RYDAPT 25 mg SOFT CAPSULES

Your doctor may adjust your dose, or interrupt your treatment with Rydapt for a while or stop it altogether.

Monitoring during treatment with Rydapt

During treatment with Rydapt, you will have regular blood tests to monitor your blood cell counts (white blood cells, red blood cells, and platelets) and the levels of electrolytes (e.g., calcium, potassium, and magnesium) in your body. Your heart and lung function will also be regularly monitored.

Children and adolescents

Rydapt should not be used in children and adolescents under 18 years of age who are receiving chemotherapy, as it may cause severe reductions in certain 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. Rydapt may affect the way other medicines work or may be affected by the way other medicines work.

The following medicines should be avoided during treatment with Rydapt:

• medicines used to treat tuberculosis, such as rifampicin;
• medicines used to treat 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 to treat depression.

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

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

If you are taking any of these medicines, your doctor may prescribe a different one while you are being treated with Rydapt.

You should also tell your doctor if you are prescribed a new medicine that you were not taking before during treatment with Rydapt.

If you are not sure if your medicine is one of the medicines 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, ask your doctor for advice before taking this medicine.

Rydapt may harm your baby. You should not breastfeed while taking Rydapt and for at least 4 months after finishing treatment.

Contraception in women

If you become pregnant while taking Rydapt, it may harm your baby. Your doctor will ask you to have a pregnancy test before starting treatment with Rydapt to make sure you are not pregnant. You must use a contraceptive method while taking Rydapt and for at least 4 months after finishing treatment. Your doctor will advise you on the most suitable contraceptive method to use.

If you become pregnant or want to become pregnant, tell your doctor immediately.

Fertility

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

Driving and using machines

Be careful while driving or using machines while taking Rydapt, as it may cause dizziness and vertigo.

Rydapt contains ethanol (alcohol)

This medicine contains 666 mg of alcohol (ethanol) in each 200 mg dose (maximum daily dose), which is equivalent to 14% v/v 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 does not have any noticeable effect. Alcohol is harmful for individuals with alcoholism, epilepsy, or liver disease, or if you are pregnant or breastfeeding.

Rydapt contains macrogolglycerol hydroxystearate (castor oil)

This medicine contains macrogolglycerol hydroxystearate, which may cause stomach upset and diarrhea.

3. How to take Rydapt

Follow exactly the administration instructions given to you by your doctor. If you are unsure, ask your doctor again.

Do not exceed the dose prescribed by your doctor.

How much Rydapt to take

Your doctor will tell you the exact number of capsules to take.

• Patient with AML

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

• Patient with ASM, SM-AHN, or MCL

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

Depending on how you respond to Rydapt, your doctor may reduce your dose or interrupt your treatment for a while.

How to take this medicine

• Take Rydapt every day at the same time to help you remember to take your medicine.
• Take Rydapt twice a day, approximately 12 hours apart (e.g., with breakfast and dinner).
• Take Rydapt with food.
• Swallow the capsules whole with a glass of water. Do not open, crush, or chew them to ensure the correct dose and avoid unpleasant tastes from the capsule contents.
• Patient with AML should take Rydapt with chemotherapy. It is therefore very important that you follow the recommendations given by your doctor.
• If you vomit after swallowing the capsules, do not take another capsule until the next dose.

How long to take Rydapt

• Take Rydapt for as long as your doctor tells you. Your doctor will regularly monitor you to check that the treatment is working.
• If you are being treated for AML, after finishing treatment with Rydapt and chemotherapy, you will need to continue treatment with Rydapt alone for a further 12 months.
• In the case of ASM, SM-AHN, or MCL, treatment with Rydapt is long-term and may last for months or years.

If you have any doubts about the duration of treatment with 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 a hospital immediately, taking the pack with you. You may need 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 make up for a missed dose, just wait until the next dose is due.

If you stop taking Rydapt

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

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Stop taking Rydapt and talk to your doctor immediately if you notice any of the following symptomsas it 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 swelling

Some adverse effects can be serious in patients with LMA

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

symptoms:

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

Other possible adverse effects in patients with LMA

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

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

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

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

• difficulty sleeping (insomnia)
• headache
• shortness of breath, tired 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 fainting (low blood pressure)
• nasal bleeding
• sore throat (pharyngeal pain)
• mouth ulcers (stomatitis)
• nausea, vomiting
• upper abdominal pain
• hemorrhoids (piles)
• excessive sweating
• skin rash with peeling or flaking (exfoliative dermatitis)
• back pain
• joint pain (arthralgia)
• fever

• thirst, high urine production, dark urine, reddened and dry 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 cramps, abnormal heart rhythm (signs of low potassium levels in the blood, known as hypokalemia)
• bruising and bleeding (coagulation disorders)
• abnormal laboratory results that may indicate to your doctor problems with 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, stomach pain, frequent urination, thirst, muscle weakness, and muscle contractions (signs of high calcium levels in the blood, known as hypercalcemia)
• fainting
• tremors
• headache, dizziness (high blood pressure)
• rapid heart rate (sinus tachycardia)
• fluid accumulation in the sac surrounding the heart; if severe, it can reduce the heart's ability to pump blood (pericardial effusion)
• fluid accumulation in the lungs or thoracic cavity; if severe, it can make breathing difficult (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 intolerance (keratitis)
• neck pain
• bone pain
• pain in the limbs
• weight gain
• blood clots in the catheter
• abnormal laboratory results that may indicate to your doctor problems with certain parts of your body: elevated levels of uric acid

Some adverse 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, spontaneous bleeding or bruising, frequent infections with fever, chills, sore throat, or mouth ulcers (sign of low white blood cell count)
• fever, cough, difficulty breathing or painful breathing, wheezing, chest pain (signs of pneumonia)
• fever, cough with or without mucus, chest pain, breathing problems, or shortness of breath (signs and symptoms compatible with interstitial lung disease or pneumonitis)
• infections, fever, dizziness, drowsiness, decreased urine production, rapid pulse, rapid breathing (signs of sepsis or neutropenic sepsis)
• vomiting blood, black or bloody stools (signs of gastrointestinal bleeding)

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

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

Most adverse effects are mild or moderate and usually 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, tired breathing (dyspnea)
• cough
• fluid accumulation in the lungs or thoracic cavity; if severe, it can 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 limbs (calf, ankle)
• feeling of fatigue (fatigue)
• fever

• thirst, high urine production, dark urine, reddened and dry skin (signs of high blood sugar levels, known as hyperglycemia)
• yellowing of the skin and eyes (sign of elevated bilirubin levels in the blood)
• abnormal laboratory results that indicate possible problems with the pancreas (elevated levels of lipase or amylase) and liver (elevated levels of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST))

Common (may affect up to 1 in 10 people)

• tremors
• cough with mucus, chest pain, fever (bronchitis)
• mouth sores due to a viral infection (cold sore)
• painful urination and frequent urination (cystitis)
• feeling of pressure or pain in the cheeks and forehead (sinusitis)
• red, inflamed, and painful rash on any area of the skin (erysipelas)
• shingles (herpes zoster)
• attention disorders
• dizziness with a feeling of spinning (vertigo)
• bruising (hematoma)
• stomach discomfort, indigestion
• weakness (asthenia)
• chills
• generalized swelling (edema)
• weight gain
• bruising (contusion)
• falls
• dizziness, drowsiness (low blood pressure)
• sore throat
• rapid weight gain

Reporting of 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 leaflet. 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 Rydapt

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiration date that appears on the box and on the blister after CAD/EXP. The expiration date is the last day of the month indicated.
• This medicine does not require any special storage temperature. Store in the original packaging to protect it from moisture.
• Do not use this medicine if you notice any damage to the packaging or if there are any signs of deterioration.
• 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 Rydapt

• The active ingredient is midostaurin. Each soft capsule contains 25 mg of midostaurin.
• The other ingredients are: macrogolglycerol hydroxystearate (see "Rydapt contains macrogolglycerol 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), all-rac-alpha-tocopherol, yellow iron oxide (E172), red iron oxide (E172), carmine (E120), hypromellose, propylene glycol, and purified water.

Appearance of the Product and Package Contents

Rydapt 25 mg soft capsules (capsules) are oblong, pale orange capsules with red printing

"PKC NVR".

The capsules come in blisters and are available in packages containing 112 capsules (4 packages of 28 capsules).

Marketing Authorization Holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

Manufacturer

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:

Date of Last Revision of this Leaflet:

Other Sources of Information

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