Rydapt 25 mg soft capsules

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Rydapt 25 mg soft capsules

midostaurin

Read this entire leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you need advice or more information, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor, pharmacist, or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of this leaflet

1. What Rydapt is and what it is used for
2. What you need to know before taking 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 RyYdapt is and what it is used for

What is Rydapt

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

What Rydapt is used for

Rydapt is used to treat acute myeloid leukaemia (AML) in adults who have a defect in a gene called FLT3. Acute myeloid leukaemia is a type of cancer affecting certain white blood cells (called “myeloid” cells), in which the body produces an abnormal number of these cells.

Rydapt is also used in adults to treat aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated haematological neoplasm (SM-AHN), or mast cell leukaemia (MCL). These are disorders in which the body produces too many mast cells, a type of white blood cell. Symptoms occur when excessive numbers of mast cells infiltrate organs such as the liver, bone marrow, or spleen, releasing substances such as histamine into the bloodstream.

How Rydapt works

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

At the start of AML treatment, Rydapt is always used in combination with chemotherapy (medicines used to treat cancer).

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

2. What you need to know before taking Rydapt

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 ingredients of this medicine (listed in section 6). If you think you might be allergic, consult your doctor.

• If you are taking any of the following medicines:

• 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.

The use of these medicines should be avoided during treatment with Rydapt. Consult your doctor if you have been prescribed to start taking any of them while being treated with Rydapt.

Warnings and precautions

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

• if you have any infection
• if you have a heart disorder
• if you have lung problems or difficulty breathing
• if you have kidney problems

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

• if you have fever, sore throat, or mouth ulcers, as these could be signs of low white blood cell counts.
• if you have or your symptoms worsen, such as fever, cough with or without mucus, chest pain, difficulty breathing, or shortness of breath, as these could be signs of a lung disorder.
• if you have or notice chest pain or discomfort, malaise, dizziness, fainting, bluish discoloration of the lips or extremities, shortness of breath, or swelling in the lower legs (edema) or skin, as these could be signs of heart problems.

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

Monitoring during treatment with Rydapt

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

Children and adolescents

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

Other medicines and Rydapt

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicine. Rydapt may affect how other medicines work or may be affected by how other medicines act on Rydapt.

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

• 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.

Inform 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 blood fat levels, 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 a different one while you are being treated with Rydapt.

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

If you are unsure whether your medicine is one of those listed above, ask your doctor or pharmacist.

Pregnancy and breastfeeding

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

Rydapt may harm your baby. You must not breastfeed during treatment with Rydapt and for at least 4 months after stopping treatment.

Contraception in women

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

If you become pregnant or wish to become pregnant, inform 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

Exercise particular caution when driving or operating machinery while taking Rydapt, as it may cause dizziness and vertigo.

Rydapt contains anhydrous ethanol (alcohol)

This medicine contains 666 mg of alcohol (ethanol) in each 200 mg dose (maximum daily dose), equivalent to 14 vol.% 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 contained in this medicine does not produce any noticeable effect. However, alcohol may be harmful for people suffering from alcoholism, epilepsy, or liver problems, or if you are pregnant or breastfeeding.

Rydapt contains macrogol glycerol hydroxystearate (castor oil)

This medicine contains macrogol glycerol hydroxystearate, which may cause stomach discomfort and diarrhoea.

3. How to take Rydapt

Follow exactly the administration instructions for this medicine as given by your doctor. If in doubt, consult your doctor again.

Do not exceed the dose prescribed by your doctor.

How much Rydapt should you take

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

• Patients with AML

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

• Patients with advanced systemic mastocytosis (ASM); aggressive SM (ASM-MHA) or mast cell leukemia (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 temporarily interrupt your treatment.

How to take this medicine

• Take Rydapt every day at the same time. This will help you remember to take your medicine.
• Take Rydapt twice a day, approximately 12 hours apart (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 them to ensure correct dosing and to avoid unpleasant taste from the capsule contents.
• Patients with AML must take Rydapt with chemotherapy medicines. Therefore, it is very important that you follow your doctor's recommendations.
• If you vomit after swallowing the capsules, do not take another dose until your next scheduled dose.

How long should you take Rydapt

• Take Rydapt for as long as your doctor tells you. Your doctor will monitor you regularly to check that the treatment is having the desired effect.
• If you are being treated for AML, after completing Rydapt in combination with chemotherapy medicines, you will need to continue treatment with Rydapt alone for another 12 months.
• For ASM, ASM-MHA, or MCL, treatment with Rydapt is prolonged and may last for months or years.

If you have any questions about the duration of treatment with Rydapt, speak with 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, contact a doctor immediately or go to a hospital, and take the container with you. You may require medical treatment.

If you forget to take Rydapt

If you forget to take Rydapt, skip the missed dose and take your next dose at the usual time. Do not take a double dose to make up for a missed dose; instead, wait until your next scheduled dose.

If you stop taking Rydapt

Stopping treatment with Rydapt may cause your condition to worsen. Do not stop taking this medicine unless instructed by your doctor.

