Kalydeco 25 mg granulado en sobre

Patient Information Leaflet: Information for the Patient

Kalydeco 13.4 mg Powder for Suspension

Kalydeco 25 mg Powder for Suspension

Kalydeco 50 mg Powder for Suspension

Kalydeco 59.5 mg Powder for Suspension

Kalydeco 75 mg Powder for Suspension

Ivacaftor

Read the entire patient information leaflet carefully before your child starts taking this medicine, as 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 for your child only, and should not be given to other people even if they have the same symptoms as your child, as it may harm them.
• If your child experiences any side effects, consult your child's doctor or pharmacist, even if they are not listed in this leaflet.See section 4.

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

Kalydeco granule is indicated:

• As monotherapy for the treatment of babies and children 4 months of age or older with a weight of 5 kg to less than 25 kg with cystic fibrosis (CF) and a mutationR117Hin the CFTR gene or one of the following channel-opening mutations in the CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N or S549R.
• In combination with ivacaftor/tezacaftor/elexacaftor granule in a packet for patients 2 to 6 years of age who have CF, with at least one F508del mutation in the CFTR gene.If you have been prescribed Kalydeco to take with ivacaftor/tezacaftor/elexacaftor, read the prospectus for ivacaftor/tezacaftor/elexacaftor. It contains important information on how to take these two medications.

Do not administer Kalydeco to your child

• if your child is allergic to ivacaftor or any of the other components of this medication (listed in section6).

Warnings and precautions

Consult your child's doctor before starting Kalydeco.

• Consult your child's doctor if your child has or has had liver problems. The doctor may need to adjust your child's dose.
• Increased liver enzymes in the blood have been observed in some people taking Kalydeco (alone or in combination with ivacaftor/tezacaftor/elexacaftor). Consult your child's doctor immediately if your child experiences any of the following symptoms, which may indicate liver problems:
• Abdominal pain or discomfort in the upper right side of the 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 check liver function before and during treatment, especially during the first year and if previous blood tests indicated elevated liver enzymes.

• Depression (including suicidal thoughts and behaviors) has been reported in patients taking Kalydeco, primarily in combination with ivacaftor/tezacaftor/elexacaftor, which usually occurs within the first three months of treatment. Consult your doctor immediately if you (or someone taking this medication) experience any of the following symptoms: sad or altered mood, anxiety, emotional discomfort, or thoughts of self-harm or suicide, which may be signs of depression.

• Consult your child's doctor if your child has or has had kidney problems.

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

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

• Kalydeco should only be used if your child has one of the mutations in the CFTR gene listed in section1 (What is Kalydeco and what is it used for).

Children

This medication should not be given to children under 4 months, as the safety and efficacy of ivacaftor in these children are unknown.

This medication should not be given in combination with ivacaftor/tezacaftor/elexacaftor to children under 2 years, as the safety and efficacy of ivacaftor in these children are unknown.

Other medications and Kalydeco

Inform your child's doctor or pharmacist if your child is taking, has taken recently, or may need to take any other medication. Some medications may affect how Kalydeco works or increase the likelihood of adverse effects. Specifically, inform your child's doctor if your child is taking any of the following medications. The doctor may decide to adjust the dose or schedule more check-ups.

• 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, rifampin, and telithromycin.
• Antiepileptic medications(used to treat seizures or epileptic crises). These include carbamazepine, phenobarbital, and phenytoin.
• Herbal medications.These include St. John's Wort (Hypericum perforatum).
• Immunosuppressants(used after an organ transplant). 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.
• Diabetes medications. These include glimepiride and glipizide.
• Antihypertensive medications.These include verapamil.

Taking Kalydeco with food and drinks

Avoid giving your child foods or drinks containing grapefruit during Kalydeco treatment, as they may increase the adverse effects of Kalydeco by increasing the amount of ivacaftor in your child's body.

Driving and operating machinery

Kalydeco may cause dizziness in your child. If your child feels dizzy, it is recommended that they not ride a bike or engage in any activity that requires their full attention.

Kalydeco contains lactose and sodium.

If your child's doctor has indicated that your child has a certain sugar intolerance, consult with them before your child takes this medication.

Kalydeco contains less than1mmolof sodium (23mg) per dose; it is essentially "sodium-free."

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

Your child's doctor will determine the correct dose for your child. Your child should continue using all other medications, unless your child's doctor advises them to stop taking one.

The dosing recommendations for Kalydeco are provided in Table 1.

Table1: Dosing Recommendations

Administer the morning granule dose and the evening granule dose to your child with a 12hour interval.

If your child has liver problems, it may be necessary for your child's doctor to reduce the Kalydeco dose, as your child's liver will not eliminate the medication from their body as quickly as in children with normal liver function.

• Moderate liver problems in children 6 months or older:the dose can be reduced to half of the dose indicated in the table above, i.e., one packet per day.
• Severe liver problems in children 6 months or older:use is not recommended, but your child's doctor will decide if it is appropriate for your child to use this medication, in which case the dose (as indicated in the table above)should be reduced to one packet every two days.
• Liver problems in children between 4months and 6months old:use is not recommended, but your child's doctor will decide if it is appropriate for your child to use this medication and what dose they should receive.

Kalydeco should be taken orally.

Each packet is for single use only.

Administration of Kalydeco to your child:

• Hold the packet of granules with the line for cutting upwards.
• Agitate the packet gently so that the contents settle.
• Open the packet by breaking or cutting along the line for cutting.
• Mix the entire contents of one packet with 5ml of a suitable soft food or liquid for the child's age. The food or liquid should be at room temperature or cooler. Some examples of suitable soft foods or liquids for the child's age include fruit or vegetable puree, yogurt, apple sauce, water, milk, breast milk, formula milk, or juice.
• Once mixed, give the medication to your child immediately. If this is not possible, give it within the next hour of mixing. Ensure that the entire mixture is taken immediately.
• Just before or just after administration, give your child a food or snack containing fats (some examples are provided below).

Foods or snacks containing fats include those prepared with butter or oils or those containing eggs. Other foods containing fats are:

• Dairy products, whole milk, whole milk products, yogurt, breast milk, formula milk, chocolate
• Meat, blue fish
• Avocado, hummus (chickpea puree), soy-based products (tofu)
• Nuts, bars, or nutritional beverages containing fats

If your child takes more Kalydeco than they should

Your child may experience adverse effects, including those listed in section4 below. If so, consult your child's doctor or pharmacist. If possible, show them the medication and this leaflet.

If you forgot to give Kalydeco to your child

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

If you interrupt treatment with Kalydeco for your child

Administer Kalydeco to your child for the entire time recommended by your child's doctor. Do not stop treatment unless your child's doctor advises you to. If you have any other questions about using this medication, ask your child's doctor or pharmacist.

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

Severe side effects

Abdominal pain andincreased liver enzymes in the blood.

Possible signs of liver problems

The increase in liver enzymes in the blood is common in patients with FQ and has 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 functionhave been reported in people with severe liver disease. Worsening of liver function can be severe and may require a 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

The signs of depression include a sad or altered mood, anxiety, or emotional discomfort.

Inform your child's doctor immediatelyif you experience any of these side effects.

Side effectsvery common(may affect more than1 in 10people)

• Upper respiratory tract infection (common cold), which includes sore throat and nasal congestion
• Headache
• Dizziness
• Diarrhea
• Abdominal pain or discomfort
• Changes in the type of bacteria in mucus
• Increased liver enzymes (signs of liver stress)
• Skin rash

Side effectscommon(may affect up to1 in 10people)

• Nasal mucosity
• Ear pain, ear discomfort
• Tinnitus (ringing in the ears)
• Ear redness
• Inner ear disorder (feeling of dizziness or spinning)
• Paranasal sinus problems (nasal congestion)
• Enlargement of the breasts
• Nausea
• Influenza
• Low blood sugar (hypoglycemia)
• Abnormal breathing (shortness of breath or difficulty breathing)
• Flatulence (gas)
• Acne (pimples)
• Itching skin
• Increased creatine phosphokinase (sign of muscle breakdown), observed in blood tests

Side effectsuncommon(may affect up to1 in 100people)

• Eustachian tube blockage
• Mastitis (inflammation of the breast)
• Male breast enlargement
• 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 enzyme test)

Additional side effects in children and adolescents

The side effects observed in children and adolescents are similar to those observed in adults. However, increased liver enzymes in the blood are more common in young children.

Reporting side effects

If your child experiences any type of side effect, consult your child's doctor or pharmacist, even if it is a side effect that does not appear in this leaflet. You can also report them directly through thenational notification system included in theAppendix V.

By reporting side effects, you can contribute to providingmore information about 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 appearson the box, the container, and the overwrap after CAD/EXP. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Once mixed, the mixture has been shown to be stable for one hour.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. By doing so, you will help protect the environment.

Kalydeco Composition

The active ingredient is ivacaftor.

Kalydeco 13.4mg granule in blister pack:

Each blister pack contains 13.4mg of ivacaftor.

Kalydeco 25mg granule in blister pack:

Each blister pack contains 25mg of ivacaftor.

Kalydeco 50mg granule in blister pack:

Each blister pack contains 50mg of ivacaftor.

Kalydeco 59.5mg granule in blister pack:

Each blister pack contains 59.5mg of ivacaftor.

Kalydeco 75mg granule in blister pack:

Each blister pack contains 75mg of ivacaftor.

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

See the end of section2: Kalydeco contains lactose and sodium.

Appearance of the product and contents of the package

Kalydeco 13.4 mg granule in blister pack is a white or off-white granule.

Kalydeco 25mg granule in blister pack is a white to off-white granule.

Kalydeco 50mg granule in blister pack is a white to off-white granule.

Kalydeco 59.5mg granule in blister pack is a white to off-white granule.

Kalydeco 75mg granule in blister pack is a white to off-white granule.

The granule is supplied in blister packs.

Kalydeco 13.4 mg granule in blister pack, Kalydeco 25 mg granule in blister pack, Kalydeco 50 mg granule in blister pack, and Kalydeco 75 mg granule in blister pack:

Package size of 56 blister packs (contains 4 individual cases with 14 blister packs each).

Kalydeco 13.4 mg granule in blister pack, Kalydeco 59.5 mg granule in blister pack, and Kalydeco 75 mg granule in blister pack:

Package size of 28 blister packs (contains 4 individual cases with 7 blister packs each).

Marketing Authorization Holder

Vertex Pharmaceuticals (Ireland) Limited

Unit 49, Block 5, Northwood Court,Northwood Crescent

Dublin 9, D09 T665,

Ireland

Tel.: +353 (0)1 761 7299

Responsible for Manufacturing

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

UK

For more information about this medicine, please contact the local representative of the marketing authorization holder:

Last review date of this leaflet:

Other sources of information

Detailed information about this medicine 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 medicines.