhea
• constipation
• swelling of the extremities (ankles, feet)
• sensation of fatigue (fatigue)
• fever

• thirst, dark urine, dry skin (signs of high blood sugar, known as hyperglycemia)
• yellow skin and eyes (signs of elevated bilirubin levels in the blood)
• abnormal analytical results that may indicate to your doctor the functioning of certain parts of your body: elevated levels of lipases or amylase (indicating possible pancreatic problems) and elevated levels of alanine aminotransferase (ALT) /or aspartate aminotransferase (AST) (indicating possible liver problems)

Common (may affect up to 1 in 10 people)

• shivering
• cough with phlegm, chest pain, fever (bronchitis)
• fever blisters in the mouth due to a viral infection (herpes labialis)
• painful urination and frequent urination (cystitis)
• sensation of pressure or pain in the cheeks and forehead (sinusitis)
• red, inflamed, and painful rash in any area of the skin (erysipela)
• shingles (herpes zoster)
• attention disorders
• dizziness with a sensation of spinning (vertigo)
• bruise (hematoma)
• stomach discomfort, indigestion
• weakness (asthenia)
• chills
• generalized swelling (edema)
• weight gain
• bruise (cardenales)
• falls
• dizziness, confusion (low blood pressure)
• sore throat
• rapid weight gain

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 prospectus. You can also report them directly through the national 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 box and on the blister pack after CAD/EXP. The expiration date is the last day of the month indicated.
• This medication does not require any special temperature for conservation.Store in theoriginal packaging to protect it from moisture.
• Do not use this medication if you observe any damage to the packaging or if there is any sign of deterioration.
• Medications should not be disposed of through drains or in the trash. Ask your pharmacisthow to dispose of the containers and medications that you no longer need. This will help to protect the environment.

Composition of Rydapt

• The active ingredient is midostaurin. Each soft capsule contains 25mg midostaurin.
• The other components are: macrogolglycerol hydroxystearate (see “Rydapt contains macrogolglycerol hydroxystearate (castor oil derivative)” in section2),gelatin, macrogol, glycerol, anhydrous ethanol (see “Rydapt contains anhydrous ethanol (alcohol)” in section2), mono-di-triglycerides of corn oil, titanium dioxide (E171), all-‑rac‑alpha‑tocopherol, yellow iron oxide (E172), red iron oxide (E172), carmine acid (E120), hypromellose, propylene glycol, and purified water.

Appearance of the product and contents of the pack

Rydapt 25 mg soft capsules (capsules) are oblong capsules, pale orange in color with a red

“PKC NVR” imprint.

The capsules come in blisters and are available in packs containing 112 capsules (4 packs of

28 capsules).

Marketing Authorization Holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

Responsible Person

Novartis Pharma GmbH Roonstrasse 25

90429 Nuremberg

Germany

Novartis Pharma GmbH

Sophie-Germain-Strasse 10

90443 Nürnberg

Germany

Novartis Farmacéutica S.A.

Gran Via de les Corts Catalanes, 764

08013 Barcelona

Spain

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

Last review date of this leaflet:

Other sources of information

The detailed information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu