Alyftrek

Package leaflet: Information for the patient

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

deutivacaftor/tezacaftor/vanzacaftor
Medicinal product subject to additional monitoring. This will allow rapid identification of
new safety information. You can help by reporting any side effects you experience while taking
this medicinal product. See the end of section 4 for information on how to report side effects.
Please 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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Alyftrek is and what it is used for
2. What you need to know before taking 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 containing three active substances: deutivacaftor, tezacaftor and vanzacaftor.
Alyftrek is intended for patients aged 6 years and older with cystic fibrosis (CF) who have at least one
mutation in the CFTR ( cystic fibrosis transmembrane conductance regulator ) gene that
responds to Alyftrek. Cystic fibrosis (CF) is an inherited disease in which the lungs and digestive
system can become blocked by thick, sticky mucus. Alyftrek is intended for long-term treatment.
Alyftrek acts on a protein called CFTR. This protein is defective in some people with CF who have a mutation in the CFTR gene. Vanzacaftor and tezacaftor increase the amount of CFTR protein on the cell surface, while deutivacaftor improves the function of the protein.
Alyftrek improves breathing by enhancing lung function. You may also notice that you get fewer infections or that it is easier to gain weight.

2. What you need to know before taking 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). Consult your doctor and do not take the tablets if this applies to you.

Warnings and precautions

• Liver damage and worsening of liver function, in people with or without liver disease, have been observed in some patients taking ivacaftor/tezacaftor/elexacaftor, a medicine with components similar to those of Alyftrek. Worsening of liver function can be severe and may require liver transplantation.
• Contact your doctor if you have liver problems or have had them in the past.

Your doctor will perform certain blood tests to monitor your liver function
before and during treatment with Alyftrek, especially if previous blood tests
showed high levels of liver enzymes. Elevated liver enzymes in the blood are
common in patients with CF and in those taking Alyftrek.
Inform your doctor immediately if you experience signs of liver problems. These are listed in
section 4.

• In some patients during treatment with Alyftrek, depression and anxiety have been reported. In some patients taking ivacaftor/tezacaftor/elexacaftor, a medicine with the same or similar active substances as Alyftrek, changes in behaviour and sleep disorders have been reported. Contact your doctor immediately if you (or someone taking this medicine) experiences any of the following symptoms, which may be signs of depression or other psychiatric disorders: sad or changed mood, anxiety, feelings of emotional discomfort, or thoughts of self-harm or suicide, difficulty sleeping and/or abnormal behaviour (see section 4).
• Consult your doctor if you have kidney problems or have had them in the past.
• If you have two Class I mutations (mutations known not to produce the CFTR protein), you should not take Alyftrek, as it is not expected that you will respond to this medicine.
• Contact your doctor if you have received an organ transplant, before starting treatment with Alyftrek.
• Contact your doctor if you previously took another medicine containing tezacaftor or ivacaftor and stopped it temporarily or permanently due to side effects. Your doctor may wish to monitor you more frequently.
• Contact your doctor if you are using a hormonal contraceptive (for birth control), for example, if you are a woman taking the oral contraceptive pill. During treatment with Alyftrek, you may have an increased risk of developing a skin rash. Contact your doctor if you develop a skin rash while taking Alyftrek.
• Your doctor may perform some eye examinations, before and during treatment with Alyftrek. In some children and adolescents receiving ivacaftor, which is similar to deutivacaftor, one of the active substances in Alyftrek, lens opacities (cataracts) have been observed, without any effect on vision.

Children under 6 years of age
Do not give this medicine to children under 6 years of age, as it is not known whether Alyftrek is safe
and effective in this age group.
Other medicines and Alyftrek
Inform your doctor or pharmacist if you are taking, have recently taken, or might take
any other medicines. Some medicines may affect how Alyftrek works or
increase the likelihood of side effects. In particular, inform your doctor if you are
taking any of the following medicines. Your doctor may need to adjust the dose of one of
these medicines if you are taking them.

• Antifungal medicines (used to treat fungal infections). These include fluconazole, itraconazole, ketoconazole, posaconazole and voriconazole.
• Antibiotic medicines (used to treat bacterial infections). These include clarithromycin, erythromycin, rifampicin, rifabutin and telithromycin.
• Anticonvulsant medicines (used to treat epileptic or seizure disorders). These include carbamazepine, phenobarbital and phenytoin.
• Herbal medicines. These include St John’s wort (Hypericum perforatum).
• Immunosuppressants (used after organ transplantation). These include ciclosporin, everolimus, sirolimus and tacrolimus.
• Cardiac glycosides (used to treat certain heart conditions). These include digoxin.
• Anticoagulant medicines (used to prevent blood clots). These include warfarin.
• Medicines for diabetes. These include glimepiride and glipizide.
• Medicines to lower blood pressure. These include verapamil.

Alyftrek with food and drink
During treatment, avoid foods or drinks containing grapefruit, as they may increase the
side effects of Alyftrek by increasing the amount of Alyftrek in the body.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding,
ask your doctor for advice before taking this medicine.

