Symkevi 50 mg/75 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Symkevi 50 mg/75 mg film-coated tablets

Symkevi 100 mg/150 mg film-coated tablets

tezacaftor/ivacaftor

Read the entire leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as 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, and you should not give it to others, even if they have the same symptoms as you, because it could harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Symkevi is and what it is used for

Symkevi contains two active substances, tezacaftor and ivacaftor. This medicine helps lung cells function better in certain patients with cystic fibrosis (CF). CF is an inherited condition in which the lungs and digestive system can become blocked with thick, sticky mucus.

Symkevi acts on a protein called CFTR (cystic fibrosis transmembrane conductance regulator), which is defective in some people with CF (those who have a mutation in the CFTR gene). Ivacaftor improves the function of the protein, while tezacaftor increases the amount of protein at the cell surface. Symkevi is usually taken with ivacaftor, another medicine.

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

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

2. What you need to know before taking Symkevi

Do not take Symkevi:

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

Consult your doctor before taking the tablets if any of the following apply to you.

Warnings and precautions

Consult your doctor if you have or have previously had liver problems. Your doctor may need to adjust your dose (see section 4).

• Your doctor will perform some blood tests to monitor your liver function before and during treatment with Symkevi, especially if previous blood tests showed elevated liver enzymes. Increased liver enzymes in the blood have been observed in patients with CF receiving Symkevi.

• Liver damage and worsening of liver function have been observed in patients with or without pre-existing liver disease who received other CFTR modulator regimens. Worsening liver function may be severe and could require liver transplantation.

Contact your doctor immediately if you experience any symptoms indicating liver problems. These are listed in section 4.

• Depression (including suicidal thoughts, changes in behavior, anxiety, and sleep disorders) has been reported in patients taking Symkevi, typically occurring within the first three months of treatment. Contact your doctor immediately if you (or someone taking this medicine) experience any of the following symptoms, which may be signs of depression: sad or altered mood, anxiety, emotional discomfort, thoughts of self-harm or suicide, and/or difficulty sleeping (see section 4).

• Your doctor may perform eye examinations before and during treatment with Symkevi. In some children and adolescents receiving this treatment, lens opacities (cataracts) have occurred without affecting vision.

• Consult your doctor if you have or have previously had kidney problems.

• Consult your doctor before starting treatment if you have undergone organ transplantation.

Children under 6 years of age

Symkevi must not be used in children under 6 years of age. It is unknown whether Symkevi is safe and effective in children under 6 years of age.

Other medicines and Symkevi

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines. Some medicines may affect how Symkevi works or may increase the likelihood of side effects. In particular, consult your doctor if you are taking any of the following medicines. Your doctor may adjust the dose of one of the medicines if you are taking any 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). These include phenobarbital, carbamazepine, and phenytoin.
• Herbal medicines. These include St. John’s wort (Hypericum perforatum).
• Immunosuppressants (used after organ transplantation). These include cyclosporine, tacrolimus, sirolimus, and everolimus.
• Cardiac glycosides (used to treat certain heart conditions). These include digoxin.
• Anticoagulants (used to prevent blood clots). These include warfarin.
• Medicines for diabetes. These include glimepiride and glipizide.

Taking Symkevi with food and drink

Avoid grapefruit-containing foods or beverages 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, think you may be pregnant, or are planning to become pregnant, consult your doctor before using this medicine.

• Pregnancy: It may be preferable to avoid using this medicine during pregnancy. Your doctor will help you decide what is best for you and your baby.
• Breastfeeding: Tezacaftor and ivacaftor may be excreted in breast milk. Your doctor will consider the benefit of breastfeeding for the child and the benefit of treatment for you to help you decide whether to discontinue breastfeeding or discontinue treatment.

Driving and using machines

Symkevi may cause dizziness. If you feel dizzy, do not drive, ride a bicycle, or use machinery unless you are certain it does not affect you.

Symkevi contains sodium

This medicine contains less than 23 mg of sodium (1 mmol) per dose unit; essentially “sodium-free”.

3. How to take Symkevi

Follow exactly the instructions for administration of this medicine given by your doctor.

If in doubt, consult your doctor or pharmacist again.

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

Symkevi is usually taken with ivacaftor.

Take the tablets at approximately 12-hour intervals.

Take Symkevi tablets and ivacaftor tablets with food containing fat. Meals or snacks containing fat include those prepared with butter or oils, or those containing eggs. Examples of other foods containing fat are:

• Cheese, whole milk, whole milk dairy products, yoghurt, chocolate
• Meats, fatty fish
• Avocado, hummus (chickpea purée), soy-based products (tofu)
• Nuts, nutritional bars or drinks containing fat

The tablets are taken orally.

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

You must continue taking all other medications unless your doctor tells you to stop.

If you have liver problems, either moderate or severe, your doctor may need to reduce your dose of tablets, as your liver will not process this medicine as quickly as usual.

If you take more Symkevi than you should

Contact 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 Symkevi

• If you forget to take your morning dose of Symkevi or your evening dose of ivacaftor, and you remember within 6 hours of the scheduled time, take the missed tablet immediately.
• If more than 6 hours have passed, do not take the missed tablet. Wait and take the next tablet at the usual time.
• Do not take two tablets to make up for a missed dose.

If you stop taking Symkevi

Your doctor will advise you how long you need to take Symkevi. It is important to take this medicine consistently. Do not make any changes unless your doctor tells you to.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Serious adverse effects

Possible signs of liver problems

Increased liver enzymes in the blood are very common in patients with CF. This may be a sign of liver problems:

• Pain or discomfort in the upper right part of the stomach (abdominal area)
• Yellowing of the skin or whites of the eyes
• Loss of appetite
• Nausea or vomiting
• Dark-colored urine

Depression

Signs of depression include a sad or depressed mood, anxiety, or a feeling of emotional distress.

Contact your doctor immediately if you experience any of these symptoms.

Adverse 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
• Nasal congestion (sinus congestion)
• Dizziness

Adverse effects observed with ivacaftor:

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

• Infection of the upper respiratory tract (common cold), including sore throat and nasal congestion
• Headache
• Dizziness
• Stomach (abdominal) pain
• Diarrhea
• Increased liver enzymes in the blood
• Rash
• Changes in the type of bacteria present in mucus

Common (may affect up to 1 in 10 people)

• Runny nose
• Ear pain, ear discomfort
• Ringing in the ears
• Redness inside the ears
• Inner ear disorder (sensation of dizziness or spinning)
• Sinus congestion
• Redness of the throat
• Breast lump

Uncommon (may affect up to 1 in 100 people)

• Blocked ears
• Breast inflammation
• Breast enlargement in males
• Changes or pain in the nipples

Additional adverse effects in children and adolescents

Adverse effects observed in children and adolescents are similar to those observed in adults.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Symkevi

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 CAD/EXP. The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage conditions.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of any unused medicine and its packaging. This will help protect the environment.

6. Contents of the pack and other information

The active substances are tezacaftor and ivacaftor.

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

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

The other components are:

• Tablet core: hypromellose acetate succinate, 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 tezacaftor/150 mg ivacaftor film-coated tablets

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

The other components are:

• Tablet core: hypromellose acetate succinate, 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 pack

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

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

Symkevi is available in the following pack sizes:

Pack size of 28 tablets (4 blister cards of 7 tablets each).

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
County Armagh
BT63 5UA
United Kingdom

Date of latest revision of this leaflet:

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu. Links to other websites on rare diseases and orphan medicines are also provided.