STAYVEER 125mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

STAYVEER 125 mg film-coated tablets

bosentan

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.

Contents of the pack

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

1. What is STAYVEER and what is it used for

STAYVEER tablets contain bosentan, which blocks a natural hormone called endothelin-1 (ET-1), causing narrowing of blood vessels. STAYVEER therefore causes widening of the blood vessels and belongs to a class of medicines called “endothelin receptor antagonists”.

STAYVEER is used to treat:

• Pulmonary arterial hypertension(PAH): PAH is a disease of severe narrowing of the blood vessels in the lungs, leading to an increase in blood pressure in the blood vessels (pulmonary arteries) that carry blood from the heart to the lungs. This pressure reduces the amount of oxygen that can reach the blood in the lungs, making physical activity more difficult. STAYVEER widens the pulmonary arteries, making it easier for the heart to pump blood through them. This reduces blood pressure and alleviates symptoms.

STAYVEER is used for the treatment of patients with PAH in functional class III to improve symptoms and exercise capacity (the ability to perform physical activity). The “class” reflects the severity of the disease: ‘class III’ implies marked limitation of physical activity. Some improvements have been observed in patients with PAH class II. The ‘class II’ implies slight limitation of physical activity. The PAH for which STAYVEER is indicated may be:

• primary (in which no cause is identified or hereditary);
• caused by scleroderma (also called systemic sclerosis, a disease in which there is abnormal growth of connective tissue that forms the support of the skin and other organs);
• caused by congenital heart defects (present at birth) with shunts (abnormal communications) that cause abnormal blood flow between the heart and lungs.

• Digital ulcers(ulcers on the fingers and toes) in adult patients suffering from a disease called scleroderma. STAYVEER reduces the number of new digital ulcers (on hands and feet) that appear.

2. What you need to know before you take STAYVEER

Do not take STAYVEER:

• if you are allergic to bosentanor any of the other ingredients of this medicine (listed in section 6)
• if you have liver problems(ask your doctor)
• if you are pregnant, or could be pregnantbecause you are not using reliable contraceptives. Please read the information in the section “Contraceptives” and “Other medicines and STAYVEER”
• if you are taking ciclosporin A(a medicine used after transplants or to treat psoriasis)

If you have any of these conditions, inform your doctor.

Warnings and precautions

Tests that your doctor will perform before prescribing treatment

• a blood test to assess liver function
• a blood test to detect if you have anemia (low hemoglobin)
• a pregnancy test if you are a woman of childbearing age

Abnormalities in liver function tests and anemia have been found in some patients taking STAYVEER.

Blood tests that your doctor will perform during treatment

During treatment with STAYVEER, your doctor will schedule regular blood tests to monitor changes in your liver function and hemoglobin levels.

For all these tests, please refer to the Patient Alert Card (inside the box of STAYVEER tablets). It is essential that you have regular blood tests while taking STAYVEER. We suggest that you write the date of the most recent test and also your next test (ask your doctor for the date) on the Patient Alert Card to help you remember when you have your next visit.

Liver function tests

These tests must be performed monthly throughout the duration of treatment with STAYVEER. After a dose increase, an additional test must be performed after 2 weeks.

Anemia tests

These tests will be performed monthly during the first 4 months of treatment and then every 3 months, as patients taking STAYVEER may develop anemia.

If these tests are abnormal, your doctor may decide to reduce the dose or interrupt treatment with STAYVEER and perform additional tests to investigate the cause.

Children and adolescents

STAYVEER is not recommended in pediatric patients with systemic sclerosis with active digital ulcers. See also section 3. How to take STAYVEER.

Taking STAYVEER with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines, including those obtained without a prescription. It is especially important that you inform your doctor if you are taking:

• ciclosporin A (a medicine used after transplants or to treat psoriasis) that must not be taken with STAYVEER.
• sirolimus or tacrolimus, which are medicines used after transplants, and are not recommended to be taken with STAYVEER.