If you have any further questions about 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 everyone will experience them.

Stop taking Rydapt and speak to your doctor immediately if you notice any of the following symptoms, as they may indicate an allergic reaction:

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

Some adverse effects may be serious in patients with AML

Immediately inform your doctor, pharmacist, or nurse if you experience any of the following symptoms:

• weakness, bleeding or spontaneous bruising, frequent infections with fever, chills, sore throat, or mouth ulcers (signs of low white blood cell counts)
• fever, cough with or without mucus, chest pain, breathing difficulties, or shortness of breath (signs and symptoms consistent with interstitial lung disease or pneumonitis)
• severe shortness of breath, abnormally rapid and labored breathing, dizziness, lightheadedness, confusion, and extreme fatigue (signs of acute respiratory distress syndrome)
• infections, fever, low blood pressure, reduced urine output, rapid pulse, rapid breathing (signs of sepsis or neutropenic sepsis)

Other possible adverse effects in patients with AML

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

Most adverse effects are mild or moderate and generally resolve within a few weeks after starting treatment.

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

• infection at the catheter site
• flat red or purple spots under the skin (petechiae)
• difficulty falling asleep (insomnia)
• headache
• shortness of breath, labored breathing (dyspnea)
• abnormal electrocardiogram results that may indicate to your doctor an abnormal electrical activity in your heart, known as QT interval prolongation
• dizziness, lightheadedness (low blood pressure)
• nosebleeds
• sore throat (laryngeal pain)
• mouth ulcers (stomatitis)
• nausea, vomiting
• upper abdominal pain
• hemorrhoids (piles)
• excessive sweating
• skin rash with peeling or shedding (exfoliative dermatitis)
• back pain
• joint pain (arthralgia)
• fever
• thirst, increased urine production, dark urine, flushed and dry skin (signs of high blood sugar concentration, known as hyperglycemia)
• muscle weakness, drowsiness, confusion, seizures, altered consciousness (signs of high sodium concentration in the blood, known as hypernatremia)
• muscle weakness, muscle cramps, abnormal heart rhythm (signs of low potassium concentration in the blood, known as hypokalemia)
• bruising and bleeding (coagulation disorders)
• abnormal laboratory test results that may indicate to your doctor problems with certain organs: 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 twitching (signs of high calcium concentration in the blood, known as hypercalcemia)
• fainting
• tremors
• headache, dizziness (high blood pressure)
• rapid heartbeat (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 chest cavity; if severe, it may make breathing difficult (pleural effusion)
• sore throat and excessive nasal discharge
• eyelid swelling
• 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 laboratory test results that may indicate to your doctor problems with certain organs: elevated levels of uric acid

Some adverse effects may be serious in patients with ASM, SM-AHN, and MF

Immediately inform your doctor, pharmacist, or nurse if you notice any of the following symptoms:

• weakness, bleeding or spontaneous bruising, frequent infections with fever, chills, sore throat, or mouth ulcers (signs of low white blood cell counts)
• fever, cough, difficult or painful breathing, wheezing, chest pain when breathing (signs of pneumonia)
• fever, cough with or without mucus, chest pain, breathing difficulties, or shortness of breath (signs and symptoms consistent with interstitial lung disease or pneumonitis)
• infections, fever, dizziness, lightheadedness, reduced urine output, 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 ASM, SM-AHN, and MF

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

Most adverse effects are mild or moderate and generally resolve within a few weeks after starting 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 accumulation in the lungs or chest cavity; when significant, it may make breathing difficult (pleural effusion)
• abnormal electrocardiogram results that may indicate to your doctor an abnormal electrical activity in your heart, known as QT interval prolongation
• nosebleeds
• nausea, vomiting
• diarrhea
• constipation
• swelling of the limbs (calves, ankles)
• feeling of tiredness (fatigue)
• fever
• thirst, increased urine production, dark urine, flushed and dry skin (signs of high blood sugar concentration, known as hyperglycemia)
• yellowing of the skin and eyes (sign of elevated bilirubin levels in the blood)
• abnormal laboratory test results indicating possible pancreas problems (elevated levels of lipase or amylase) and liver problems (elevated levels of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST))

Common (may affect up to 1 in 10 people)

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

Reporting of adverse effects

If you experience any adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system detailed in Appendix V. By reporting adverse effects, you can help provide 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 expiry date stated on the carton and blister after CAD/EXP. The expiry 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 any signs of deterioration.
• Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Rydapt

• The active substance is midostaurin. Each soft capsule contains 25 mg of midostaurin.
• The other components are: macrogol glycerol hydroxystearate (see “Rydapt contains macrogol glycerol hydroxystearate (castor oil)” in section 2), gelatin, macrogol, glycerol, anhydrous ethanol (see “Rydapt contains anhydrous ethanol (alcohol)” in section 2), 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, pale orange capsules with a red "PKC NVR" imprint.

The capsules are supplied in blisters and 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

Manufacturer

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 about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Date of the most recent revision of this leaflet:

Other sources of information

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