Kalydeco 75 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Kalydeco 75 mg film-coated tablets

Kalydeco 150 mg film-coated tablets

Ivacaftor

Read the 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 have any questions, ask your doctor or pharmacist.
• 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 effects, consult your doctor or pharmacist, even if these 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 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 allowing particles such as chloride to move in and out of 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 flow of chloride into and out of the cell.

Kalydeco tablets are indicated:

• As monotherapy for patients aged 6 years and older with a body weight of 25 kg or more who have cystic fibrosis (CF) and a 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 tezacaftor/ivacaftor tablets for 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 a specific second mutation leading to 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 to be taken with tezacaftor/ivacaftor, please read the tezacaftor/ivacaftor package leaflet. It contains important information on how to take these two medicines.

• In combination with ivacaftor/tezacaftor/elexacaftor tablets for patients aged 6 years and older who have CF and at least one CFTR gene mutation that responds 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 ivacaftor/tezacaftor/elexacaftor. 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 starting Kalydeco.

• Talk to your doctor if you have or have previously had liver problems. Your doctor may need to adjust your dose.

• Increased liver enzymes in the blood have been observed in some people taking Kalydeco (alone or in combination with tezacaftor/ivacaftor or ivacaftor/tezacaftor/elexacaftor). Contact your doctor immediately if you experience any of the following symptoms, which may indicate 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

• Your doctor will perform blood tests to monitor your liver function before and during treatment, especially during the first year, and particularly if previous blood tests showed elevated liver enzymes.

• Depression (including suicidal thoughts and suicidal behaviour) has been reported in patients taking Kalydeco, mainly in combination regimens with tezacaftor/ivacaftor or 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 altered mood, anxiety, feelings of emotional distress, or thoughts of self-harm or suicide, which may be signs of depression.

• Talk to 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 if you have received an organ transplant.

• Talk to your doctor if you are using hormonal contraceptives, for example, women taking oral contraceptive pills. This may increase the likelihood of developing a skin rash while taking Kalydeco in combination with ivacaftor/tezacaftor/elexacaftor.

• In some children and adolescents treated with Kalydeco (alone or in combination with tezacaftor/ivacaftor or ivacaftor/tezacaftor/elexacaftor), an eye lens abnormality (cataract) has been observed, without any effect on vision.

• 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

This medicine should not be given to children under 1 month of age, as the safety and efficacy of ivacaftor in these children are unknown.

This medicine should not be given 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 the safety and efficacy of ivacaftor in these children are unknown.

Other medicines and Kalydeco

Tell your doctor or pharmacist if you are taking, have 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 doctor if you are taking any of the following medicines. Your doctor may decide to adjust your dose or schedule additional 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

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

Pregnancy and breastfeeding

If you are pregnant, breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor before using this medicine. If possible, it may be preferable to avoid using Kalydeco during pregnancy, 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 stopping treatment with ivacaftor, 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 feel dizzy, do not drive, ride a bicycle, or operate machinery.

Kalydeco contains lactose and sodium

If your doctor has informed you that you have an intolerance to certain sugars, consult with him before taking this medicine.

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

3. How to take Kalydeco

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

Your doctor will determine which medication and dose are appropriate 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 food containing fat.

You must continue taking all other medications you are using, unless your doctor tells you to stop taking any of them.

If you have moderate or severe liver problems, your doctor may need to reduce your dose, as your liver will not eliminate the medication as quickly as in people with normal liver function.

This medicine is to be taken by mouth.

Swallow the tablet whole. Do not break, chew, or dissolve the tablets. Take Kalydeco tablets with food containing fat.

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

• Cheese, whole milk, whole dairy products, yogurt, chocolate
• Meats, fatty fish
• Avocado, hummus (chickpea purée), soy-based products (tofu)
• Nuts, nutritional bars, or nutritional drinks containing fat

If you take more Kalydeco than you should

You may experience adverse effects, including those listed in section 4 below. If this happens, consult your doctor or pharmacist. If possible, show them the medicine and this leaflet.

If you forget to take Kalydeco

Take the missed dose if less than 6 hours have passed since the time you were supposed to take it. Otherwise, wait until it is time for your next dose to be taken as usual. Do not take a double dose to make up for missed doses.

If you stop taking Kalydeco

Take Kalydeco for as long as your doctor has recommended. Do not stop treatment unless your doctor tells you to.

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 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 tezacaftor/ivacaftor or ivacaftor/tezacaftor/elexacaftor.

Liver damage and worsening of liver function have been reported in patients taking Kalydeco in combination with ivacaftor/tezacaftor/elexacaftor, particularly in individuals with severe liver disease. Worsening of liver function may be serious and could 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 whites 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 doctor immediately if you experience any of these symptoms.

Very common adverse effects (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 types of bacteria in mucus
• Increased liver enzymes (signs of liver stress)
• Rash

Common adverse effects (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 spinning)
• Sinus problems (sinus congestion)
• Redness in the throat
• Breast lump
• Feeling of nausea
• Influenza (flu)
• Low blood sugar level (hypoglycaemia)
• Abnormal breathing (shortness of breath or difficulty breathing)
• Flatulence (wind)
• Acne
• Itchy skin
• Increased creatine phosphokinase (a sign of muscle breakdown), observed in blood tests

Uncommon adverse effects (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
• Increases in 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 seen in adults. However, increased liver enzymes in the blood are more frequent in younger children.

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 can 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 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 label of the bottle following EXP. The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to properly dispose of unused medicines and their packaging. This will help protect the environment.

6. Pack contents and other information

Composition of Kalydeco

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, lactose monohydrate, 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, black iron oxide (E172), propylene glycol (E1520), and concentrated ammonia solution.

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

Nature of the product and pack sizes

Kalydeco 75 mg film-coated tablets are capsule-shaped, light blue in colour, measure 12.7 mm × 6.8 mm, and are printed with “V 75” in black ink on one side and blank on the other.

The following pack sizes are available:

• Box with blister packs containing 28 film-coated tablets

Kalydeco 150 mg film-coated tablets are capsule-shaped, light blue in colour, measure 16.5 mm × 8.4 mm, and are printed with “V 150” in black ink on one side and blank on the other.

The following pack sizes are available:

• Box with blister packs containing 28 film-coated tablets
• Box of blisters 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
County Armagh
BT63 5UA
United Kingdom (Northern Ireland)

Millmount Healthcare Limited
Block-7, City North Business Campus
Stamullen
Co. Meath
K32 YD60
Ireland

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 medicine is available on the website of the European Medicines Agency: https://www.ema.europa.eu. There are also links to other websites on rare diseases and orphan medicinal products.