Kalydeco 25 mg granules in sachet

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Kalydeco 13.4 mg granules in sachet

Kalydeco 25 mg granules in sachet

Kalydeco 50 mg granules in sachet

Kalydeco 59.5 mg granules in sachet

Kalydeco 75 mg granules in sachet

Ivacaftor

Read the entire leaflet carefully before your child starts taking this medicine, because it contains important information for your child.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your child's doctor or pharmacist.
• This medicine has been prescribed only for your child; do not give it to others, even if they have the same symptoms as your child, as it may harm them.
• If your child experiences any adverse effects, consult your child's doctor or pharmacist, even if such effects are not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Kalydeco is and what it is used for

Kalydeco contains the active substance ivacaftor. Ivacaftor acts on the cystic fibrosis transmembrane conductance regulator (CFTR), a protein that forms a channel on the cell surface allowing particles such as chloride to enter and leave the cell. Due to mutations in the CFTR gene (see below), chloride movement is reduced in people with cystic fibrosis (CF). Ivacaftor helps certain abnormal CFTR proteins to open more frequently, thereby improving the flow of chloride in and out of the cell.

Kalydeco granules are indicated:

• As monotherapy for the treatment of infants and children aged 4 months and older with a body weight of 5 kg to less than 25 kg with cystic fibrosis (CF) and an R117H mutation in the CFTR gene or one of the following CFTR gating mutations: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R.
• In combination with ivacaftor/tezacaftor/elexacaftor granules in sachets for patients aged 2 to 6 years who have CF and at least one F508del mutation in the CFTR gene. If you have been prescribed Kalydeco to take with ivacaftor/tezacaftor/elexacaftor, please read the ivacaftor/tezacaftor/elexacaftor package leaflet. It contains important information on how to take these two medicines.

2. What you need to know before your child takes Kalydeco

Do not give Kalydeco to your child

• if your child is allergic to ivacaftor or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your child’s doctor before your child starts taking Kalydeco.

• Talk to your child’s doctor if your child has or has previously had liver problems. Your child’s doctor may need to adjust the dose.

• Increases in liver enzymes in the blood have been observed in some people taking Kalydeco (alone or in combination with ivacaftor/tezacaftor/elexacaftor). Contact your child’s doctor immediately if your child experiences any of the following symptoms, which may indicate liver problems:

  • Pain or discomfort in the upper right side of the stomach (abdomen)
  • Yellowing of the skin or whites of the eyes
  • Loss of appetite
  • Nausea or vomiting
  • Dark urine

• Your child’s doctor will perform blood tests to monitor liver function before and during treatment, especially during the first year and particularly if previous blood tests have shown elevated liver enzymes.

• Depression (including suicidal thoughts and suicidal behaviour) has been reported in patients taking Kalydeco, mainly in a combination regimen with ivacaftor/tezacaftor/elexacaftor, typically occurring within the first three months of treatment. Contact your doctor immediately if you (or someone taking this medicine) experience any of the following symptoms: sad or changed mood, anxiety, feelings of emotional distress, or thoughts of self-harm or suicide, as these may be signs of depression.

• Talk to your child’s doctor if your child has been told they have or have previously had kidney problems.

• Kalydeco is not recommended in patients who have received an organ transplant.

• In some children and adolescents, an abnormality in the eye lens (cataract) has been observed during treatment (alone or in combination with ivacaftor/tezacaftor/elexacaftor), without any effect on vision. Your doctor may perform eye examinations before and during treatment.

• Kalydeco should only be used if your child has one of the CFTR gene mutations listed in section 1 (What Kalydeco is and what it is used for).

Children

This medicine must not be given to children under 4 months of age, as it is unknown whether ivacaftor is safe and effective in these children.

This medicine must not be given in combination with ivacaftor/tezacaftor/elexacaftor to children under 2 years of age, as it is unknown whether ivacaftor is safe and effective in these children.

Other medicines and Kalydeco

Tell your child’s doctor or pharmacist if your child is taking, has recently taken, or might need to take any other medicines. Some medicines may affect how Kalydeco works or increase the likelihood of side effects. In particular, inform your child’s doctor if your child is taking any of the following medicines. Your child’s doctor may decide to adjust the dose or increase monitoring.

