Prospect: information for the patient

Kaftrio 37,5mg/25mg/50mg film-coated tablets

Kaftrio75mg/50mg/100mg film-coated tablets

ivacaftor/tezacaftor/elexacaftor

This medicine is subject to additional monitoring, which will speed up 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 starting to take this medicine, as it contains important information for you.

• Keep this prospect, as you may need to refer to it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed only for you, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience adverse effects, consult your doctor or pharmacist, even if they do not appear in this prospect. See section 4.

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 6or older who suffer from CF withat least one mutationF508delin 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 with ivacaftor) helps you breathe better by improving your lung function. You may also notice that you get sick less often or that it is easier for you to gain weight.

Do not takeKaftrio

• if you are allergictoivacaftor, tezacaftor, elexacaftor, orany of the other ingredients of this medication (listed in section6).

Consult your doctorand do not take the tablets if this is the case.

Warnings and precautions

• Consult your doctorif you have liver problemsor have had them in the past. Your doctor may need to adjust your dose.
• Your doctor will perform someblood tests to check how your liver isbefore 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 doctor immediatelyif you have 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 you (or someone taking this medication) experience any of the following symptoms that may be signs of depression: sadness or mood alteration, anxiety, emotional discomfort, or thoughts of self-harm or suicide.

• Consult your doctorif you have kidney problemsor have had them in the past.

• Consult your doctorbefore starting treatment with Kaftrio if you have receivedan organ transplant.

• Consult your doctorif you are using hormonal contraceptives, for example, women who use the birth control pill. This may mean you are more prone to skin rash while taking Kaftrio.

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

Childrenunder 6years

Do not give this medication to children under 6years old as the safety and efficacy of Kaftrio tablets in this age group are unknown.

Other medications andKaftrio

Inform your doctor or pharmacistif you are taking, have 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 doctor if you are taking any of the medications listed below. Your doctor may change the dose of one of the medications if you are 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.
• 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 foods or drinks containing grapefruit during treatment as they may increasethe adverse effects of Kaftrio by increasing the amount of Kaftrio in the body.

Pregnancy and breastfeeding

• Consult your doctorbefore usingthis medication if you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant.
• Pregnancy:it may be best to avoid using this medication during pregnancy. Your doctor will help you decide what is best for you and your child.
• Breastfeeding:ivacaftor, tezacaftor, and elexacaftor are excreted in breast milk. Your doctor will consider the benefits of breastfeeding for your baby and the benefits of treatment for you to help you decide whether to stop breastfeeding or stop treatment.

Driving and operating machinery

Kaftrio may cause dizziness. If you feel dizzy, do not drive, ride a bike, or operate machinery unless you are sure it will not affect you.

Kaftrio contains sodium

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

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

Your doctor will determine the correct dose for you.

Kaftrio is usually taken with ivacaftor.

Recommended dose for patients 6 years or older

Take the morning and evening tablets with an interval of about 12hours.

The tablets are taken orally.

Take the Kaftrio and ivacaftor tablets with foods that contain fats.Meals or snacks that contain fats are those prepared with butter or oils or those that contain eggs. Examples of other foods that contain fats are:

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

Avoid meals and drinks that contain grapefruit while taking Kaftrio. SeeTaking Kaftrio with food and drinksin section2 for more information.

Swallow the tablets whole.Do not chew, crush, or break the tablets before swallowing.

You should continue taking all other medications, unless your doctor tells you to stop taking them.

If you have liver problems,whether moderate or severe, your doctor may reduce your dose of tablets or decide to suspend treatment with Kaftrio. SeeWarnings and precautionsin section2.

If you take moreKaftriothan you should

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

If you forget to takeKaftrio

If you forget a dose, calculate how much time has passed since the time you were supposed to take the dose.

• Ifless than 6hourshave passed since the time you were supposed to take the dose, whether it was the morning or evening dose, take the missed tablet or tablets as soon as you remember. Then continue with your regular schedule.

• Ifmore than 6hourshave passed:
• Ifyou forgotthe morningdose ofKaftrio, take it as soon as you remember.Do not take the evening dose of ivacaftor. Take the next morning dose of Kaftrio at the usual time.
• Ifyou forgotthe eveningdose of ivacaftor, do not take the missed dose. Wait until the next day and take the morning dose of Kaftrio at the usual time.

Do nottake a double dose to make up for the missed tablets.

If you interrupt treatment withKaftrio

Your doctor will tell you for how long you need to take Kaftrio. It is essential to take this medication consistently. Do not make changes unless your doctor tells you to.

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

Like all medicines, this medicine can 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 common 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 doctor immediatelyif you 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 doctor immediatelyif you 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.
• 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 injury).
• 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

If you experience any type of side effect, consult your 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. By doing so, you will help protect the environment.

Composition ofKaftrio

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

Kaftrio 37,5mg/25mg/50mg film-coated tablets

Each film-coated tablet contains 37.5mg of ivacaftor, 25mg of tezacaftor, and 50mg of elexacaftor.

Kaftrio75mg/50mg/100mg film-coated tablets

Each film-coated tablet contains 75mg of ivacaftor, 50mg of tezacaftor, and 100mg of elexacaftor.

• The other components are:

• Tablet core: hypromellose (E464), acetate succinate of hypromellose, sodium lauryl sulfate (E487), sodium croscarmellose (E468), microcrystalline cellulose (E460(i)), and magnesium stearate (E470b).
• Tablet coating: hypromellose (E464), hydroxypropyl cellulose (E463), titanium dioxide (E171), talc (E553b), yellow iron oxide (E172), and red iron oxide (E172).

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

Appearance of the product and contents of the pack

Kaftrio37,5mg/25mg/50mgfilm-coated tablets are orange-yellow capsules with the imprint “T50” on one side and smooth on the other.

Kaftrio75mg/50mg/100mg film-coated tablets are orange capsules with the imprint “T100” on one side and smooth on the other.

Kaftrio is available in pack sizes of 56film-coated tablets (4 blister packs of 14film-coated tablets 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 Person

Almac Pharma Services (Ireland) Limited

Finnabair Industrial Estate

Dundalk

Co. Louth

A91 P9KD

Ireland

Almac Pharma Services Limited

Seagoe Industrial Estate

Craigavon

County Armagh

BT63 5UA

United Kingdom (Northern Ireland)

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

Date of the last revision of this leaflet:

Other sources of information

The detailed information on this medicinal product isavailable on the website of the European Medicines Agency:https://www.ema.europa.eu.There are also links to other websites on rare diseases and orphan medicinal products.