Kaftrio 75 mg/50 mg/100 mg granules in sachet

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

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

Kaftrio 75mg/50mg/100mg granules in sachet

ivacaftor/tezacaftor/elexacaftor

Read the entire leaflet carefully before your child starts taking this medicine, because it contains important information for your child.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your child's doctor or pharmacist.
• This medicine has been prescribed for your child only; do not give it to other people, even if they have the same symptoms as your child, as it may harm them.
• If your child experiences any adverse effects, consult your child's doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Kaftrio is and what it is used for

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

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

Kaftrio acts on a protein called CFTR. This protein is defective in some people with CF if they have a mutation in the CFTR gene.

Kaftrio is usually taken with another medicine, ivacaftor. Ivacaftor improves the function of the protein, while tezacaftor and elexacaftor increase the amount of protein at the cell surface.

Kaftrio (taken together with ivacaftor) helps your child breathe better by improving their lung function. You may also notice that your child does not get sick as often or that it is easier for them to gain weight.

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

Do not give Kaftrio to your child

• if your child is allergic to ivacaftor, tezacaftor, elexacaftor, or to any of the other components of this medicine (listed in section 6).

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

Warnings and precautions

• Talk to your child's doctor if your child has liver problems or has had them before. Your child's doctor may need to adjust the dose (see section 4).

• Your doctor will perform some blood tests on your child to monitor liver function before and during treatment with Kaftrio, especially if blood tests previously showed elevated liver enzymes. Liver enzymes in the blood may increase in patients receiving Kaftrio.

Tell your child's doctor immediately if your child experiences any symptoms indicating liver problems. These are listed in section 4.

• Depression (including suicidal thoughts, changes in behavior, anxiety, and sleep disorders) has been reported in patients taking Kaftrio, usually beginning within the first three months of treatment. Contact your doctor immediately if your child experiences any of the following symptoms, which may be signs of depression: sadness or mood changes, anxiety, feelings of emotional distress, thoughts of self-harm or suicide, and/or difficulty sleeping (see section 4).

Talk to your doctor if you notice behavioral changes in your child during the first 2 months of treatment.

• Talk to your child's doctor if your child has kidney problems or has had them before.

• If your child has two class I mutations (mutations known not to produce the CFTR protein), Kaftrio should not be taken, as a response to this medicine is not expected.

• Talk to your child's doctor before starting treatment with Kaftrio if your child has received an organ transplant.

• Your child's doctor may perform eye examinations before and during treatment with Kaftrio. In some children and adolescents receiving this treatment, lens opacities (cataracts) have occurred without affecting vision.

Children under 2 years of age

Do not give Kaftrio granules to children under 2 years of age, as it is unknown whether 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 need to take any other medicines. Some medicines may affect how Kaftrio works or may increase the likelihood of side effects. In particular, talk to your child's doctor if your child is taking any of the following medicines. Your child's doctor may need to adjust the dose of one of the medicines if your child is taking any of these.

• Antifungals (used to treat infections caused by fungi). These include fluconazole, itraconazole, ketoconazole, posaconazole, and voriconazole.
• Antibiotics (used to treat infections caused by bacteria). These include clarithromycin, erythromycin, rifampicin, rifabutin, and telithromycin.
• Medicines for epilepsy (used to treat seizures or epileptic fits). 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, glipizide, glyburide, nateglinide, and repaglinide.
• Medicines to lower blood cholesterol. These include pitavastatin and rosuvastatin.
• Medicines to lower blood pressure. These include verapamil.

Taking Kaftrio with food and drinks

Avoid giving your child food or drinks containing grapefruit during treatment, as they may increase the side effects of Kaftrio by increasing the amount of Kaftrio in your child's body.

Driving and using machines

Kaftrio may cause dizziness in your child. If your child feels dizzy, it is recommended that they avoid riding a bicycle or performing any activity that requires full attention.

Kaftrio granules contain lactose and sodium

If your child's doctor has informed you that your child has an intolerance to certain sugars, consult with the doctor before your child takes this medicine.

This medicine contains less than 23 mg of sodium (1 mmol) per dose unit; this means it is essentially “sodium-free”.

3. How to take Kaftrio

Follow exactly the instructions for administering this medicine given by your child's doctor or pharmacist. If in doubt, consult your child's doctor or pharmacist again.

Your child's doctor will determine the correct dose for your child. Your child should continue taking all other medications, unless your child's doctor instructs otherwise.

Kaftrio is usually taken together with ivacaftor.

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

Administer the morning and evening doses to your child approximately 12 hours apart.

The granules are taken orally.

