Alyftrek 50 mg/20 mg/4 mg film-coated tablets and 125 mg/50 mg/10 mg film-coated tablets

Package leaflet: Information for the patient

Alyftrek 50 mg/20 mg/4 mg film-coated tablets

Alyftrek 125 mg/50 mg/10 mg film-coated tablets

deutivacaftor/tezacaftor/vanzacaftor

This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for how to report side effects.

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

·          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.

What is in this leaflet

1.   What Alyftrek is and what it is used for

2.   What you need to know before you take Alyftrek

3.   How to take Alyftrek

4.   Possible side effects

5.   How to store Alyftrek

6.   Contents of the pack and other information

1.      What Alyftrek is and what it is used for

Alyftrek is a tablet that contains three active substances: deutivacaftor, tezacaftor, and vanzacaftor.

Alyftrek is for people aged 6 years and over who have CF with at least one mutation in the CFTR (cystic fibrosis transmembrane conductance regulator) gene that is responsive to Alyftrek. Cystic fibrosis (CF) is an inherited condition in which the lungs and the digestive system can become clogged with thick, sticky mucus. Alyftrek is intended as a long-term treatment.

Alyftrek works on a protein called CFTR. The protein is damaged in some people with CF, if they have a mutation in the CFTR gene. Vanzacaftor and tezacaftor increase the amount of CFTR protein at the cell surface, while deutivacaftor causes the protein to work better.

Alyftrek helps your breathing by improving your lung function. You may also notice that you do not get ill as often, or that it is easier to gain weight.

2.      What you need to know before you take Alyftrek

Do not take Alyftrek

·      If you are allergic to deutivacaftor, tezacaftor, vanzacaftor or any of the other ingredients of this medicine (listed in section 6).

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

Warnings and precautions

·          Liver damage and worsening liver function in people with and without liver disease has been seen in some patients taking ivacaftor/tezacaftor/elexacaftor, a medicine that has the same or similar ingredients as Alyftrek. The worsening of liver function can be serious and may require transplantation.

·           Talk to your doctor if you have liver problems, or have had them previously.

Your doctor will do some blood tests to check your liver before and during treatment with Alyftrek, especially if your blood tests showed high liver enzymes in the past. Increased liver enzymes in the blood are common in patients with CF, and those taking Alyftrek. 

Tell your doctor right away if you have any signs of liver problems. These are listed in section 4.

·           Depression and anxiety have been reported in patients while taking Alyftrek. Changes in behaviour and sleep disorders have been reported in some patients taking ivacaftor/tezacaftor/elexacaftor, a medicine that has the same or similar ingredients as Alyftrek. Talk to your doctor straight away if you (or someone taking this medicine) experience any of the following symptoms which may be signs of depression or other psychiatric disorders: sad or altered mood, anxiety, feelings of emotional discomfort or thoughts of harming or killing yourself, sleep difficulties, and/or abnormal behaviour (see section 4).

·           Talk to your doctor if you have kidney problems, or you have previously had them.

·           If you have two Class I mutations (mutations known not to make CFTR protein), you should not take Alyftrek, as you are not expected to respond to this medicine.

·           Talk to your doctor before starting treatment with Alyftrek if you have received an organ transplant.

·           Talk to your doctor if you have taken another product with tezacaftor or ivacaftor before and temporarily or permanently stopped because of side effects. Your doctor may want to see you more often.

·           Talk to your doctor if you are using hormonal contraception (birth control) – for example, women using the contraceptive pill. This may mean you are more likely to get a rash while taking Alyftrek. Talk to your doctor if you develop a rash while taking Alyftrek.

·           Your doctor may do eye examinations before and during treatment with Alyftrek. Cloudiness of the eye lens (cataract) without any effect on vision has occurred in some children and adolescents receiving ivacaftor which is similar to deutivacaftor, one of the active substances in Alyftrek.

Children under 6 years of age

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

Other medicines and Alyftrek

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Some medicines can affect how Alyftrek 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 these 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.

·      Seizure 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 and glipizide.

·      Medicines for lowering blood pressure. These include verapamil.

Alyftrek with food and drink

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

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

·      Pregnancy: Your doctor will help you decide what is best for you and your child.

·      Breast-feeding: Tezacaftor has been detected in breastfed babies. There is insufficient information to determine if vanzacaftor or deutivacaftor passes into breast milk; however, ivacaftor has been detected in breastfed babies. 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.

Driving and using machines

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

Alyftrek contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium free’.

3.      How to take Alyftrek

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Alyftrek tablets come in two different strengths. Your doctor will determine the correct dose for you.

Recommended dose for people aged 6 years and older:

Weight Less than 40 kg Dose per day Three round-shaped tablets, once a day Tablet strength deutivacaftor 50 mg/tezacaftor 20 mg/vanzacaftor 4 mg

Weight 40 kg or more Dose per day Two capsule-shaped tablets, once a day Tablet strength deutivacaftor 125 mg/tezacaftor 50 mg/ vanzacaftor 10 mg

Take Alyftrek 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 Alyftrek. See Alyftrek with food and drink in section 2 for more details.