• Antifungals (used to treat fungal infections). These include fluconazole, itraconazole, ketoconazole, posaconazole, and voriconazole.
• Antibiotics (used to treat bacterial infections). These include clarithromycin, erythromycin, rifabutin, rifampicin, and telithromycin.
• Medicines for epilepsy (used to treat seizures). These include carbamazepine, phenobarbital, and phenytoin.
• Herbal medicines. These include St John’s wort (Hypericum perforatum).
• Immunosuppressants (used after organ transplantation). These include cyclosporine, everolimus, sirolimus, and tacrolimus.
• Cardiac glycosides (used to treat certain heart conditions). These include digoxin.
• Anticoagulants (used to prevent blood clots). These include warfarin.
• Medicines for diabetes. These include glimepiride and glipizide.
• Medicines to lower blood pressure. These include verapamil.

Taking Kalydeco with food and drink

Do not give your child food or drinks containing grapefruit during treatment with Kalydeco, as they may increase the side effects of Kalydeco by increasing the amount of ivacaftor in your child’s body.

Driving and using machines

Kalydeco may cause dizziness in your child. If your child feels dizzy, it is recommended that they avoid riding a bicycle or performing any activity that requires full attention.

Kalydeco contains lactose and sodium

If your child’s doctor has told you that your child has an intolerance to certain sugars, talk to the doctor before your child takes this medicine.

Kalydeco contains less than 1 mmol of sodium (23 mg) per dose unit; this is essentially “sodium-free”.

3. How to take Kalydeco

Follow exactly the instructions given by your child's doctor for administering this medicine. If in doubt, consult your child's doctor again.

Your child's doctor will determine the correct dose for your child. Your child should continue taking all other medications unless your child's doctor advises otherwise.

Dosage recommendations for Kalydeco are provided in Table 1.

Table 1: Dosage recommendations

Administer the morning and evening doses of the granules to your child 12 hours apart.

• If your child has liver problems, your doctor may need to reduce the dose of Kalydeco, as your child's liver may not eliminate the medicine from the body as quickly as children with normal liver function.

  • Moderate liver problems in children aged 6 months or older: the dose may be reduced by half the dose indicated in the table above, i.e., one sachet once daily.
  • Severe liver problems in children aged 6 months or older: use is not recommended; however, your child's doctor will decide whether it is appropriate for your child to take this medicine. In such cases, the dose (as indicated in the table above) should be reduced to one sachet every two days.
  • Liver problems in children aged between 4 months and 6 months: use is not recommended; however, your child's doctor will decide whether it is appropriate for your child to take this medicine and what dose should be given.

Kalydeco must be taken by mouth.

Each sachet is for single use only.

Administration of Kalydeco to your child:

• Hold the sachet with the tear line facing upwards.
• Gently shake the sachet so that the contents settle.
• Open the sachet by breaking or cutting along the tear line.
• Mix the entire contents of one sachet with 5 mL of a soft or liquid food appropriate for the child's age. The food or liquid should be at room temperature or cooler. Examples of suitable age-appropriate soft or liquid foods include fruit or vegetable puree, yogurt, applesauce, water, milk, breast milk, infant formula, or juice.
• Once mixed, give the medicine to your child immediately. If this is not possible, administer within one hour of mixing. Make sure your child takes the entire mixture immediately.
• Just before or just after administration, give your child a meal or snack containing fat (some examples are listed below).

Meals or snacks containing fat include those prepared with butter or oils, or those containing eggs. Other foods containing fat include:

• Cheese, whole milk, whole milk dairy products, yogurt, breast milk, infant formula, chocolate
• Meat, fatty fish
• Avocado, hummus (chickpea puree), soy-based products (tofu)
• Nuts, nutritional bars, or nutritional drinks containing fat

If your child takes more Kalydeco than they should

Your child may experience adverse effects, including those listed in section 4 below. If this occurs, consult your child's doctor or pharmacist. If possible, show them the medicine and this leaflet.

If you forget to give Kalydeco to your child

Give the missed dose if less than 6 hours have passed since the time your child was supposed to take it. Otherwise, wait until the next scheduled dose is due and take it as usual. Do not give a double dose to make up for a missed dose.

If you stop your child's treatment with Kalydeco

Give Kalydeco to your child for as long as your child's doctor has recommended. Do not stop treatment unless instructed by your child's doctor. If you have any further questions about the use of this medicine, ask your child's doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Serious adverse effects

Stomach (abdominal) pain and increased liver enzymes in the blood.

Possible signs of liver problems

Increased liver enzymes in the blood are common in patients with CF and have also been reported in patients taking Kalydeco alone or in combination with ivacaftor/tezacaftor/elexacaftor.

In patients taking Kalydeco in combination with ivacaftor/tezacaftor/elexacaftor, liver damage and worsening of liver function have been reported in people with severe liver disease. Worsening liver function can be serious and may require a liver transplant.

The following may be signs of liver problems:

• Pain or discomfort in the upper right part of the stomach (abdominal area).
• Yellowing of the skin or the white part of the eyes.
• Loss of appetite.
• Nausea or vomiting.
• Dark-colored urine.

Depression

Signs of depression include a sad or altered mood, anxiety, or a feeling of emotional distress.

Contact your child’s doctor immediately if any of these adverse effects occur.

Adverse effects very common (may affect more than 1 in 10 people)

• Upper respiratory tract infection (common cold), including sore throat and nasal congestion
• Headache
• Dizziness
• Diarrhea
• Stomach or abdominal pain
• Changes in the type of bacteria in mucus
• Increased liver enzymes (signs of liver stress)
• Rash

Adverse effects common (may affect up to 1 in 10 people)

• Runny nose
• Ear pain, ear discomfort
• Ringing in the ears
• Redness inside the ears
• Inner ear disorder (sensation of dizziness or vertigo)
• Sinus problems (sinus congestion)
• Redness in the throat
• Breast lump
• Feeling of nausea
• Influenza
• Low blood sugar level (hypoglycemia)
• Abnormal breathing (shortness of breath or difficulty breathing)
• Flatulence
• Acne
• Itchy skin
• Increased creatine phosphokinase (a sign of muscle breakdown), observed in blood tests

Adverse effects uncommon (may affect up to 1 in 100 people)

• Blocked ears
• Breast inflammation
• Enlargement of the breasts in males
• Changes or pain in the nipples
• Wheezing
• Increased blood pressure

Frequency not known (cannot be estimated from available data)

• Liver damage (hepatic injury)
• Increased bilirubin (liver blood test)

Additional adverse effects in children and adolescents

Adverse effects observed in children and adolescents are similar to those observed in adults. However, increased liver enzymes in the blood are more frequent in younger children.

Reporting of adverse effects

If your child experiences any adverse effect, consult your child’s doctor or pharmacist, even if it is an effect not listed in this leaflet. You may also report them directly through the national reporting system included in Appendix V.

By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Kalydeco

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

Do not use this medicine after the expiry date stated on the carton, the case, and the sachet after CAD/EXP. The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage conditions.

After mixing, the mixture has been shown to be stable for one hour.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This helps protect the environment.

6. Contents of the pack and other information

Composition of Kalydeco

The active substance is ivacaftor.

Kalydeco 13.4 mg granules in sachet:

Each sachet contains 13.4 mg of ivacaftor.

Kalydeco 25 mg granules in sachet:

Each sachet contains 25 mg of ivacaftor.

Kalydeco 50 mg granules in sachet:

Each sachet contains 50 mg of ivacaftor.

Kalydeco 59.5 mg granules in sachet:

Each sachet contains 59.5 mg of ivacaftor.

Kalydeco 75 mg granules in sachet:

Each sachet contains 75 mg of ivacaftor.

The other components are: colloidal anhydrous silica, sodium croscarmellose, hypromellose acetate succinate, lactose monohydrate, magnesium stearate, mannitol, sucralose and sodium lauryl sulfate (E487).

See end of section 2: Kalydeco contains lactose and sodium.

Appearance of the product and contents of the pack

Kalydeco 13.4 mg granules in sachet is a white or almost white granule.

Kalydeco 25 mg granules in sachet is a white to almost white granule.

Kalydeco 50 mg granules in sachet is a white to almost white granule.

Kalydeco 59.5 mg granules in sachet is a white to almost white granule.

Kalydeco 75 mg granules in sachet is a white to almost white granule.

The granules are supplied in sachets.

Kalydeco 13.4 mg granules in sachet, Kalydeco 25 mg granules in sachet, Kalydeco 50 mg granules in sachet and Kalydeco 75 mg granules in sachet:

Pack size of 56 sachets (contains 4 individual cartons with 14 sachets each).

Kalydeco 13.4 mg granules in sachet, Kalydeco 59.5 mg granules in sachet and Kalydeco 75 mg granules in sachet:

Pack size of 28 sachets (contains 4 individual cartons with 7 sachets each).

Marketing Authorisation Holder

Vertex Pharmaceuticals (Ireland) Limited

Unit 49, Block 5, Northwood Court, Northwood Crescent

Dublin 9, D09 T665,

Ireland

Tel.: +353 (0)1 761 7299

Manufacturer

Almac Pharma Services (Ireland) Limited

Finnabair Industrial Estate

Dundalk

Co. Louth

A91 P9KD

Ireland

Almac Pharma Services Limited

Seagoe Industrial Estate

Craigavon

County Armagh

BT63 5UA

United Kingdom

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

Date of the most recent review of this leaflet:

Other sources of information

Detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu. There are also links to other websites about rare diseases and orphan medicinal products.