Product Information for the Patient

Symkevi 50 mg/75 mg Film-Coated Tablets

Symkevi 100 mg/150 mg Film-Coated Tablets

tezacaftor/ivacaftor

Read this entire product information carefully before starting to take this medicine, as it contains important information for you.

• Keep this product information, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this product information. See section 4.

Symkevi contains two active ingredients,tezacaftor and ivacaftor. 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 blocked with thick and sticky mucus.

Symkevi acts on a protein called CFTR (cystic fibrosis transmembrane conductance regulator), which is damaged in some people with CF (who have a mutation in the CFTR gene). Ivacaftor makes the protein work better while tezacaftor increases the amount of protein on the cell surface. Symkevi is usually taken with ivacaftor, another medication.

Symkevi taken with ivacaftor is for the long-term treatment of patients aged 6 years or older who suffer from CF with certain genetic mutations that result in a decrease in the amount and/or function of the CFTR protein.

Symkevi taken with ivacaftor helps your breathing by improving your lung function. You may notice that you do not get sick as often and/or that it is easier for you to gain weight.

Do not take Symkevi:

• if you are allergic to tezacaftor, ivacaftor, or any of the other ingredients of this medication (listed in section 6).

Consult your doctor,without taking the tablets, if this is the case.

Warnings and precautions

• Consult your doctor if you have liver problems or have had them in the past. Your doctor may need to adjust your dose.

• Your doctor will perform some blood tests to check how your liver is before and during treatment with Symkevi, especially if previous blood tests showed elevated liver enzymes. An increase in liver enzymes in the blood has been observed in patients with CF who receive Symkevi.

• Severe liver damage and worsening of liver function have been observed in patients with severe liver disease who received other CFTR modulators. Worsening of liver function can be severe and may require a transplant.

Inform your doctor immediatelyif you have any symptoms indicative of liver problems. These are listed in section 4.

• Depression (including suicidal thoughts and behaviors) has been reported in patients taking Symkevi, usually appearing in the first three months of treatment. Consult your doctor immediately if you (or someone taking this medication) experience any of the following symptoms, which may be signs of depression: sad or altered mood, anxiety, emotional discomfort, or thoughts of self-harm or suicide.

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

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

• Consult your doctorbefore starting treatment if you have received an organ transplant.

Children under 6 years

Symkevi should not be used in children under 6 years. The safety and efficacy of Symkevi in children under 6 years are unknown.

Other medications and Symkevi

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 Symkevi 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 ketoconazole, itraconazole, posaconazole, voriconazole, and fluconazole.
• Antibiotics(used to treat bacterial infections). These include telithromycin, clarithromycin, erythromycin, rifampicin, and rifabutin.
• Anticonvulsants(used to treat epilepsy and seizures or convulsions). These include phenobarbital, carbamazepine, and phenytoin.
• Herbal medicines.These include St. John's Wort (Hypericum perforatum).
• Immunosuppressants(used after an organ transplant). These include cyclosporin, tacrolimus, sirolimus, and everolimus.
• 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 and glipizide.

Taking Symkevi with food and drinks

Avoid foods or drinks containing grapefruit during treatment as they may increase the adverse effects of Symkevi by increasing the amount of Symkevi in the blood.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, or plan to become pregnant, consult your doctor before using this medication.

• Pregnancy: it may be better to avoid using this medication during pregnancy. Your doctor will help you decide what is best for you and your child.
• Breastfeeding:tezacaftor and ivacaftor may be excreted in breast milk. Your doctor will consider the benefits of breastfeeding for the baby and the benefits of treatment for you to help you decide whether to stop breastfeeding or stop treatment.

Driving and operating machinery

Symkevi may cause dizziness. If you feel dizzy, do not drive, ride a bike, or use machines unless you are sure it will not affect you.

Symkevi contains sodium

This medication contains less than 23 mg of sodium (1 mmol) per dose; it is essentially "sodium-free".

Follow exactly the administration instructions of this medication indicated by your doctor.

In case of doubt, consult your doctor or pharmacist again.

There are different doses of Symkevy for different age groups. Check that you have been prescribed the correct dose (below).

Symkevi is usually taken with ivacaftor.