• Pregnancy: your doctor will help you decide what is best for you and your baby.
• Breastfeeding: tezacaftor has been detected in infants breastfed by mothers taking this medicine. There is insufficient information to determine whether vanzacaftor or deutivacaftor passes into breast milk; however, ivacaftor has been detected in infants breastfed by mothers taking this medicine. Your doctor will consider the benefits of breastfeeding for the infant and the benefits of treatment for you when helping you decide whether to discontinue breastfeeding or discontinue treatment.

Driving and using machines
Alyftrek may cause dizziness. If you feel dizzy, do not drive, ride a bicycle, or
use machinery, unless you are free of these symptoms.
Alyftrek contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e. essentially
‘sodium-free’.

3. How to take Alyftrek

Take this medicine exactly as directed by your doctor or pharmacist. If
you have any doubts, consult your doctor or pharmacist.
Alyftrek tablets are available in two different strengths. Your doctor will determine the correct dose for you.
Recommended dose in patients aged 6 years and older:

Take Alyftrek tablets with food containing fat. Meals or snacks containing fat are
those prepared with butter or oils, or those containing eggs. Other foods containing fat include:

• cheese, whole milk, whole milk-based dairy products, yoghurt, chocolate
• meat, fatty fish
• avocado, hummus, soy-based products (tofu)
• nuts, nutritional bars or nutritional drinks containing fat

While taking Alyftrek, avoid foods and drinks containing grapefruit. See Alyftrek with food and
drinks in section 2 for further details.
Swallow the tablets whole. Do not chew, crush, or split the tablets before
swallowing them.
Take them at approximately the same time each day. The tablets are for oral use.
You must continue taking all your other medicines unless your doctor tells you
otherwise.
If you have moderate liver problems, this medicine is not recommended, but your doctor will decide whether it is suitable for you to take this medicine.
If you have severe liver problems, you must not take this medicine. See also Warnings and
precautions in section 2.
If you take more Alyftrek than you should
Consult your doctor or pharmacist. If possible, bring the medicine and this leaflet
with you. You may experience adverse effects, including those listed in section 4 below.
If you forget to take Alyftrek
If you forget a dose, calculate how much time has passed since the time you should have taken the
dose.

• If less than 6 hours have passed since you should have taken the dose, take the missed tablets as soon as possible. Then return to your usual dosing schedule.
• If more than 6 hours have passed since you should have taken the dose, skip the missed dose and continue with your 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 advise you on how long you need to continue treatment with Alyftrek. It is
important to take this medicine regularly. Do not make any changes unless instructed by your
doctor.
If you have any doubts about how to use this medicine, consult 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 in people taking Alyftrek. These 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 urine

Depression. Signs include sad or changed mood, anxiety, feelings of emotional discomfort.
Contact your doctor immediately if you experience any of these symptoms.
Other side effects
Very common (may affect more than 1 in 10 people)

• Increased liver enzymes (signs of liver stress)
• Headache
• Diarrhoea
• Stomach ache (abdominal pain)
• Nasal congestion (blocked nose)
• Upper respiratory tract infection (nose and throat)
• Influenza
• Redness or sore throat (oropharyngeal pain)
• Dizziness
• Bacteria in sputum

Common (may affect up to 1 in 10 people)

• Depression
• Rash
• Increased creatine phosphokinase (a sign of muscle damage) observed in blood tests
• Anxiety
• Runny nose (rhinitis)
• Ear pain
• Ear discomfort
• Redness of the throat (pharyngeal erythema)
• Whistling or ringing in the ears (tinnitus)
• Increased blood flow to the eardrum, which may cause redness and inflammation (tympanic membrane hyperaemia)
• Inner ear nerve problems, which may affect hearing and balance (vestibular disorder)
• Sinus problems (sinus congestion)
• Nausea (feeling sick)
• Breast lumps (mammary mass)

Uncommon (may affect up to 1 in 100 people)

• Breast inflammation
• Blocked ear (aural congestion)
• Enlargement of the male breast (gynaecomastia)
• Nipple problems
• Nipple pain

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. 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 stated on the packaging after Scad./EXP. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents 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 calcium
vanzacaftor 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 calcium
vanzacaftor dihydrate equivalent to 10 mg of vanzacaftor.

The other components are:
• Tablet core: croscarmellose sodium (E468), hypromellose (E464), hypromellose acetate succinate, magnesium stearate (E470b), microcrystalline cellulose (E460(i)) and sodium lauryl sulfate (E487).
• Film coating: carmine (E120), brilliant blue FCF aluminium lake (E133), hydroxypropylcellulose (E463), hypromellose (E464), iron oxide red (E172), talc (E553b) and titanium dioxide (E171).
See the end of section 2 for important information on the contents of Alyftrek.

Description of the appearance of Alyftrek and pack contents
Alyftrek 50 mg/20 mg/4 mg film-coated tablets are round, purple tablets, with "V4" engraved on one side and smooth on the other.
Alyftrek 125 mg/50 mg/10 mg film-coated tablets are capsule-shaped, purple tablets, with "V10" engraved on one side and smooth 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 further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien България, Česká republika, Danmark, Deutschland, Eesti, España, 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

Ελλάδα
Vertex Φαρμακευτική Μονοπρόσωπη Ανώνυμη Εταιρία
Τηλ: +30 (211) 2120535

Italia
Vertex Pharmaceuticals (Italy) S.r.l.
Tel: +39 0697794000

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu/. In addition, links to other websites on rare diseases and their therapeutic treatments are provided.