Document Details

Generated Narrative: Bundle TEST PURPOSES ONLY - kalydeco

Document Subject

Generated Narrative: MedicinalProductDefinition mpf7594bb39e512c1a930c8153ce8d7d94

identifier: http://ema.europa.eu/identifier/EU/1/12/782/001

type: Medicinal Product

domain: Human use

status: active

legalStatusOfSupply: Medicinal product subject to medical prescription

name

productName: Kalydeco 75 mg film-coated tablets

type: Full name

part

part: nan

type: Invented name part

part

part: nan

type: Scientific name part

part

part: nan

type: Strength part

part

part: nan

type: Pharmaceutical dose form part

Usages

-	Country	Jurisdiction	Language
*	EU	EU	en

Document Content

Generated Narrative: Composition composition-en-f7594bb39e512c1a930c8153ce8d7d94

identifier: http://ema.europa.eu/identifier/EU/1/12/782/001

status: Final

type: Package Leaflet

category: Raw

date: 2022-02-16 13:28:17+0000

author: Organization ACME industry

title: TEST PURPOSES ONLY - kalydeco

Attesters

What is in this leaflet

1. What Kalydeco is and what it is used for
2. What you need to know before you take Kalydeco
3. How to take Kalydeco
4. Possible side effects
5. How to store Kalydeco
6. Contents of the pack and other information

Kalydeco contains the active substance ivacaftor. Ivacaftor acts at the level of the cystic fibrosis transmembrane conductance regulator (CFTR), a protein that forms a channel at the cell surface that allows the movement of particles such as chloride in and out of the cell. Due to mutations in the CFTR gene (see below), chloride movement is reduced in those with cystic fibrosis (CF). Ivacaftor helps certain abnormal CFTR proteins open more often to improve chloride movement in and out of the cell.

Kalydeco tablets are indicated:

• As monotherapy for patients aged 6 years and older and weighing 25 kg or more with cystic fibrosis (CF) who have an 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 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 an F508del mutation and certain other second mutations that result in reduced amount 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, read the package leaflet of the latter. It contains important information about how to take these two medicines.

• In combination with ivacaftor/tezacaftor/elexacaftor tablets for patients aged 6 years and over who have CF, with at least one F508del mutation in the CFTR gene. If you have been prescribed Kalydeco to be taken with ivacaftor/tezacaftor/elexacaftor, read the package leaflet of the latter. It contains important information about how to take these two medicines.

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 taking Kalydeco.

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

• Increased liver enzymes in the blood have been seen in some people receiving Kalydeco (alone or in combination with tezacaftor/ivacaftor or ivacaftor/tezacaftor/elexacaftor). Tell your doctor right away if you have any of these symptoms, which may be a sign of liver problems: Pain or discomfort in the upper right stomach (abdominal) area Yellowing of the skin or the white part of the eyes Loss of appetite Nausea or vomiting Dark urine

• Your doctor will do some blood tests to check your liver before and during treatment, particularly during the first year and especially if your blood tests showed high liver enzymes in the past.

• Talk to your doctor if you have kidney problems or have previously had them.

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

• Talk to your doctor if you are using hormonal contraception for example, women using the contraceptive pill. This may mean you are more likely to get a rash while taking Kalydeco in combination with ivacaftor/tezacaftor/elexacaftor.

• Abnormality of the eye lens (cataract) without any effect on vision has been noted in some children and adolescents treated with Kalydeco (alone or in combination with tezacaftor/ivacaftor or ivacaftor/tezacaftor/elexacaftor). Your doctor may perform some eye examinations prior to and during treatment.

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

Children and adolescents

Do not give this medicine to children under 4 months of age as it is not known if ivacaftor is safe and effective in these children.

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 it is not known if they are safe and effective for them.

Other medicines and Kalydeco

Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines. Some medicines can affect how Kalydeco works or make side effects more likely. In particular, tell your doctor if you are taking any of the medicines listed below. Your doctor may decide to adjust your dose or that you need extra check-ups.

• Antifungal medicines (used for the treatment of fungal infections). These include fluconazole, itraconazole, ketoconazole, posaconazole, and voriconazole.
• Antibiotic medicines (used for the treatment of bacterial infections). These include clarithromycin, erythromycin, rifabutin, rifampicin, and telithromycin.
• Epilepsy medicines (used for the treatment of epileptic seizures or fits). These include carbamazepine, phenobarbital, and phenytoin.
• Herbal medicines. These include St. John s wort (Hypericum perforatum).
• Immunosuppressants (used after an organ transplantation). These include ciclosporin, everolimus, sirolimus, and tacrolimus.
• Cardiac glycosides (used for the treatment of some heart conditions). These include digoxin.
• Anticoagulant medicines (used to prevent blood clots). These include warfarin.
• Medicines for diabetes. These include glimepiride and glipizide.
• Medicines for lowering blood pressure. These include verapamil.

Kalydeco with food and drink

Avoid food or drink containing grapefruit during treatment as these may increase the side effects of Kalydeco by increasing the amount of ivacaftor in your body.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. It may be better to avoid using Kalydeco during pregnancy, if possible, and your doctor will help you decide what is best for you and your child.

It is unknown whether ivacaftor is excreted in human milk. If you plan to breast-feed, ask your doctor for advice before taking Kalydeco. Your doctor will decide whether to recommend that you stop breast-feeding or for you to stop ivacaftor therapy. Your doctor will take into account the benefit of breast-feeding for the child and the benefit of therapy for you.

Driving and using machines

Kalydeco can make you dizzy. If you feel dizzy, do not drive, cycle or use machines.

Kalydeco contains lactose and sodium.

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

Kalydeco contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially sodium-free .

Always take this medicine exactly as your doctor has told you to. Check with your doctor if you are not sure.

Your doctor will determine which medicine and dose is right for you.

Kalydeco dosing recommendations are provided in Table 1. Table 1: Dosing recommendations

Morning Evening Kalydeco as monotherapy 6 years and older, 25 kg One Kalydeco 150 mg tablet One Kalydeco 150 mg tablet Kalydeco in combination with tezacaftor/ivacaftor 6 years to less than 12 years, < 30 kg One tezacaftor 50 mg/ivacaftor 75 mg tablet One Kalydeco 75 mg tablet 6 years to less than 12 years, 30 kg One tezacaftor 100 mg/ivacaftor 150 mg tablet One Kalydeco 150 mg tablet 12 years and older One tezacaftor 100 mg/ivacaftor 150 mg tablet One Kalydeco 150 mg tablet Kalydeco in combination with ivacaftor/tezacaftor/elexacaftor 6 years to less than 12 years, < 30 kg Two ivacaftor 37.5 mg/tezacaftor 25 mg/elexacaftor 50 mg tablets One Kalydeco 75 mg tablet 6 years to less than 12 years, 30 kg Two ivacaftor 75 mg/tezacaftor 50 mg/elexacaftor 100 mg tablets One Kalydeco 150 mg tablet 12 years and older Two ivacaftor 75 mg/tezacaftor 50 mg/elexacaftor 100 mg tablets One Kalydeco 150 mg tablet

Take the morning and evening doses approximately 12 hours apart with food that contains fat.

You must keep using all other medicines you use, unless your doctor tells you to stop using any.

If you have liver problems, either moderate or severe, your doctor may need to reduce the dose of your tablets, because your liver will not clear the medicine as fast as in people who have normal liver function.

This medicine is for oral use.

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

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

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

If you take more Kalydeco than you should

You may experience side effects, including those mentioned in section 4 below. If so, contact your doctor or pharmacist to ask for advice. If possible, have your medicine and this leaflet with you.

If you forget to take Kalydeco

Take the missed dose if less than 6 hours have passed since the time you missed the dose. Otherwise, wait until your next scheduled dose as you normally would. 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 unless your doctor advises you to.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

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

Serious side effects

Stomach (abdominal) ache 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.

In patients taking Kalydeco in combination with ivacaftor/tezacaftor/elexacaftor, liver damage and worsening of liver function in people with severe liver disease has been reported. The worsening of liver function can be serious and may require transplantation.

These may be signs of liver problems:

• Pain or discomfort in the upper right area of the stomach (abdominal) area
• Yellowing of the skin or white part of the eyes
• Loss of appetite
• Nausea or vomiting
• Dark urine

Tell your doctor straight away if you have any of these symptoms.

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

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

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

• Runny nose
• Ear pain, ear discomfort
• Ringing in the ears
• Redness inside the ear
• Inner ear disorder (feeling dizzy or spinning)
• Sinus problems (sinus congestion)
• Redness in the throat
• Breast mass
• Feeling sick (nausea)
• Flu
• Low blood sugar (hypoglycaemia)
• Abnormal breathing (shortness of breath or difficulty breathing)
• Wind (flatulence)
• Spots (acne)
• Itchy skin
• Increased creatine phosphokinase (sign of muscle breakdown) seen in blood tests

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

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

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

• Damage to the liver (liver injury)
• Raised bilirubin measurement (liver blood test)

Additional side effects in children and adolescents

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

Reporting of side effects

If you get 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.

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 bottle label after EXP. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

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 ingredients are:

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

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

What Kalydeco looks like and contents of the pack

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

The following pack sizes are available:

• Blister card pack containing 28 film-coated tablets

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

The following pack sizes are available:

• Blister card pack 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 F2, Northwood Court, Santry,
Dublin 9, D09 T665,
Ireland Tel: +353 (0)1 761 7Manufacturer

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 YDIreland

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

Belgi /Belgique/Belgien, , esk republika, Danmark, Deutschland, Eesti, France, Hrvatska, Ireland, sland, , Latvija, Lietuva, Luxembourg/Luxemburg, Magyarorsz g, Malta, Nederland, Norge, sterreich, Polska, Portugal, Rom nia, Slovenija, Slovensk republika, Suomi/Finland, Sverige, United Kingdom (Northern Ireland) Vertex Pharmaceuticals (Ireland) Limited T l/Tel/Te /Tlf/S mi/ /Puh:
+353 (0) 1 761 7Espa a Vertex Pharmaceuticals Spain, S.L. Tel: + 34 91 7892
Vertex
: +30 (211) 2120Italia Vertex Pharmaceuticals (Italy) S.r.l. Tel: +39 0697794This leaflet was last revised in

Other sources of information Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments. Package leaflet: Information for the patient

Kalydeco 25 mg granules in sachet Kalydeco 50 mg granules in sachet Kalydeco 59.5 mg granules in sachet Kalydeco 75 mg granules in sachet ivacaftor

Read all of this leaflet carefully before your child starts taking this medicine because it contains important information for your child.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your child s doctor or pharmacist.
• This medicine has been prescribed for your child only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as your child s.
• If your child gets any side effects, talk to your child s doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.