KAFTRIO 60 mg/40 mg/80 mg granules in sachet

2. What you need to know before your child takes Kaftrio

Do not giveKaftrio to your child

• to ivacaftor, tezacaftor, elexacaftor, or any of the other ingredients of this medicine (listed in section 6).

Talk to your child's doctorand do not give this medicine if this applies to your child.

Warnings and precautions

• Talk to your child's doctorif your child has liver problemsor has had them in the past. The doctor may need to adjust the dose.

• The doctor will do some blood tests on your child to check how their liver is workingbefore and during treatment with Kaftrio, especially if blood tests have shown elevated liver enzymes in the past. Liver enzymes in the blood may increase in patients taking Kaftrio.

Tell your child's doctor immediatelyif your child has any symptoms that may indicate liver problems. These are listed in section 4.

Depression (including suicidal thoughts and behaviors) has been reported in patients taking Kaftrio, usually starting in the first three months of treatment.

• Talk to your doctor immediately if your child has any of the following symptoms, which may be signs of depression: sadness or mood changes, anxiety, feeling emotionally unwell, or thoughts of self-harm or suicide.

• Talk to your child's doctorif your child has kidney problemsor has had them in the past.

• Talk to your child's doctorbefore starting treatment with Kaftrio if your child has had an organ transplant.

• Your child's doctor may doeye examinationsbefore and during treatment with Kaftrio. In some children and adolescents who have taken this treatment, cataracts (clouding of the lens in the eye) have occurred without affecting vision.

Children under 2years

Do not give Kaftrio granules to children under 2 years, as it is not known if Kaftrio granules are safe and effective in this age group.

Other medicines andKaftrio

Tell your child's doctor or pharmacistif your child is taking, has recently taken, or might take any other medicines. Some medicines may affect how Kaftrio works or may increase the chance of side effects. In particular, talk to your child's doctor if your child is taking any of the following medicines. The doctor may need to change the dose of one of the medicines if your child is taking some of these.

• Antifungals(used to treat fungal infections). These include fluconazole, itraconazole, ketoconazole, posaconazole, and voriconazole.
• Antibiotics(used to treat bacterial infections). These include clarithromycin, erythromycin, rifampicin, rifabutin, and telithromycin.
• Medicines for epilepsy(used to treat seizures or fits). These include carbamazepine, phenobarbital, and phenytoin.
• Herbal products. These include St. John's Wort (Hypericum perforatum).
• Immunosuppressants(used after an organ transplant). 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, glipizide, gliburide, nateglinide, and repaglinide.
• Medicines to lower cholesterol. These include pitavastatin and rosuvastatin.
• Medicines to lower blood pressure. These include verapamil.

TakingKaftrio withfood and drinks

Avoid giving your child foods or drinks that contain grapefruit during treatment, as they may increase the risk of side effects of Kaftrio. See Taking Kaftrio with food and drinksin section 2 for more information.

Driving and using machines

Kaftrio may make your child feel dizzy. If your child feels dizzy, it is recommended that they do not ride a bicycle or perform any activity that requires their full attention.

Kaftrio granules contain lactose and sodium

If your child's doctor has told your child that they have an intolerance to some sugars, talk to the doctor before your child takes this medicine.

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

3. How to take Kaftrio

Always follow the instructions of your child's doctor or pharmacist for taking this medicine. If you are not sure, talk to your child's doctor or pharmacist again.

The doctor will decide the correct dose for your child. Your child should keep taking all their other medicines unless the doctor tells them to stop taking one.

Kaftrio is usually taken with ivacaftor.

Recommended dose for patients aged 2years to less than 6years

Give your child the morning and evening doses with a gap of about 12 hours.

The granules are taken by mouth.

Preparing Kaftrio granules:

• Hold the sachet with the tear line facing upwards.
• Gently shake the sachet to settle the Kaftrio granules.
• Open the sachet by tearing or cutting along the tear line.
• Carefully pour all the granules from the Kaftrio sachet into 1 teaspoon (5 ml) of soft food or liquid in a small container (such as an empty bowl).

• The food or liquid should be at room temperature or below.
• Some examples of soft foods or liquids include fruit puree, flavored yogurt or pudding, and milk or juice.

• Mix the Kaftrio granules with food or liquid.

Once mixed, give the Kaftrio within 1 hour. Make sure your child takes all the medicine.