• glibenclamide (a medicine for diabetes), rifampicin (a medicine for tuberculosis), fluconazole (an antifungal medicine), ketoconazole (a medicine used to treat Cushing's syndrome), or nevirapine (a medicine for HIV) as these medicines are not recommended to be taken with STAYVEER.
• other medicines for the treatment of HIV infection, which when taken with STAYVEER may require special monitoring.
• oral contraceptives, which are not effective as the only contraceptive method when taking STAYVEER. Inside the box of STAYVEER tablets, you will find a Patient Alert Card that you must read carefully. Your doctor and/or gynecologist will determine the appropriate contraceptive method for you.
• other medicines for the treatment of pulmonary hypertension: sildenafil and tadalafil;
• warfarin (an anticoagulant);
• simvastatin (used to treat high cholesterol).

Driving and using machines

STAYVEER has no influence or negligible influence on the ability to drive and use machines. However, STAYVEER may cause hypotension (low blood pressure) that can cause dizziness, affect your vision, and affect your ability to drive and use machines. Therefore, if you feel dizzy or have blurred vision while taking STAYVEER, do not drive or operate tools or machinery.

Women of childbearing age

Do not take STAYVEER if you are pregnant or planning to become pregnant

Pregnancy tests

STAYVEER may affect unborn children conceived before or during treatment. If you are a woman of childbearing age, your doctor will ask you to have a pregnancy test before starting treatment with STAYVEER and regularly while taking STAYVEER.

Contraceptives

If you may become pregnant, use a reliable contraceptive method (contraception) while taking STAYVEER. Your doctor or gynecologist will advise you on reliable contraceptive methods while taking STAYVEER. Since STAYVEER can make hormonal contraception ineffective (e.g., oral, injection, implant, or patches), this method alone is not reliable. Therefore, if you use hormonal contraceptives, you must also use a barrier method (e.g., female condom, diaphragm, contraceptive sponge, or your partner must also use a condom). Inside the box of STAYVEER tablets, you will find a Patient Alert Card. You must complete this card and bring it to your doctor at your next visit so that your doctor or gynecologist can determine if you need an alternative or additional reliable contraceptive method. It is recommended to have a monthly pregnancy test while taking STAYVEER and being of childbearing age.

Tell your doctor immediately if you become pregnant while taking STAYVEER or plan to become pregnant in the near future.

Breast-feeding

Tell your doctorimmediately if you are breast-feeding. You are advised to stop breast-feeding if you are prescribed STAYVEER, as it is not known whether this medicine passes into breast milk.

Fertility

If you are a man taking STAYVEER, this medicine may decrease your sperm count. It cannot be excluded that it may affect your ability to father a child. Talk to your doctor if you have any questions or concerns about this.

3. How to take STAYVEER

Treatment with STAYVEER should only be started and controlled by a doctor who has experience in the treatment of PAH or systemic sclerosis. Follow exactly the instructions for administration of this medicine given by your doctor. If you are unsure, consult your doctor or pharmacist again.

STAYVEER with food and drink

STAYVEER can be taken with or without food.

The recommended dose is:

Adult

Treatment in adults usually starts with 62.5 mg twice a day (morning and evening) for the first 4 weeks, then your doctor will normally advise you to take one 125 mg tablet twice a day, depending on how you react to STAYVEER.

Children and adolescents

The recommended dose in children is only for PAH. For children from 1 year of age, treatment with STAYVEER usually starts with 2 mg per kg of body weight twice a day (morning and evening). Your doctor will advise you on the dose.

If you think that the effect of STAYVEER is too strong or too weak, talk to your doctor to check if you need a dose adjustment.

How to take STAYVEER

The tablets should be taken (morning and evening) with water. The tablets can be taken with or without food.

If you take more STAYVEER than you should

If you take more tablets than you should, talk to your doctor immediately.

If you forget to take STAYVEER

If you forget to take STAYVEER, take the dose as soon as you remember and then continue taking it at your usual time. Do not take a double dose to make up for forgotten doses.

