InfoCons Consumer Protection informs you – Kaftrio – Package Leaflet

Before anything else

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

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

ℹ️ 1. What Kaftrio is and what it is used for

Kaftrio contains three active substances: ivacaftor , tezacaftor and elexacaftor . The medicine helps lung cells to work better in some patients with cystic fibrosis (CF). CF is an inherited condition in which the lungs and the digestive system can become clogged with thick, sticky mucus .

Kaftrio taken with ivacaftor is for patients aged 2 to less than 6 years who have CF , with at least one mutation in the CFTR (cystic fibrosis transmembrane conductance regulator) gene that is responsive to Kaftrio . It is intended as a long-term treatment .

Kaftrio works on a protein called CFTR . The protein i s damaged in some people with CF , if they have a mutation in the CFTR gene.

Kaftrio is normally taken with another medicine, ivacaftor. Ivacaftor causes the protein to work better , while tezacaftor and elexacaftor increase the amount of protein at the cell surface.

Kaftrio (taken with ivacaftor ) helps your child’s breathing by improving his/her lung function. You may also notice that your child does not get ill as often , or that it is easier for your child to gain weight.

⚠️ 2. What you need to know before you r child takes Kaftrio

Do not give your child Kaftrio :

• If you r child is allergic to ivacaftor, tezacaftor, elexacaftor, or any other ingredients of this medicine (listed in section 6).
• Talk to your child’s doctor and do not give your child this medicine, if this applie s to your child .

Warnings and precautions

Talk to your child’s doctor if you r child has liver problems or have had them previously. Your doctor may need to adjust your child’s dose (see section 4) .

• Your doctor will do some blood tests to check your child’s liver before and during treatment with Kaftrio, especially if your child’s blood tests showed high liver enzymes in the past. Liver enzymes in the blood can increase in patients receiving Kaftrio.

Tell your doctor right away if your child has any symptoms of liver problems. These are listed in section 4.

• Depression (including suicidal thoughts , changes in behaviour s, anxiety , and sleep disorders) has been reported in patients while taking Kaftrio, usually starting within the first three months of treatment. Talk to your doctor straight away if you (or someone taking this medicine) experience any of the following symptoms which may be signs of depression: sad or altered mood, anxiety, feelings of emotional discomfort or thoughts of harming or killing yourself , and/or sleep difficulties (see section 4).

Talk to your doctor if you recognize behaviour al changes in your child within the first 2 months of treatment initiation.

• Talk to your child’s doctor if you r child has kidney problems, or your child has previously had them.
• If your child has two Class I mutations (mutations known not to make CFTR protein) you should not give Kaftrio to your child , as they are not expected to respond to this medicine.
• Talk to your child’s doctor before starting treatment with Kaftrio if your child has received an organ transplant .
• Your child’s doctor may do eye examinations before and during treatment with Kaftrio.

Cloudiness of the eye lens (cataract) without any effect on vision has occurred in some children and adolescents receiving this treatment.

Children under 2 years Do not give Kaftrio granules to children under the age of 2 years because it is not known if Kaftrio granules are safe and effective in this age group .

Other medicines and Kaftrio

Tell your child’s doctor or pharmacist if your child is taking, has recently taken, or might take any other medicines. Some medicines can affect how Kaftrio works or may make side effects more likely. In particular, tell your child’s doctor if you take any of the medicines listed below. Your child’s doctor may change the dose of one of the medicines if your child takes any of these.

• Antifungal medicines (used for the treatment of fungal infections). These include flucona zole, itraconazole, ketoconazole, posaconazole and voriconazole .
• Antibiotic medicines (used for the treatment of bacterial infections) . These include clarithromycin, erythromycin, rifampicin , rifabutin 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).

105 • 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 , glipizide , glyburide, nateglinide and repaglinide .
• Medicines for lowering blood cholesterol. These include pitavastatin and rosuvastatin.
• Medicines for lowering blood pressure. These include verapamil.

Kaftrio with food and drink Avoid giving your child food or drinks containing grapefruit during treatment as these may increase the side effects of Kaftrio by increasing the amount of Kaftrio in your child’s body.