Give the doses of Kaftrio and ivacaftor withfat-containing foods. Fat-containing meals or snacks are those prepared with butter or oils or those that contain eggs. Examples of 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, bars or nutritional drinks that contain fat

Avoid giving your child foods or drinks that contain grapefruit while taking Kaftrio. See Taking Kaftrio with food and drinksin section 2 for more information.

If your child has liver problems,the doctor may reduce the dose of the medicine or decide to stop the treatment with Kaftrio. See Warnings and precautionsin section 2.

If your child takes moreKaftriothan they should

Talk to your child's doctor or pharmacist.If possible, take your child's medicine and this leaflet with you. Your child may experience side effects, including those listed in section 4 below.

If you forget to giveKaftrio to your child

If you forget to give a dose to your child, work out how long it is since the dose was supposed to be given.

• Ifit has been less than 6hourssince the time your child was supposed to take the dose, give the missed dose as soon as possible. Then continue with the usual schedule.

• Ifit has been more than 6hours:
• If your child missesa morning doseof Kaftrio, give it as soon as you remember. Do not give the evening dose of ivacaftor. Give the next morning dose at the usual time.
• If your child missesan evening dose of ivacaftor, do not give the missed dose. Wait until the next morning and give the morning dose of Kaftrio at the usual time.

Do notgive a double dose to make up for missed doses.

If you stop treatment withKaftrio for your child

Give Kaftrio to your child for as long as the doctor has recommended. Do not stop treatment unless the doctor tells you to.

If you have any other questions about the use of this medicine, 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.

Serious side effects

Signs of liver problems

Liver damage and worsening of liver functionin people with severe liver disease. Worsening of liver function can be severe and may require a transplant.

Increased liver enzymes in the blood are common in patients with CF. The following may be signs of liver problems:

• Pain or discomfort in the upper right side of the stomach (abdominal area).
• Yellowing of the skin or the white part of the eyes.
• Loss of appetite.
• Feeling sick (nausea) or being sick (vomiting).
• Dark-colored urine.

Depression.Signs include feeling sad or having mood changes, anxiety, feeling emotionally unwell.

Tell your child's doctor immediatelyif your child has any of these symptoms.

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

• Rash (more common in females than males).

Tell your child's doctor immediatelyif your child has a rash.

Other side effectsseen with Kaftrio:

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

• Headache.
• Dizziness.
• Infection of the upper respiratory tract (common cold).
• Sore throat.
• Blocked nose.
• Stomach (abdominal) pain.
• Diarrhea.
• Increased liver enzymes (signs of liver stress).
• Changes in the type of bacteria in the mucus.
• Increased creatine phosphokinase (sign of muscle breakdown), seen in blood tests.

Common(may affect up to 1 in 10 people)

• Flu.
• Abnormal breathing (shortness of breath or difficulty breathing).
• Low blood sugar (hypoglycemia).
• Runny nose.
• Sinus problems (sinus congestion).
• Sore or painful throat.
• Ear problems: ear pain or discomfort, ringing in the ears, inflamed eardrum.
• Feeling like everything is spinning (inner ear disorder).
• Wind (flatulence).
• Spots (acne).
• Itchy skin.
• Lump in the breast.
• Feeling sick (nausea).

Uncommon(may affect up to 1 in 100 people)

• Breast or nipple problems: inflammation, pain.
• Increased breast size in males.
• Increased blood pressure.
• Wheezing.
• Blocked ears (ear congestion).

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

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

Additional side effectsin adolescents

The side effects seen in adolescents are similar to those seen in adults.

Reporting of side effects

If your child experiences any side effects, talk to your child's doctor or pharmacist, even if they are not listed in this leaflet. You can also report side effects directly through 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. Storage of 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 carton and sachet after EXP. The expiry date is the last day of the month shown.

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. This will help protect the environment.

6. Package Contents and Additional Information

Composition ofKaftrio

• The active ingredients 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.

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

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

Appearance and Package Contents

Kaftrio 60 mg/40 mg/80 mg granules are white to off-white, sweet-tasting, and flavorless granules contained in a sealed sachet.

Kaftrio 75 mg/50 mg/100 mg granules are white to off-white, sweet-tasting, and flavorless granules contained in a sealed sachet.

Kaftrio is available in pack sizes of 28 sachets (4 weekly wallets with 7 sachets each).

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

Northern Ireland BT63 5UA

United Kingdom

You can request more information about this medicinal product by contacting 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.