Preparation of Kaftrio granules:

• Hold the sachet with the cut line facing upwards.

• Gently shake the sachet so that the Kaftrio granules settle.

• Open the sachet by tearing or cutting along the cut 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). Make sure no granules remain inside the sachet.

• The food or liquid should be at room temperature or cooler.

• Examples of suitable soft foods or liquids include fruit puree, flavoured yoghurt or pudding, and milk or juice.

• Mix Kaftrio granules with food or liquid.

Once mixed, administer Kaftrio within 1 hour. Ensure that all the medication is taken.

Administer doses of Kaftrio and ivacaftor with food containing fat. Meals or snacks containing fat include those prepared with butter or oils, or those containing eggs. Other examples of fatty foods include:

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

Avoid giving your child grapefruit-containing foods or drinks while taking Kaftrio. See Taking Kaftrio with food and drinks in section 2 for more information.

If your child has liver problems, whether moderate or severe, your child's doctor may reduce the dose of the medicine or decide to stop treatment with Kaftrio. See Warnings and precautions in section 2.

If your child takes more Kaftrio than they should

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

If you forgot to give Kaftrio to your child

If you forget to give your child a dose, consider how much time has passed since the missed dose was due.

• If less than 6 hours have passed since the time your child should have taken the dose, either in the morning or evening, give the missed dose as soon as possible. Then continue with the usual dosing schedule.

• If more than 6 hours have passed:

  • If your child missed a morning dose of 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 missed an evening dose of ivacaftor, do not give the missed dose. Wait until the next day and give the morning dose of Kaftrio at the usual time.

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

If you stop your child's treatment with Kaftrio

Give Kaftrio to your child for as long as your child's doctor has recommended. Do not stop treatment unless instructed by your child's doctor.

If you have any further questions about the use of this medicine, ask your child's doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Serious adverse effects:

Possible signs of liver problems

Liver damage and worsening of liver function in people with or without pre-existing liver disease. Worsening of liver function can be severe and may require a liver transplant (see section 2).

Increased liver enzymes in the blood are very common in patients treated with Kaftrio. 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 the whites of the eyes.
• Loss of appetite.
• Nausea or vomiting.
• Dark-colored urine.

Depression. Signs include sadness or mood changes, anxiety, and feelings of emotional distress (see section 2).

Contact your child’s doctor immediately if any of these symptoms occur.

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

• Rash (more common in children and women than in men).

Contact your child’s doctor immediately if a skin rash occurs.

Other adverse 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.
• Diarrhea.
• Increased liver enzymes (signs of liver stress).
• Changes in the types of bacteria in mucus.
• Increased creatine phosphokinase (sign of muscle breakdown), observed in blood tests.

Common (may affect up to 1 in 10 people)

• Influenza (flu).
• Abnormal breathing (shortness of breath or difficulty breathing).
• Low blood sugar (hypoglycemia).
• Runny nose.
• Sinus problems (sinus congestion).
• Redness or soreness of the throat.
• Ear problems: ear pain or discomfort, ringing in the ears, inflamed eardrum.
• Sensation of spinning (inner ear disorder).
• Flatulence (gas).
• Skin pimples (acne).
• Itchy skin.
• Lump in the breast.
• Nausea.

Uncommon (may affect up to 1 in 100 people)

• Breast or nipple problems: swelling, pain.
• Enlargement of the breasts in males.
• Increases in blood pressure.
• Wheezing.
• Ear blockage (ear congestion).

Frequency not known (cannot be estimated from available data)

• Allergic reactions (hypersensitivity).
• Liver damage (hepatic injury).
• Increased bilirubin (liver blood test).
• Changes in behavior.

Additional adverse effects in adolescents

Adverse effects observed in adolescents are similar to those observed in adults.

Additional adverse effects in children

Most cases of behavioral changes have been reported in young children aged 2 to 5 years.

Reporting of adverse effects

If your child experiences any adverse effects, consult your child’s doctor or pharmacist, even if they are possible adverse effects not listed in this leaflet. You may also report them directly through the national reporting system included in Appendix V. By reporting adverse 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 stated on the carton and on the sachet after EXP. The expiry date is the last day of the month indicated.

This medicine requires no special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Pack contents and other information

Composition of Kaftrio

• 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.

• The other components 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 on the contents of Kaftrio.

What Kaftrio looks like and contents of the pack

Kaftrio 60 mg/40 mg/80 mg granules is a white to off-white granular powder contained in a sealed sachet.

Kaftrio 75 mg/50 mg/100 mg granules is a white to off-white granular powder contained in a sealed sachet.

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

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

Date of the latest revision of this Patient Information Leaflet:

Other sources of information

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