KALYDECO 75 mg FILM-COATED TABLETS

2. What you need to know before you take Kalydeco

Do not take Kalydeco

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

Warnings and precautions

Talk to your doctor or pharmacist before you start taking Kalydeco.

• Tell your doctor if you have or have had liver problems. Your doctor may need to adjust your dose.
• An increase in liver enzymes in the blood has been seen in some people taking Kalydeco (alone or in combination with tezacaftor/ivacaftor or ivacaftor/tezacaftor/elexacaftor). Tell your doctor right away if you have any of the following symptoms, which may be signs of liver problems:
• Pain or discomfort in the upper right stomach area
• Yellowing of the skin or the white part of the eyes
• Lack of appetite
• Feeling sick (nausea) or vomiting
• Dark urine

• Your doctor will do blood tests to check how your liver is working before and during treatment, especially during the first year and especially if your blood tests have shown that you have had elevated liver enzymes in the past.

• Depression (including thoughts of suicide or suicidal behavior) has been reported in patients taking Kalydeco, mainly in combination with tezacaftor/ivacaftor or ivacaftor/tezacaftor/elexacaftor, usually appearing in the first three months of treatment. Tell your doctor right away if you (or someone taking this medicine) experience any of the following symptoms: feeling sad or changed mood, anxiety, feeling emotionally unwell, or thoughts of self-harm or suicide, which may be signs of depression.

• Tell your doctor if you have or have had kidney problems.

• If you have two Class I mutations (mutations known not to produce the CFTR protein), you should not take Kalydeco, as it is not expected to respond to this medicine.

• Kalydeco is not recommended if you have had an organ transplant.

• Tell your doctor if you are using hormonal contraceptives, for example, women using the contraceptive pill. It may mean that you are more likely to get a 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), a cataract (an abnormality in the lens of the eye) has been seen without any effect on vision.

• Your doctor may do some eye examinations before and during treatment.

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

Children and adolescents

This medicine must not be given to children under 1 month of age, as it is not known if ivacaftor is safe and effective in these children.

This medicine must 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 it is not known if ivacaftor is safe and effective in them.

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 how Kalydeco works or make it more likely that you will have side effects. In particular, tell your doctor if you are taking any of the following medicines. Your doctor may decide to adjust your dose or that you need 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, rifampicin, and telithromycin.
• Medicines for epilepsy(used to treat seizures or fits). These include carbamazepine, phenobarbital, and phenytoin.
• Herbal medicines.These include St. John's Wort (Hypericum perforatum).
• Immunosuppressants(used after an organ transplant). These include ciclosporin, 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 food or drink containing grapefruit during treatment, as it may increase the risk of side effects of Kalydeco by increasing the amount of ivacaftor in the body.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine. If possible, it may be preferable to avoid the use of Kalydeco during pregnancy, and your doctor will help you make a decision that is best for you and your baby.

Ivacaftor is excreted in breast milk. If you are breastfeeding, ask your doctor for advice before taking Kalydeco. Your doctor will decide whether to recommend that you stop breastfeeding or stop treatment with ivacaftor. Your doctor will consider the benefit of breastfeeding for your child and the benefit of treatment for you.

Driving and using machines

Kalydeco may cause dizziness. If you feel dizzy, do not drive, ride a bicycle, or use machines.

Kalydeco contains lactose and sodium

If your doctor has told you that you have an intolerance to some sugars, contact them 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

Always take this medicine exactly as your doctor has told you. If you are not sure, check with your doctor.

Your doctor will decide which medicine and dose is suitable for you.

Dosing recommendations for Kalydeco are provided in Table 1.

Table 1: Dosing recommendations

Take the morning and evening doses approximately 12 hours apart with fat-containing foods.

You should continue to use all your other medicines as you have been told by your doctor, unless your doctor tells you to stop taking any of them.

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

This medicine is for oral use.

Swallow the tablet whole. Do not break, crush, or chew the tablets. Take Kalydeco tablets with fat-containing foods.

Fat-containing foods and snacks include those prepared with butter or oils or those that contain eggs. Other fat-containing foods are:

• Cheese, whole milk, whole-milk dairy products, yogurt, chocolate
• Meat, oily fish
• Avocado, hummus (chickpea paste), soy products (tofu)
• Nuts, nut bars, or nutritional drinks that contain fat

If you take more Kalydeco than you should

You may experience side effects, including those mentioned in section 4 below. If this happens, talk to your doctor or pharmacist. If possible, show them the medicine and this leaflet.

If you forget to take Kalydeco

Take the missed dose if it is less than 6 hours since the time you should have taken the dose. Otherwise, wait until it is time for your next dose. Do not take a double dose to make up for a forgotten dose.

If you stop taking Kalydeco

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

If you have any further questions on the use of this medicine, ask 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 pain (abdominal) and increased liver enzymes in the blood.

Signs of liver problems

Increased liver enzymes in the blood are common in patients with cystic fibrosis 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/elexacaftorin 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 stomach area.
• Yellowing of the skin or the white part of the eyes.
• Lack of appetite.
• Feeling sick (nausea) or vomiting.
• Dark urine.

Depression

Signs of depression include feeling sad or changed mood, anxiety, or feeling emotionally unwell.

Tell your doctor right awayif 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
• Diarrhea
• Stomach pain or abdominal pain
• Changes in the type of bacteria in the mucus
• Increased liver enzymes (signs of liver stress)
• Rash

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

• Nasal congestion
• Ear pain, discomfort in the ear
• Ringing in the ears
• Redness inside the ear
• Inner ear disorder (feeling dizzy or that everything is spinning)
• Sinus problems (sinus congestion)
• Redness in the throat
• Lump in the breast
• Feeling sick (nausea)
• Flu
• Low blood sugar (hypoglycemia)
• Abnormal breathing (shortness of breath or difficulty breathing)
• Wind (flatulence)
• Spots (acne)
• Itching of the skin
• Increased creatine phosphokinase (sign of muscle breakdown), seen in blood tests

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

• Ear blockage
• Breast inflammation
• Breast enlargement in men
• Changes or pain in the nipples
• Wheezing
• Increased blood pressure

Frequency not known(cannot be estimated from the available data)

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

Additional side effects in children and adolescents

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

Reporting of side effects

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

5. Storing Kalydeco

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

Do not use this medicine after the expiry date which is stated on the carton, blister, and label after EXP. The expiry date is the last day of the month stated.

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 dispose of medicines no longer required. These measures will help protect the environment.

6. Package Contents and Additional Information

Kalydeco Composition

The active ingredient 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 ingredients are:

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

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

Product Appearance and Packaging Contents

Kalydeco 75 mg film-coated tablets are capsule-shaped, light blue in color, measure 12.7 mm × 6.8 mm, and are printed with "V 75" in black ink on one side and nothing 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 color, measure 16.5 mm × 8.4 mm, and are printed with "V 150" in black ink on one side and nothing on the other.

The following pack sizes are available:

• Box with blister packs containing 28 film-coated tablets
• Blister pack containing 56 film-coated tablets
• Bottle containing 56 film-coated tablets

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

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 authorization holder:

Date of Last Revision of this Leaflet:

Other Sources of Information

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