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

Take at approximately the same time each day. The tablets are for oral use.

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

If you have moderate liver problems, this medicine is not recommended but your doctor will decide if it is appropriate for you to take this medicine.

If you have severe liver problems, you should not be taking this medicine. See also Warnings and precautions in section 2.

If you take more Alyftrek than you should

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 to take Alyftrek

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, take the forgotten tablets as soon as possible. Then go back to your usual schedule.

·      If more than 6 hours have passed since the missed dose, skip the missed dose, and continue on the original schedule the next day.

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

If you stop taking Alyftrek

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

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4.      Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Serious side effects

Possible signs of liver problems

Increased liver enzymes in the blood are common in people with CF, and those taking Alyftrek. 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

Depression. Signs of this include sad or altered mood, anxiety, feelings of emotional discomfort.

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

Other side effects

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

·           Increase in liver enzymes (signs of stress on the liver)

·           Headache

·           Diarrhoea

·           Belly (abdominal) pain

·           Blocked nose (nasal congestion)

·           Upper respiratory tract (nose and throat) infection

·           Flu (influenza)

·           Redness or soreness in the throat (oropharyngeal pain)

·           Dizziness

·           Bacteria in sputum

Common (may affect up to 1 in 10 people)

·           Depression

·           Rash

·           Increase creatine phosphokinase (sign of muscle breakdown) seen in blood tests

·           Anxiety

·           Runny nose (rhinitis)

·           Ear pain

·           Ear discomfort

·           Redness of the throat (pharyngeal erythema)

·           Ringing or buzzing in the ears (tinnitus)

·           Increased blood flow to the eardrum which can cause redness and inflammation (tympanic membrane hyperaemia)

·           Problems with the nerves in the inner ear which can affect hearing and balance (vestibular disorder)

·           Sinus problems (sinus congestion)

·           Nausea (feeling sick)

·           Breast lumps (breast mass)

Uncommon (may affect up to 1 in 100 people)

·           Breast inflammation

·           Blocked ear (ear congestion)

·           Enlargement of the breast in men (gynaecomastia)

·           Problems with the nipple

·           Nipple pain

Reporting of side effects

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 national reporting system

HPRA Pharmacovigilance

Website: www.hpra.ie

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

5.      How to store Alyftrek

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 package after EXP. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6.      Contents of the pack and other information

What Alyftrek contains

·          The active substances are deutivacaftor, tezacaftor and vanzacaftor.

Alyftrek 50 mg/20 mg/4 mg film-coated tablets

Each film‑coated tablet contains 50 mg of deutivacaftor, 20 mg of tezacaftor and vanzacaftor calcium dihydrate equivalent to 4 mg of vanzacaftor.

Alyftrek 125 mg/50 mg/10 mg film-coated tablets

Each film‑coated tablet contains 125 mg of deutivacaftor, 50 mg of tezacaftor and vanzacaftor calcium dihydrate equivalent to 10 mg of vanzacaftor.

The other ingredients are:

·      Tablet core: croscarmellose sodium (E468), hypromellose (E464), hypromellose acetate succinate, magnesium stearate (E470b), microcrystalline cellulose (E460(i)) and sodium laurilsulfate (E487).

·      Tablet film coat: Carmine (E120), Brilliant Blue FCF aluminum lake (E133), hydroxypropyl cellulose (E463), hypromellose (E464), iron oxide red (E172), talc (E553b) and titanium dioxide (E171).

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

What Alyftrek looks like and contents of the pack

Alyftrek 50 mg/20 mg/4 mg film‑coated tablets are purple, round-shaped tablet debossed with “V4” on one side and plain on the other.

Alyftrek 125 mg/50 mg/10 mg film-coated tablets are purple, capsule-shaped tablet debossed with “V10” on one side and plain on the other.

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

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien България, Česká republika, Danmark, Deutschland, Eesti, France, Hrvatska, Ireland, Ísland, Κύπρος, Latvija, Lietuva, Luxembourg/Luxemburg, Magyarország, Malta, Nederland, Norge, Österreich, Polska, Portugal, România, Slovenija, Slovenská republika, Suomi/Finland, Sverige

Vertex Pharmaceuticals (Ireland) Limited

Tél/Tel/Teл/Tlf/Sími/Τηλ/Puh:

+353 (0) 1 761 7299

España

Vertex Pharmaceuticals Spain, S.L.

Tel: + 34 91 7892800

Ελλάδα

Vertex Φαρμακευτική Μονοπρόσωπη Ανώνυμη Εταιρία

Τηλ: +30 (211) 2120535

Italia

Vertex Pharmaceuticals

(Italy) S.r.l.

Tel: +39 0697794000

This leaflet was last revised in 06/2025.

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site: https://www.ema.europa.eu/en. There are also links to other websites about rare diseases and treatments.