Kalydeco

Package leaflet: Information for the patient

Kalydeco 75 mg film-coated tablets, 150 mg film-coated tablets

ivacaftor
Please read this entire leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Kalydeco is and what it is used for
2. What you need to know before taking 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, which allows ions 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 defective CFTR proteins to open more frequently, thereby improving the movement of chloride in and out of the cell.

Kalydeco tablets are indicated:

• As monotherapy in patients aged 6 years and older and weighing at least 25 kg with cystic fibrosis (CF) who have the R117H CFTR mutation or one of the following gating mutations in the CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R.
• In combination with tezacaftor/ivacaftor tablets in patients aged 6 years and older with CF who have two F508del mutations in the CFTR gene (homozygous for the F508del mutation), or who have one F508del mutation and certain other specific second mutations that result in reduced quantity and/or function of the CFTR protein (heterozygous for the F508del mutation with a residual function (RF) mutation). If you have been prescribed Kalydeco in combination with tezacaftor/ivacaftor, please read the package leaflet for that medicine, as it contains important information on how to take these two medicines.
• In combination with ivacaftor/tezacaftor/elexacaftor tablets in patients aged 6 years and older with CF who have at least one mutation in the CFTR gene that responds to Kalydeco in combination with ivacaftor/tezacaftor/elexacaftor. If you have been prescribed Kalydeco in combination with ivacaftor/tezacaftor/elexacaftor, please read the package leaflet for that medicine, as it contains important information on how to take these two medicines.

2. What you need to know before taking Kalydeco

Do not take Kalydeco

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

Warnings and precautions
Talk to your doctor or pharmacist before taking Kalydeco.

• Talk to your doctor if you have or have previously had liver problems, as your dose may need to be adjusted.
• Increases in liver enzymes in the blood have been observed in some people treated with Kalydeco (alone or in combination with tezacaftor/ivacaftor or ivacaftor/tezacaftor/elexacaftor). Inform your doctor immediately if you experience any of the following symptoms, which may be signs of liver problems:
• Pain or discomfort in the upper right abdominal area
• Yellowing of the skin or whites of the eyes
• Loss of appetite
• Nausea or vomiting
• Dark urine
• Your doctor will order blood tests to monitor liver function before starting treatment and during treatment, particularly during the first year, and especially if previous blood tests have shown elevated liver enzyme levels.
• Depression (including suicidal thoughts and behaviors) has been reported in patients taking Kalydeco, mainly in combination regimens with tezacaftor/ivacaftor or ivacaftor/tezacaftor/elexacaftor, usually within the first three months of treatment. Contact your doctor immediately if you (or someone taking this medicine) experience any of the following symptoms: low or changed mood, anxiety, feelings of emotional distress, or thoughts of self-harm or suicide, as these may be signs of depression.
• Inform your doctor if you have or have previously had kidney problems.
• If you have two Class I mutations (mutations known not to produce the CFTR protein), you should not take Kalydeco, as a response to this medicine is not expected.
• Kalydeco is not recommended for patients who have undergone organ transplantation.
• Consult your doctor if you are using a hormonal contraceptive, e.g., if you are a woman taking oral contraceptives. This may increase the likelihood of developing a rash during treatment with Kalydeco in combination with ivacaftor/tezacaftor/elexacaftor.
• Lens abnormalities (cataracts), without effect on vision, have been observed in some children and adolescents treated with Kalydeco (alone or in combination with tezacaftor/ivacaftor or ivacaftor/tezacaftor/elexacaftor). Your doctor may perform eye examinations before and during treatment.
• Kalydeco should only be used if you have one of the CFTR gene mutations listed in section 1 (What Kalydeco is and what it is used for).

Children and adolescents
Do not give this medicine to children under 1 month of age, as it is not known whether ivacaftor is safe and effective in this age group.
Do not give this medicine in combination with tezacaftor/ivacaftor to children under 6 years of age, or in combination with ivacaftor/tezacaftor/elexacaftor to children under 2 years of age, as safety and effectiveness have not been established in these age groups.

Other medicines and Kalydeco
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Some medicines may affect the action of Kalydeco or increase the likelihood of side effects. In particular, inform your doctor if you are taking any of the following medicines. Your doctor may decide to adjust your dose or perform additional monitoring.

• Antifungal medicines (used to treat fungal infections). These include fluconazole, itraconazole, ketoconazole, posaconazole, and voriconazole.
• Antibiotic medicines (used to treat bacterial infections). These include clarithromycin, erythromycin, rifabutin, rifampicin, and telithromycin.
• Antiepileptic medicines (used to treat seizures or epileptic attacks). 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.
• Anticoagulant medicines (used to prevent blood clots). These include warfarin.
• Medicines for diabetes. These include glimepiride and glipizide.
• Medicines to lower blood pressure. These include verapamil.