Take the tablets with an interval of about 12 hours.

Take the tablets ofSymkevi and ivacaftor with foods that contain fats.Foods 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

The tablets are taken orally.

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 need to reduce your dose of tablets, as your liver will not process this medication as quickly as usual.

If you take more Symkevi than you should

Consult your doctor or pharmacist.If possible, bring the medication and this leaflet. You maypresent adverse effects, including those mentioned in section 4 below.

If you forgot to take Symkevi

• If you forget to take the morning dose of Symkevy or the evening tablet of ivacaftor, and you rememberwithin 6 hoursfrom the scheduled time when you were supposed to take the dose, take the missed tablet immediately.
• If more than6 hourshave passed, do not take the missed tablet. Wait and take the next tablet at the usual time.
• Do nottake 2 tablets to make up for the missed dose.

If you interrupt treatment with Symkevi

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

If you have any other doubts 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

The increase in liver enzymes in the blood is very common in patients with FQ. This can be a sign of liver problems:

• Upper right abdominal pain or discomfort
• Yellowing of the skin or the white part of the eyes
• Loss of appetite
• Nausea or vomiting
• Dark-colored urine

Depression

The signs of depression include a sad or altered mood, anxiety, or emotional discomfort.

Inform your doctor immediatelyif you experience any of these symptoms.

Side effects observed with Symkevi:

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

• Headache
• Common cold

Common(may affect up to 1 in 10 people)

• Nausea
• Stuffy nose (nasal congestion)
• Dizziness

Side effects observed with ivacaftor:

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

• Upper respiratory tract infection (common cold), including sore throat andnasal congestion
• Headache
• Dizziness
• Abdominal pain
• Diarrhea
• Increased liver enzymes in the blood
• Rash
• Changes in the type of bacteria in mucus

Common(may affect up to 1 in 10 people)

• Runny nose
• Ear pain, ear discomfort
• Tinnitus
• Redness in the ear canal
• Vestibular disorder (feeling of dizziness or spinning)
• Nasal congestion
• Redness of the throat
• Breast lump

Rare(may affect up to 1 in 100 people)

• Ear blockage
• Mastitis
• Enlargement of the breasts in men
• Changes or pain in the nipples

Additional side effects in children and adolescents

The side effects observed in children and 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 prospectus. 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 about 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 packaging after CAD/EXP. 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.

The active ingredients are tezacaftor and ivacaftor.

Symkevi 50 mg of tezacaftor/75 mg of ivacaftor film-coated tablets

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

The other components are:

• Tablet core: acetate succinate of hypromellose, sodium lauryl sulfate (E487), hypromellose 2910 (E464), microcrystalline cellulose (E460(i)), sodium croscarmellose (E468), and magnesium stearate (E470b) (see section 2 “Symkevi contains sodium”).
• Tablet coating: hypromellose 2910 (E464), hydroxypropyl cellulose (E463), titanium dioxide (E171), and talc (E553b).

Symkevi 100 mg of tezacaftor/150 mg of ivacaftor film-coated tablets

Each film-coated tablet contains 100 mg of tezacaftor and 150 mg of ivacaftor.

The other components are:

• Tablet core: acetate succinate of hypromellose, sodium lauryl sulfate (E487), hypromellose 2910 (E464), microcrystalline cellulose (E460(i)), sodium croscarmellose (E468), and magnesium stearate (E470b) (see section 2 “Symkevi contains sodium”).
• Tablet coating: hypromellose 2910 (E464), hydroxypropyl cellulose (E463), titanium dioxide (E171), talc (E553b), and yellow iron oxide (E172).

Appearance of the product and contents of the package

Symkevi 50 mg/75 mg film-coated tablets are oblong tablets (12.70 mm x 6.78 mm) of white color with the imprint “V50” on one side and smooth on the other.

Symkevi 100 mg /150 mg film-coated tablets are oblong tablets (15.9 mm x 8.5 mm) of yellow color with the imprint “V100” on one side and smooth on the other.

Symkevi is available in the following package sizes:

Package size of 28 tablets (4 blister cards of 7 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 for manufacturing

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

UK

Last revision date of this leaflet:

Other sources of information

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