Prospect: information for the patient

Kaftrio 60mg/40mg/80mg granulated in a sachet

Kaftrio75mg/50mg/100mg granulated in a sachet

ivacaftor/tezacaftor/elexacaftor

This medicine is subject to additional monitoring, which will expedite the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section 4 includes information on how to report these adverse effects.

Read this prospect carefully before your child starts taking this medicine, as it contains important information for your child.

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

1.What isKaftrioand what is it used for

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

3.How to take Kaftrio

4.Possible adverse effects

5.Storage of Kaftrio

6.Contents of the package and additional information

Kaftrio contains three active principles:ivacaftor, tezacaftor and elexacaftor. This medication helps lung cells function better in some patients with cystic fibrosis (CF). CF is a hereditary condition in which the lungs and digestive system can become obstructed with thick and sticky mucus.

Kaftrio taken with ivacaftor is forpatients aged 2years or less than 6years old who suffer from CF withF508delmutation in theCFTRgene (cystic fibrosis transmembrane conductance regulator).Kaftriois designed as a long-term treatment.

Kaftrio acts on a protein called CFTR. The protein is damaged in some people with CF, if they have a mutation in theCFTRgene.

Kaftrio is usually taken with another medication,ivacaftor. Ivacaftor makes the protein function better while tezacaftor and elexacaftor increase the amount of protein on the cell surface.

Kaftrio (taken together with ivacaftor) helps your child with breathing by improving their lung function. You may also notice that your child gets sick less often or that it is easier for them to gain weight.

Do not administerKaftrio to your child

• if your child is allergictoivacaftor, tezacaftor, elexacaftor orany of the other components of this medication (listed in section6).

Consult your child's doctorand do not give this medication to your child, if this is the case.

Warnings and precautions

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

• Your child's doctor will perform someblood tests to check how your child's liver is functioningbefore and during treatment with Kaftrio, especially if previous blood tests showed elevated liver enzymes. Liver enzymes in the blood may increase in patients taking Kaftrio.

Inform your child's doctor immediatelyif your child experiences any symptoms indicative of liver problems. These are listed in section4.

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

• Consult your doctor immediately if your child experiences any of the following symptoms, which may be signs of depression: sadness or mood changes, anxiety, emotional discomfort, or thoughts of self-harm or suicide.

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

• Consult your child's doctorbefore starting treatment with Kaftrio if your child has receivedan organ transplant.

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

Childrenunder 2 years

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

Other medications andKaftrio

Inform your child's doctor or pharmacistif your child is taking, has taken recently, or may need to take any other medication. Some medications may affect the functioning of Kaftrio or increase the likelihood of adverse effects. In particular, consult your child's doctor if your child is taking any of the following medications:

• 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.
• Seizure medications(used to treat seizures or epilepsy). These include carbamazepine, phenobarbital, and phenytoin.
• Herbal medications.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.
• Diabetes medications.These include glimepiride, glipizide, glibenclamide, nateglinide, and repaglinide.
• Cholesterol-lowering medications.These include pitavastatin androsuvastatin.
• Blood pressure-lowering medications. These include verapamil.

TakingKaftrio withfood and drinks

Avoid giving your child foods or drinks that contain grapefruit during treatment, as they may increasethe adverse effects of Kaftrio by increasing the amount of Kaftrio in your child's body.

Driving and operating machinery

Kaftrio maycause your child to feel dizzy. Ifyour child feels dizzy,it is recommended thatthey do not ride a bicycleor engage in any activity that requires their full attention.

Kaftrio granules contain lactose and sodium

Consult your child's doctor if your child has been diagnosed with a certain sugar intolerance before giving your child this medication.

This medicationcontainsless than23mg of sodium (1mmol)per dose; this is, essentially “sodium-free”.

Follow exactly the administration instructions of this medication as indicated by your child's doctor or pharmacist. In case of doubt, consult again with your child's doctor or pharmacist.your child's doctor or pharmacist..

Your child's doctor will determine the correct dose for your child. Your child should continue to use all other medications unless the doctor indicates that they should stop taking one.

Kaftrio is usually taken with ivacaftor.

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

Administer the morning and evening doses with an interval of approximately 12hours.

The granule is taken orally.

Kaftrio granule preparation:

• Hold the packet with the line for cutting upwards.
• Shake the packet gently so that Kaftrio granule settles.
• Open the packet by breaking or cutting along the line for cutting.
• Carefully pour all the granule from the Kaftrio packet into 1teaspoon (5ml) of soft food or liquid in a small container (such as an empty cup)

• The food or liquid must be at room temperature or below.
• Examples of soft foods or liquids include fruit puree, yogurt, pudding, milk, or juice.

• Mix Kaftrio granule with food or liquids.

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

Administer Kaftrio and ivacaftor doses with fatty foods.Meals or snacks that contain fat are those prepared with butter or oils or those that contain eggs. Examples of other foods that contain fat are:

• Dairy products, whole milk, whole milk products, yogurt, chocolate
• Meat, blue fish
• Avocado, hummus (chickpea puree), soy-based products (tofu)
• Nuts, bars, or nutritional beverages that contain fat

Avoid giving your child foods or drinks that contain grapefruit while taking Kaftrio. SeeKaftrio with foods and beveragesin section2 for more information.

If your child has liver problems, either moderate or severe, the doctor may reduce the dose of their medication or decide to suspend treatment with Kaftrio. SeeWarnings and precautionsin section2.

If your child takes moreKaftriothan they should

Consult the doctor or pharmacist.If possible, bring the child's medication and this leaflet. The child may experience adverse effects, including those listed in section4 below.

If you forgot to giveKaftrio to your child

If you forget to give a dose to your child, calculate how much time has passed since the scheduled dose time.

• Ifless than 6hourshave passed since the scheduled dose time, whether it was the morning or evening dose, give the missed dose as soon as possible. Then continue with the regular schedule.

• Ifmore than 6hourshave passed:
• If your child forgotthe 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 regular time.
• If your child forgotthe evening dose of ivacaftor,do not give the missed dose. Wait until the next day and give the morning dose of Kaftrio at the regular time.

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

If you interrupt the treatment withKaftrio

Administer Kaftrio to your child for the entire time recommended by the doctor. Do not interrupt treatment unless the doctor indicates so.

If you have any other questions about the use of this medication, ask the doctor or pharmacist.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

Severe side effects

Possible 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.

The increase in liver enzymes in the blood is frequent in patients with FQ. 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.
• Nausea or vomiting.
• Dark-colored urine.

Depression.The signs include sadness or mood alteration, anxiety, emotional discomfort.

Inform your child's doctor immediatelyif they experience any of these symptoms.

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

• Skin rash (more common in women than in men).

Inform your child's doctor immediatelyif they experience a skin rash.

Other side effectsobserved with Kaftrio:

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

• Headache.
• Dizziness.
• Upper respiratory tract infection (common cold).
• Pharyngitis (sore throat).
• Runny nose.
• Abdominal pain or discomfort.
• Diarrhea.
• Increased liver enzymes (signs of liver stress).
• Changes in the type of bacteria in mucus.
• Increased creatine phosphokinase (sign of muscle breakdown), observed in blood tests.

Common(may affect up to 1 in 10people)

• Influenza.
• Abnormal breathing (shortness of breath or difficulty breathing).
• Low blood sugar (hypoglycemia).
• Runny nose.
• Paranasal sinus problems (congestion of the paranasal sinuses).
• Redness or sore throat.
• Ear problems: ear pain or discomfort, ringing in the ears, inflamed eardrum.
• Vertigo (dizziness).
• Flatulence (gas).
• Acne (pimples).
• Itching skin.
• Breast lump.
• Nausea.

Uncommon(may affect up to 1 in 100people)

• Problems with breasts or nipples: inflammation, pain.
• Enlargement of breasts in men.
• Increased blood pressure.
• Wheezing.
• Eustachian tube blockage (congestion of the ears).

Frequency not known(cannot be estimated from available data)

• Liver damage (hepatic lesion).
• Increased bilirubin (liver enzyme analysis).

Additional side effectsin adolescents

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

Reporting of side effects

Ifyour childexperiences any type of side effect, consult your child's doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the box and on the blister pack afterEXP.The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. In this way, you will help protect the environment.

Composition ofKaftrio

• The active ingredients are ivacaftor, tezacaftor, and elexacaftor.

Kaftrio 60mg/40mg/80mg granule

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

Kaftrio75mg/50mg/100granule

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

• The other components are:colloidal anhydrous silica (E551), sodium croscarmellose (E468), hypromellose (E464), acetate succinate of hypromellose, lactose monohydrate,emagnesium 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 of the product and contents of the package

Kaftrio 60mg/40mg/80mg granule is a white to off-white granule, sweetened and flavorless, contained in a sealed sachet.

Kaftrio 75mg/50mg/100mg granule is a white to off-white granule, sweetened and flavorless, contained in a sealed sachet.

Kaftrio is available in package sizes of 28sachets (4weekly packs with 7sachets 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

Responsible for manufacturing

Almac Pharma Services (Ireland) Limited

Finnabair Industrial Estate

Dundalk

Co. Louth

A91 P9KD

Ireland

Almac Pharma Services Limited

Seagoe Industrial Estate

Craigavon

Northern IrelandBT63 5UA

UK

For more information about this medicine, please contact the local representative of the marketing authorization holder:

Last update of this leaflet:

Other sources of information

The detailed information about this medicine is available on the website of the European Medicines Agency:https://www.ema.europa.eu.There are also links to other websites about rare diseases and orphan medicines.