Kalydeco with food and drinks
Avoid food or drinks containing grapefruit during treatment, as these may increase side effects of Kalydeco by increasing the amount of ivacaftor in the body.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor before taking this medicine. It may be preferable to avoid using Kalydeco during pregnancy, if possible, and your doctor will help you decide what is best for you and your baby.
Ivacaftor is excreted in breast milk. If you plan to breastfeed, consult your doctor before taking Kalydeco. Your doctor will decide whether to recommend discontinuing breastfeeding or discontinuing ivacaftor therapy, taking into account the benefits of breastfeeding for the child and the benefits of treatment for you.

Driving and using machines
Kalydeco may cause dizziness. If you experience dizziness, do not drive, ride a bicycle, or operate machinery.

Kalydeco contains lactose and sodium
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.
Kalydeco contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially 'sodium-free'.

3. How to take Kalydeco

Take this medicine exactly as instructed by your doctor. If you have any doubts, consult your
doctor.
Your doctor will decide the appropriate medicine and dose for you.
Dosage recommendations for Kalydeco are provided in Table 1.
Table 1: Dosage recommendations

Take the morning and evening doses approximately 12 hours apart with fatty foods.
You must continue to use all other medicines you are currently taking, unless your doctor tells you
otherwise.
If you have moderate or severe liver problems, your doctor may reduce the dose of the tablets, because your liver
will not eliminate the medicine as quickly as in people with normal liver function.
This medicine is for oral use.
Swallow the tablet whole. Do not split, chew, or dissolve the tablets. Take Kalydeco tablets with foods that contain fat.
Meals or snacks containing fat include those prepared with butter or oil, or those containing eggs.
Other foods containing fat are:

• cheeses, whole milk, dairy products made from whole milk, yoghurt, chocolate
• meat, oily fish
• avocado, hummus, soy-based products (tofu)
• dried nuts, protein bars or protein drinks containing fat

If you take more Kalydeco than you should
Adverse effects may occur, including those listed in section 4 below. In this case, contact your
doctor or pharmacist for advice. If possible, keep the medicine and this package leaflet with you.
If you forget to take Kalydeco
Take the missed dose if less than 6 hours have passed since the scheduled time. Otherwise, wait until the next
regularly scheduled dose. Do not take a double dose to make up for the missed dose.
If you stop taking Kalydeco
Take Kalydeco for the entire period recommended by your doctor. Do not stop treatment unless instructed by your doctor.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Serious side effects

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

Possible signs of liver problems

An increase in liver enzymes in the blood is common in patients with CF and has also been reported in patients taking Kalydeco alone or in combination with tezacaftor/ivacaftor or ivacaftor/tezacaftor/elexacaftor.

Liver damage and worsening of liver function have been reported in patients treated with Kalydeco in combination with ivacaftor/tezacaftor/elexacaftor, in people with severe liver disease. Worsening of liver function can be severe and may require liver transplantation.

The following symptoms may be signs of liver problems:

• pain or discomfort in the upper right part of the stomach (abdomen)
• yellowing of the skin or whites of the eyes
• loss of appetite
• nausea or vomiting
• dark urine

Depression

Signs include sad or changed mood, anxiety, feelings of emotional discomfort.

Contact your doctor immediately if you experience any of these symptoms.

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

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

Common side effects (may affect up to 1 in 10 people)

• Runny nose
• Earache, ear disorder
• Ringing in the ears (tinnitus)
• Redness inside the ear
• Inner ear disorder (feeling of vertigo or spinning sensation)
• Sinus problems (sinus congestion)
• Redness in the throat
• Breast mass
• Nausea
• Influenza
• Low blood sugar levels (hypoglycaemia)
• Abnormal breathing (shortness of breath or difficulty breathing)
• Intestinal gas (flatulence)
• Acne
• Itchy skin
• Increased creatine phosphokinase (a sign of muscle breakdown) observed in blood tests

Uncommon side effects (may affect up to 1 in 100 people)

• Ear congestion
• Inflammation of the breast
• Breast enlargement in males
• Nipple changes or pain
• Wheezing
• Increased blood pressure

Not known (frequency cannot be estimated from the available data)

• Liver damage (liver injury)
• Increased bilirubin levels (a blood test for liver function)

Additional side effects in children and adolescents

The side effects observed in children and adolescents are similar to those seen in adults. However, increases in liver enzymes in the blood occur more frequently in younger children.