Driving and using machines

Kaftrio can make your child dizzy. If you r child feels dizzy , it is advised that your child does not ride his/her bike or do anything else that needs his/her full attention.

Kaftrio granules contains lactose and sodium

If you have been told by your child’s doctor that your child has an intolerance to some sugars, contact your child’s doctor before your child takes this medicine.

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

💊 3. How to take Kaftrio

Always give your child this medicine exactly as your child’s doctor or pharmacist has told you. Check with your child’s doctor or pharmacist if you are not sure.

Your child’s doctor will determine the correct dose for your child . Your child must keep using all other medicines, unless your child’s doctor tells him/her to stop using any.

Kaftrio is usually taken with ivacaftor.

Recommended dose for patients aged 2 to less than 6 years Age Weight Morning dose Evening dose 2 to less than 6 years 10 kg to < 14 kg One sachet of ivacaftor 60 mg/tezacaftor 40 mg/elexacaftor 80 mg granules One sachet of ivacaftor 59.5 mg granules ≥ 14 kg One sachet of ivacaftor 75 mg/tezacaftor 50 mg/elexacaftor 100 mg granules One sachet of ivacaftor 75 mg granules Give your child the morning and evening doses about 12 hours apart.

The granules are for oral use.

To prepare Kaftrio granules:

• Hold the sachet with the cut line on top.
• Shake the sachet gently to settle the Kaftrio granules.
• Tear or cut sachet open along cut line.

106 • Carefully pour all the Kaftrio granules in the sachet into 1 teaspoon (5 mL) of soft food or liquid in a small container (like an empty bowl). Look inside the sachet to make sure there are no granules left inside. o The food or liquid should be at or below room temperature. o Examples of soft foods or liquids include pureed fruits, flavoured yogurt or pudding, and milk or juice.

• Mix the Kaftrio granules with food or liquid.

After mixing, give Kaftrio within 1 hour. Make sure all the medicine is taken.

Give both Kaftrio and ivacaftor doses 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 Avoid giving your child food and drink containing grapefruit while your child is taking Kaftrio. See Kaftrio with food and drink in section 2 for more details.

If you r child has liver pro blems, either moderate or severe, your child’s doctor may reduce the dose of your child’s medicine or decide to stop treatment with Kaftrio . See also Warnings and precautions in section 2.

If you r child takes more Kaftrio than he/she should Contact your child’s doctor or pharmacist for advice. If possible, take your child’s medicine and this leaflet with you. You r child may get side effects, including those mentioned in section 4 below.

If you forget to give your child Kaftrio If you forget to give your child a dose, work out how long it is since the missed dose.

• If less than 6 hours have passed since you r child missed a dose, either morning or evening, give the forgotten dose as soon as possible. Then go back to your usual schedule.
• If more than 6 hours have passed:
• If you r child missed a morning dose of Kaftrio, give it as soon as you remember. D o not give the evening dose of ivacaftor . Give t he next morning dose at the usual time.
• If you r child missed an evening dose of ivacaftor, do not give the missed dose. Wait for the next day and take the morning dose of Kaftrio as usual.

Do not give a double dose to make up for any missed doses.

If you stop giving your child Kaftrio Give Kaftrio to your child for as long as your child’s doctor recommends. Do not stop unless your child’s doctor advises you to.

If you have any further questions on the use of this medic ine, ask your child’s doctor or pharmacist.

❗ 4. Possible side effects

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

107 Serious side effects:

Possible signs of liver problems Liver damage and worsening of liver function in people with or without liver disease. The worsening of liver function can be serious and may require transplantation (see section 2) .

Increased liver enzymes in the blood are very common in patients treated with Kaftrio . These may be sign s of liver problems:

• Pain or discomfort in the upper right area of the stomach (abdominal) area
• Yellowing of the skin or the white part of the eyes
• Loss of appetite
• Nausea or vomiting
• Dark urine Depression. Signs of this include sad or altered mood, anxiety, feelings of emotional discomfort (see section 2).

Tell your child’s doctor straight away if he/she have any of these symptoms.

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

• Rash (more common in children, and in women compared to men) Tell your child’s doctor straight away if you notice a rash.

Other side effects

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

• Headache
• Dizziness
• Upper respiratory tract infection (common cold)
• Oropharyngeal pain ( sore throat )
• Nasal congestion
• Stomach or abdominal pain
• Diarrhoea
• Increased liver enzymes (signs of stress on the liver)
• Changes in the type of bacteria in mucus
• Increased creatine phosphokinase (sign of muscle breakdown) seen in blood tests

Common (may affect up to 1 in 10 people)

• Flu
• Abnormal breathing (s hortness of breath or difficulty breathing)
• Low blood sugar (hypoglycaemia)
• Runny nose
• Sinus problems (sinus congestion)
• Redness or soreness in the throat
• Ear problems: ear pain or discomfort, ringing in the ears, inflamed eardrum
• Spinning sensation (inner ear disorder)
• Wind (flatulence)
• Spots (acne)
• Itchy skin
• Breast mass
• Feeling nauseous

Uncommon (may affect up to 1 in 100 people)

• Breast and nipple problems: inflammation, pain
• Enlargement of the breast in men
• Increases in blood pressure
• Wheezing
• Blocked ears (ear congestion)

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

• Allergic reactions (hypersensitivity)
• Damage to the liver (liver injury)
• Raised bilirubin measurement (liver blood test)
• Behaviour al changes Additional s ide effects in adolescents Side effects in adolescents are similar to those observed in adults.

Additional side effects in children

Most cases of behavioural changes have been reported in younger children aged 2-5 years.

Reporting of side effects

If you r child gets any side effects, talk to your child’s 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. How to store Kaftrio

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 outer carton and on the sachet 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 wastew ater or household waste. Ask your child’s pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.

📦 6. Contents of the pack and other information

What Kaftrio contains

• The active substances are ivacaftor , tezacaftor and elexacaftor .

Kaftrio 60 mg/40 mg/80 mg granules Each sachet contains 60 mg of ivacaftor , 40 mg of tezacaftor and 80 mg of elexacaftor .

Kaftrio 75 mg/50 mg/100 mg granules Each sachet contains 75 mg of ivacaftor , 50 mg of tezacaftor and 100 mg of elexacaftor.

109 • The other ingredients are: silica colloidal anhydrous (E551) , croscarmellose sodium (E468) , hypromellose (E464) , hypromellose acetate succinate, lactose monohydrate, magnesium stearate (E470b) , mannitol (E421) , sodium laurilsulfate (E487) , and sucralose (E955) .

See the end of section 2 for important information about the contents of Kaftrio .

What Kaftrio looks like and contents of the pack

Kaftrio 60 mg/40 mg/80 mg granules are white to off-white granules in a sealed sachet .

Kaftrio 75 mg/50 mg/100 mg granules are white to off -white granules in a sealed sachet .

Kaftrio is available in p ack size of 28 sachets (4 weekly wallets, each with 7 sachets).

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

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

Tel: + 34 91 7892800 110 Ελλάδα Vertex Φαρμακευτική Μονοπρόσωπη Ανώνυμη Εταιρία Τηλ: +30 (211) 2120535 Italia Vertex Pharmaceuticals (Italy) S.r.l.

Tel: +39 0697794000

This leaflet was last revised in

Other sources of information Detailed information on this medicine is available on the European Medicines Agency website: https://www.ema.europa.eu . There are also links to other websites abo ut rare diseases and treatments.

📄 Package Leaflet – official source

This article reproduces the information in the official package leaflet, as authorised in the European Union. You can consult the original document here: Product information Kaftrio (PDF, ec.europa.eu).

You can check this medicine at any time in the Union Register of medicinal products (EU number EU/1/20/1468).

⚠️ Important: This article is for information purposes only and does not replace medical advice or the package leaflet inside the medicine box. Read the leaflet carefully before use. For any questions about your treatment, talk to your doctor or pharmacist. If you experience side effects, tell your doctor or pharmacist and report them through your national reporting system.