Kaftrio 75 mg/50 mg/100 mg film-coated tablets

• 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.

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

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

Talk to your doctor and do not take the tablets, if this applies to you.

• Talk to your doctor if you have liver problems, or have had them previously. Your doctor may need to adjust your dose.
• Your doctor will do some blood tests to check your liver before and during treatment with Kaftrio, especially if your 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 you have any symptoms of liver problems. These are listed in section 4.

• Talk to your doctor if you have kidney problems, or you have previously had them.
• Talk to your doctor before starting treatment with Kaftrio if you have received an organ transplant.
• Talk to your doctor if you are using hormonal contraception – for example, women using the contraceptive pill. This may mean you are more likely to get a rash while taking Kaftrio.
• Your 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.

Do not give this medicine to children under the age of 6 years because it is not known if Kaftrio is safe and effective in this age group.

Tell your doctor or pharmacist if you are taking, have 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 doctor if you take any of the medicines listed below. Your doctor may change the dose of one of the medicines if you take any of these.

• Antifungal medicines (used for the treatment of fungal infections). These include fluconazole, 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).
• 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.

Avoid food or drinks containing grapefruit during treatment as these may increase the side effects of Kaftrio by increasing the amount of Kaftrio in your body.

• Ask your doctor for advice before taking this medicine if you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby.
  • Pregnancy: It may be better to avoid using this medicine during pregnancy. Your doctor will help you decide what is best for you and your child.
  • Breast-feeding: It is not known if ivacaftor, tezacaftor or elexacaftor passes into breast milk. Your doctor will consider the benefit of breast-feeding for your baby and the benefit of treatment for you to help you decide whether to stop breast-feeding or to stop treatment.

Kaftrio can make you dizzy. If you feel dizzy, do not drive, cycle, or use machines unless you are not affected.

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

Age - 6 to <12 years, Weight - <30 kg, Morning dose - Two ivacaftor 37.5 mg/tezacaftor 25 mg/elexacaftor 50 mg tablets, Evening dose - One ivacaftor 75 mg tablet.

Age - 6 to <12 years, Weight - ≥30 kg, Morning dose - Two ivacaftor 75 mg/tezacaftor 50 mg/elexacaftor 100 mg tablets, Evening dose - One ivacaftor 150 mg tablet.

Age - ≥12 years, Morning dose - Two ivacaftor 75 mg/tezacaftor 50 mg/elexacaftor 100 mg tablets, Evening dose - One ivacaftor 150 mg tablet.

Take the morning and evening tablets about 12 hours apart.

The tablets are for oral use.

Take both Kaftrio and ivacaftor tablets 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 food and drink containing grapefruit while you are taking Kaftrio. See Kaftrio with food and drink in section 2 for more details.

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

You must keep using all your other medicines, unless your doctor tells you to stop.

If you have liver problems, either moderate or severe, your doctor may reduce the dose of your tablets or decide to stop treatment with Kaftrio. See also Warnings and precautions in section 2.

Contact your doctor or pharmacist for advice. If possible, take your medicine and this leaflet with you. You may get side effects, including those mentioned in section 4 below.

If you forget a dose, work out how long it is since the dose you missed.

• If less than 6 hours have passed since you missed a dose, either morning or evening, take the forgotten tablet(s) as soon as possible. Then go back to your usual schedule.
• If more than 6 hours have passed:
  • If you missed a morning dose of Kaftrio, take it as soon as you remember. Do not take the evening dose of ivacaftor. Take the next morning dose at the usual time.
  • If you missed an evening dose of ivacaftor, do not take the missed dose. Wait for the next day and take the morning dose of Kaftrio tablets as usual.

Do not take a double dose to make up for any missed tablets.

Your doctor will tell you how long you need to keep taking Kaftrio. It is important to take this medicine regularly. Do not make changes unless your doctor tells you.

Possible signs of liver problems

Liver damage and worsening of liver function in people with severe liver disease. The worsening of liver function can be serious and may require transplantation.

Increased liver enzymes in the blood are very common in patients treated with Kaftrio. These may be signs 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

Tell your doctor straight away if you have any of these symptoms.

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

• Rash (more common in women than in men)

Tell your doctor straight away if you notice a rash.

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

Common (may affect up to 1 in 10 people)

• Flu
• Abnormal breathing (Shortness 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
• Increased creatine phosphokinase (sign of muscle breakdown) seen in blood tests

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)

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

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the:

or search for MHRA Yellow Card in the Google Play or Apple App Store.

By reporting side effects you can help provide more information on the safety of this medicine.

• The active substances are ivacaftor, tezacaftor and elexacaftor.

Kaftrio 37.5 mg/25 mg/50 mg film-coated tablets

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

Kaftrio 75 mg/50 mg/100 mg film-coated tablets

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

• The other ingredients are:
  • Tablet core: Hypromellose (E464), hypromellose acetate succinate, sodium laurilsulfate (E487), croscarmellose sodium (E468), microcrystalline cellulose (E460(i)), and magnesium stearate (E470b).
  • Tablet film coating: Hypromellose (E464), hydroxypropyl cellulose (E463), titanium dioxide (E171), talc (E553b), iron oxide yellow (E172), and iron oxide red (E172).

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

Kaftrio 37.5 mg/25 mg/50 mg film-coated tablets are light orange, capsule-shaped tablets stamped with “T50” on one side and plain on the other.

Kaftrio 75 mg/50 mg/100 mg film-coated tablets are orange, capsule-shaped tablets stamped with “T100” on one side and plain on the other.

Kaftrio is available in pack size of 56 tablets (4 blister cards, each with 14 tablets).