Reporting of side effects

If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system referred to in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store 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, blister pack, and bottle label after Scad./EXP. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Kalydeco contains

• The active substance is ivacaftor.

Kalydeco 75 mg film-coated tablets
Each film-coated tablet contains 75 mg of ivacaftor.
Kalydeco 150 mg film-coated tablets
Each film-coated tablet contains 150 mg of ivacaftor.
The other components are:

• Tablet core: microcrystalline cellulose, monohydrate lactose, hypromellose acetate succinate, sodium croscarmellose, sodium lauryl sulfate (E487), colloidal anhydrous silica and magnesium stearate.
• Film coating of the tablet: polyvinyl alcohol, titanium dioxide (E171), macrogol (PEG 3350), talc, indigo carmine aluminium lake (E132) and carnauba wax.
• Printing ink: shellac gum, black iron oxide (E172), propylene glycol (E1520) and concentrated ammonia solution.

See end of section 2 – Kalydeco contains lactose and sodium.
Description of the appearance of Kalydeco and pack sizes
Kalydeco 75 mg film-coated tablets are blue, capsule-shaped tablets,
12.7 mm × 6.8 mm, with “V 75” printed in black ink on one side and smooth on the other.
The following pack sizes are available:

• Blister pack with cardboard support containing 28 film-coated tablets

Kalydeco 150 mg film-coated tablets are blue, capsule-shaped tablets,
16.5 mm × 8.4 mm, with “V 150” printed in black ink on one side and smooth on the other.
The following pack sizes are available:

• Blister pack with cardboard support containing 28 film-coated tablets
• Blister pack containing 56 film-coated tablets
• Bottle containing 56 film-coated tablets

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
Northern Ireland
BT63 5UA
United Kingdom
Millmount Healthcare Limited
Block-7, City North Business Campus
Stamullen
Co. Meath
K32 YD60
Ireland
For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien, България, Česká España
republika, Danmark, Deutschland, Eesti, Vertex Pharmaceuticals Spain, S.L.
France, Hrvatska, Ireland, Ísland, Κύπρος, Tel: + 34 91 7892800
Latvija, Lietuva, Luxembourg/Luxemburg,
Magyarország, Malta, Nederland, Norge,
Österreich, Polska, Portugal, România,
Slovenija, Slovenská republika,
Suomi/Finland, Sverige
Vertex Pharmaceuticals (Ireland) Limited
Tél/Tel/Teл/Tlf/Sími/Τηλ/Puh:
+353 (0) 1 761 7299
Ελλάδα Italia
Vertex Φαρμακευτική Μονοπρόσωπη Ανώνυμη Vertex Pharmaceuticals
Εταιρία (Italy) S.r.l.
Τηλ: +30 (211) 2120535 Tel: +39 0697794000
Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency, https://www.ema.europa.eu/. In addition, links to other websites on rare diseases and related therapeutic treatments are provided.

Package leaflet: information for the patient

Kalydeco 13.4 mg granules in sachet, 25 mg granules in sachet, 50 mg granules in sachet, 59.5 mg granules in sachet, 75 mg granules in sachet

ivacaftor
Please read this leaflet carefully before administering this medicine to the child, as it contains important information for the child.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult the child's doctor or pharmacist.
• This medicine has been prescribed for the child only. Do not give it to others, even if their symptoms are the same as the child's, because it could be harmful.
• If any adverse reaction occurs, including those not listed in this leaflet, contact the child's doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Kalydeco is and what it is used for
2. What you need to know before the 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 defective CFTR proteins to open more frequently, thereby improving the movement of chloride in and out of the cell.

Kalydeco granules are indicated:

• As monotherapy for the treatment of children aged 1 month and older and weighing between 3 kg and less than 25 kg with cystic fibrosis (CF) who have the CFTR mutation R117H or one of the following gating mutations in the CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R.
• In combination with ivacaftor/tezacaftor/elexacaftor granules for patients aged 2 to 6 years with CF who have at least one CFTR mutation responsive to Kalydeco in combination with ivacaftor/tezacaftor/elexacaftor. If you have been prescribed Kalydeco to be taken with ivacaftor/tezacaftor/elexacaftor, please read the package leaflet for that medicine, as it contains important information on how to take these two medicines.

2. What you should 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 takes Kalydeco.

• Talk to your child’s doctor if your child has or has previously had liver problems, as the dose may need to be adjusted.
• Increases in liver enzymes in the blood have been observed in some people treated with Kalydeco (alone or in combination with ivacaftor/tezacaftor/elexacaftor). Inform your child’s doctor immediately if your child experiences any of the following symptoms, which may be signs of liver problems:
  • Pain or discomfort in the upper right part of the abdomen
  • Yellowing of the skin or the whites of the eyes
  • Loss of appetite
  • Nausea or vomiting
  • Dark urine
• Your child’s doctor will order blood tests to monitor your child’s liver function before starting treatment and during treatment, especially during the first year, and particularly if previous blood tests have shown elevated liver enzyme levels.
• Depression (including suicidal thoughts and behaviours) has been reported in patients taking Kalydeco, mainly in combination therapy with ivacaftor/tezacaftor/elexacaftor, usually 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 harming yourself or of suicide, as these may be signs of depression.
• Inform your child’s doctor if your child has or has previously had kidney problems.
• If your child has two Class I mutations (mutations known not to produce the CFTR protein), Kalydeco should not be taken, as a response to this medicine is not expected.
• Kalydeco is not recommended for patients who have undergone organ transplantation.
• A lens abnormality (cataract), without effect on vision, has been observed in some children and adolescents during treatment (alone or in combination with ivacaftor/tezacaftor/elexacaftor). Your child’s doctor may perform eye examinations before and during treatment.
• Kalydeco should only be used in the presence of one of the CFTR gene mutations listed in section 1 (What Kalydeco is and what it is used for).

Children
Do not give this medicine to children under 1 month of age, as it is not known whether ivacaftor is safe and effective in these children.
Do not give this medicine in combination with ivacaftor/tezacaftor/elexacaftor to children under 2 years of age, as it is not known whether it is safe and effective in this age group.

Other medicines and Kalydeco
Tell your child’s doctor or pharmacist if your child is taking, has recently taken, or might 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 perform additional monitoring.

• Antifungal medicines (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.
• Antiepileptic medicines (used to treat seizures or epileptic attacks). These include carbamazepine, phenobarbital and phenytoin.
• Herbal medicines. These include St. John’s wort (Hypericum perforatum).
• Immunosuppressants (used after organ transplantation). These include ciclosporin, everolimus, sirolimus and tacrolimus.
• Cardiac glycosides (used to treat certain heart conditions). These include digoxin.
• Anticoagulant medicines (used to prevent blood clots). These include warfarin.
• Diabetes medicines. These include glimepiride and glipizide.
• Medicines to lower blood pressure. These include verapamil.

Kalydeco with food and drinks
Avoid giving your child food or drinks containing grapefruit during treatment, as these can 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. If your child experiences dizziness, your child should not ride a bicycle or do anything else that requires full attention.

Kalydeco contains lactose and sodium
If your child’s doctor has diagnosed an intolerance to certain sugars, contact the doctor before your child takes this medicine.
Kalydeco contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially ‘sodium-free’.

3. How to take Kalydeco

Give this medicine to the child exactly as instructed by the child's doctor. If you
have any doubts, consult the child's doctor.
The child's doctor will determine the correct dose to administer. The child must continue taking all
other medicines they usually use, unless the child's doctor advises stopping
them.
Dosing recommendations for Kalydeco are shown in Table 1.
Table 1: Dosing recommendations

Administer the morning and evening granules to the child approximately 12 hours apart.
If the child has liver problems, the child's doctor may need to reduce the dose of
Kalydeco, as the liver will not eliminate the medicine as quickly as in
children with normal liver function.

• Moderate liver problems in children aged 6 months and older: the dose may be reduced to half of the dose indicated in the previous table, i.e. one sachet once daily.
• Severe liver problems in children aged 6 months and older: use is not recommended; however, the child's doctor will decide whether the child should take this medicine. If so, the dose (as indicated in the previous table) should be reduced to one sachet every other day.
• Liver problems in children aged between 1 month and 6 months: use is not recommended.

Kalydeco is for oral use.
Each sachet is for single use only.
How to give Kalydeco to the child:

• Take the granule sachet, holding it with the dotted line at the top.
• Gently shake the sachet to settle the contents at the bottom.
• Tear or cut the sachet along the dotted line.
• Mix the entire contents of the sachet with 5 mL of soft or liquid age-appropriate food. The food or liquid should be at room temperature or cooler. Examples of suitable foods or liquids include fruit or vegetable puree, yogurt, apple sauce, water, milk, breast milk, infant formula, or juice.
• After mixing, give the mixture to the child immediately. If this is not possible, give it within one hour of mixing. Ensure that the mixture is consumed immediately and completely.
• Immediately before or immediately after administration, give the child a meal or snack containing fat (some examples are provided below).