If you stop taking STAYVEER

If you suddenly stop taking STAYVEER, your symptoms may worsen. Do not stop taking STAYVEER unless your doctor tells you to. Your doctor may advise you to reduce the dose for a few days before stopping it completely.

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.

The most serious side effects with STAYVEER are:

• Abnormal liver function that may affect more than 1 in 10 people
• Anemia (low blood count) that may affect more than 1 in 10 people. Anemia may occasionally require blood transfusion.

Your liver and blood values will be checked during treatment with STAYVEER (see section 2). It is essential that you have these checks as prescribed by your doctor.

Signs that your liver may not be working properly include:

• nausea (feeling sick)
• vomiting
• fever (high temperature)
• stomach pain (abdominal pain)
• jaundice (yellowing of the skin or whites of the eyes)
• dark-colored urine
• itching of the skin
• lethargy or fatigue (unusual tiredness or exhaustion)
• flu-like syndrome (joint and muscle pain with fever)

If you have any of these symptoms, talk to your doctor immediately

Other side effects:

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

• headache
• edema (swelling of the legs and ankles or other signs of fluid retention)

Common(may affect up to 1 in 10people):

• flushing (redness of the skin)
• hypersensitivity reactions (including skin inflammation, itching, and skin rash)
• gastroesophageal reflux (acid reflux)
• diarrhea
• fainting (fainting)
• palpitations (rapid or irregular heartbeats)
• low blood pressure
• nasal congestion

Uncommon(may affect up to 1 in 100people):

• thrombocytopenia (low platelet count)
• neutropenia/leucopenia (low white blood cell count)
• elevated liver function tests with hepatitis (inflammation of the liver) including possible exacerbation of hepatitis and/or jaundice (yellowing of the skin or whites of the eyes)

Rare(may affect up to 1 in 1000people):

• anaphylaxis (severe allergic reaction), angioedema (swelling, most frequently around the eyes, lips, tongue, or throat)
• liver cirrhosis (scarring), liver failure (severe liver dysfunction)

Blurred vision has also been reported with an unknown frequency (cannot be estimated from the available data).

Side effects in children and adolescents

The side effects that have been observed in children treated with STAYVEER are the same as in adults.

Reporting of side effects:

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storing STAYVEER

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 carton and on the blister after “EXP”.

For the high-density polyethylene white bottles, use within 30 days of first opening.

For the PVC/PE/PVDC/aluminum blisters:

Do not store above 30 °C.

For the high-density polyethylene white bottles:

No special storage conditions are required.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Package Contents and Additional Information

Composition of STAYVEER

• STAYVEER 125 mg film-coated tablets:The active ingredient is bosentan monohydrate. Each tablet contains 125 mg of bosentan (as monohydrate).
• The other ingredientsof the tablet core are corn starch, pregelatinized starch, sodium carboxymethyl starch (Type A), povidone, glycerol dibehenate, and magnesium stearate. The film coatingcontains hypromellose, glycerol triacetate, talc, titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172), and ethylcellulose.

Appearance of the Product and Package Contents

STAYVEER 125 mg are oval, orange-white, film-coated tablets engraved with «125» on one side.

PVC/PE/PVDC/Aluminum blisterscontaining 14 film-coated tablets. The packages contain 56 or 112 film-coated tablets (STAYVEER 125 mg film-coated tablets).

High-density polyethylene (HDPE) white bottles with a silica gel desiccantcontaining 56 film-coated tablets. Cardboard box containing 56 film-coated tablets (STAYVEER 125 mg film-coated tablets).

Do not swallow the desiccant.

Only some pack sizes may be marketed.

Marketing Authorization Holder:

Janssen-Cilag International NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

Manufacturer

Haupt Pharma Wülfing GmbH

Bethelner Landstraße 18

31028 Gronau/Leine

Germany

Date of Last Revision of this Leaflet:

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu/