Label: information for the patient

Kalydeco13.4mg powder for sachet

Kalydeco 25 mg powder for sachet

Kalydeco 50 mg powder for sachet

Kalydeco 59.5mg powder for sachet

Kalydeco 75 mg powder for sachet

ivacaftor

Read this label carefully before your child starts taking this medicine, as it contains important information for your child.

• Keep this label, 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, 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 label.See section4.

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 leave 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.
• There has been an increase in liver enzymes in the blood 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 have blood tests done to check their liver function before and during treatment, especially during the first year and especially 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: a 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 they have been told that 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 any effect on vision during treatment (alone or in combination with ivacaftor/tezacaftor/elexacaftor).Your doctor may perform eye exams 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 it is unknown ifivacaftoris safe and effective in these children.

This medication should not be given in combination withivacaftor/tezacaftor/elexacaftorto children under 2years, as it is unknown ifivacaftoris safe and effective in them.

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 side 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 includefluconazol,itraconazol,ketoconazol, posaconazol, and voriconazol.
• Antibiotics(used to treat bacterial infections). These include claritromicina, eritromicina, rifabutina, rifampicina, and telitromicina.
• Antiepileptics(used to treat seizures or epileptic crises). These include carbamazepina, fenobarbital, and fenitoína.
• Herbal medications.These includeSt. John's Wort(Hypericum perforatum).
• Immunosuppressants(used after an organ transplant). These includeciclosporina,everolimus, sirolimusy tacrolimus.
• Cardiac glycosides(used to treat certain heart conditions). These include digoxina.
• Anticoagulants(used to prevent blood clots). These includewarfarina.
• Diabetes medications. These include glimepirida and glipizida.
• Antihypertensive medications.These include verapamilo.

Taking Kalydeco with food and drinks

Avoid giving your child foods or drinks that contain 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 operating machinery

Kalydeco may cause your child to feel dizzy. If your child feels dizzy, it is recommended thatthey 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 told you that your child has a certain sugar intolerance, consult with them before giving your child this medication.

Kalydeco contains less than1mmolof sodium(23mg) per dose; this 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 12-hour difference.

If your child has liver problems, it may be necessary for your child's doctor to reduce the dose of Kalydeco, 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.
• Gently shake the packet to settle the contents.
• 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. Examples of suitable soft foods or liquids 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.The 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 immediately if your child experiences any of these side effects.

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

• Upper respiratory tract infection (common cold), including 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(can 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(can 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

Unknown frequency(cannot be estimated from available data)

• Liver damage (hepatic injury)
• Increased bilirubin (liver enzyme blood 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 experiencesany typeof 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 providing more 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 appears onthe box, the container, and the envelopeafter 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 thrown down the drain or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Kalydeco Composition

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:silica anhydrous, 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 pack

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 25mg granule in blister packs, Kalydeco 50mg granule in blister packs and Kalydeco 75mg granule in blister packs:

Blister pack size of 56sheets (contains 4individual cartons with 14sheets each).

Kalydeco 59.5mg granule in blister packs:

Blister pack size of 28sheets (contains 4individual cartons with 7sheets 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 Person

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 further information about this medicinal product, please contact the local representative of the marketing authorization holder:

Last update of the summary of product characteristics:

Other sources of information

The 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 on rare diseases and orphan medicinal products.