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

• cheese, whole milk, whole milk dairy products, yogurt, breast milk, infant formula, chocolate
• meat, oily fish
• avocado, hummus, soy-based products (tofu)
• nuts, protein bars or protein-containing beverages with fat

If the child takes more Kalydeco than they should
Adverse effects may occur, including those listed in section 4 below. In this case, contact the child's doctor or pharmacist for advice. If possible, keep the medicine and this leaflet with you.
If you forget to give Kalydeco to the child
Give the missed dose if less than 6 hours have passed since the scheduled time. Otherwise, wait until the next regularly scheduled dose. Do not give a double dose to make up for a forgotten dose.
If you stop the child's treatment with Kalydeco
Give Kalydeco to the child for the entire duration recommended by the child's doctor. Do not stop treatment unless instructed by the doctor. If you have any doubts about using this medicine, consult the child's doctor or pharmacist.

4. Possible side effects

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

Serious side effects

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

Possible signs of liver problems

An increase in liver enzymes in the blood is common in patients with CF and has also been reported in patients taking Kalydeco alone or in combination with ivacaftor/tezacaftor/elexacaftor.

Liver damage and worsening of liver function have been reported in patients treated with Kalydeco in combination with ivacaftor/tezacaftor/elexacaftor, particularly in individuals with severe liver disease. Worsening liver function can be serious and may require liver transplantation.

The following symptoms may be signs of liver problems:

• pain or discomfort in the upper right part of the stomach (abdomen)
• yellowing of the skin or whites of the eyes
• loss of appetite
• nausea or vomiting
• dark urine

Depression

Signs include depressed or changed mood, anxiety, and feelings of emotional distress.

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

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

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

Common side effects (may affect up to 1 in 10 people)

• Runny nose
• Earache, ear disorder
• Ringing in the ears (tinnitus)
• Redness inside the ear
• Inner ear disorder (feeling of vertigo or spinning head)
• Sinus problems (sinus congestion)
• Redness in the throat
• Breast mass
• Nausea
• Influenza
• Low blood sugar levels (hypoglycaemia)
• Abnormal breathing (shortness of breath or difficulty breathing)
• Intestinal gas (flatulence)
• Acne
• Itching of the skin
• Increased creatine phosphokinase (a sign of muscle breakdown) observed in blood tests

Uncommon side effects (may affect up to 1 in 100 people)

• Ear congestion
• Inflammation of the breast
• Breast enlargement in males
• Changes or pain in the nipple
• Wheezing
• Increased blood pressure

Not known (frequency cannot be estimated from the available data)

• Liver damage (liver injury)
• Increased bilirubin levels (a blood test for liver function)

Additional side effects in children and adolescents

Side effects observed in children and adolescents are similar to those seen in adults. However, increases in liver enzymes in the blood are observed more frequently in younger children.

Reporting of side effects

If the child experiences any side effect, including those not listed in this leaflet, talk to the child’s doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Kalydeco

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the cardboard package, on the carrier
and on the sachet after "Exp./EXP". The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Once mixed, the mixture has been shown to be stable for one hour.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Kalydeco contains
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: anhydrous colloidal silica, sodium croscarmellose, hypromellose acetate succinate,
lactose monohydrate, magnesium stearate, mannitol, sucralose and sodium lauryl sulfate (E487).
See the end of section 2 for information on lactose and sodium content in Kalydeco.

Description of the appearance of Kalydeco and contents of the pack
Kalydeco 13.4 mg granules in sachet are white to off-white in colour.
Kalydeco 25 mg granules in sachet are white to off-white in colour.
Kalydeco 50 mg granules in sachet are white to off-white in colour.
Kalydeco 59.5 mg granules in sachet are white to off-white in colour.
Kalydeco 75 mg granules in sachet are white to off-white in colour.
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 of 56 sachets (contains 4 individual cartons of 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 of 28 sachets (contains 4 individual cartons of 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
Northern Ireland
BT63 5UA
United Kingdom

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

België/Belgique/Belgien, България, Česká republika, Danmark, Deutschland, Eesti, España, France, Hrvatska, Ireland, Ísland, Κύπρος, Latvija, Lietuva, Luxembourg/Luxemburg, Magyarország, Malta, Nederland, Norge, Österreich, Polska, Portugal, România, Slovenija, Slovenská republika, Suomi/Finland, Sverige
Vertex Pharmaceuticals (Ireland) Limited
Tél/Tel/Teл/Tlf/Sími/Τηλ/Puh: +353 (0)1 761 7299

Ελλάδα
Vertex Φαρμακευτική Μονοπρόσωπη Ανώνυμη Εταιρία
Τηλ: +30 (211) 2120535

Italia
Vertex Pharmaceuticals (Italy) S.r.l.
Tel: +39 0697794000

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu/. In addition, links to other websites on rare diseases and related therapeutic treatments are provided.