Stayveer 125 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

STAYVEER 125 mg film-coated tablets

bosentan

Read the entire 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 and must not be given to other people, even if they have the same symptoms as yours, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet.

Contents of the leaflet

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

1. What STAYVEER is and what it is used for

STAYVEER tablets contain bosentan, which blocks a naturally occurring hormone called endothelin-1 (ET-1) that causes narrowing of blood vessels. STAYVEER therefore causes dilation of blood vessels and belongs to a class of medicines known as “endothelin receptor antagonists”.

STAYVEER is used to treat:

• Pulmonary arterial hypertension (PAH): PAH is a disease characterized by severe narrowing of the blood vessels in the lungs, leading to increased 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 enter 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 PAH patients in class III to improve symptoms and exercise capacity (the ability to perform physical activity). The “class” reflects the severity of the disease: ‘class III’ means marked limitation of physical activity. Some improvements have been observed in PAH patients in class II. ‘Class II’ means slight limitation of physical activity. The PAH for which STAYVEER is indicated may be:

• primary (where no cause is identified or is hereditary);

• caused by scleroderma (also called systemic sclerosis, a disease characterized by abnormal growth of connective tissue that supports the skin and other organs);

• caused by congenital heart defects (present at birth) with shunts (abnormal connections) causing 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 (in hands and feet) that develop.

2. What you need to know before starting to take STAYVEER

Do not take STAYVEER:

• if you are allergic to bosentan or any of the other components of this medicine (listed in section 6)
• if you have liver problems (ask your doctor)
• if you are pregnant, or could be pregnant due to not using reliable contraceptive methods. Please read the information in the sections “Contraceptives” and “Other medicines and STAYVEER”
• if you are taking cyclosporine A (a medicine used after transplantation or to treat psoriasis)

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

Warnings and precautions

Tests your doctor will perform before prescribing treatment

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

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

Blood tests 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 (included inside the STAYVEER tablet packaging). It is important that you undergo regular blood tests while taking STAYVEER. We recommend that you write the date of your most recent test and your next scheduled test (ask your doctor for the date) on the Patient Alert Card to help you remember when your next visit is due.

Blood tests for liver function

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

Blood tests for anemia

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

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

Children and adolescents

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

Taking STAYVEER with other medicines

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

• cyclosporine A (a medicine used after organ transplantation and for the treatment of psoriasis), which must not be taken together with STAYVEER.

• sirolimus or tacrolimus, which are medicines used after transplantation and are not recommended to be taken with STAYVEER.

• glibenclamide (a medicine for diabetes), rifampicin (a medicine for tuberculosis), fluconazole (a medicine for fungal infections), ketoconazole (a medicine used to treat Cushing's syndrome), or nevirapine (a medicine for HIV), as these are not recommended to be taken together 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 sole method of contraception when taking STAYVEER. Inside the STAYVEER packaging, 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 hypercholesterolemia).

Driving and use of machines

STAYVEER has no effect or its effect is negligible on the ability to drive and use machines. However, STAYVEER may cause hypotension (low blood pressure), which can lead to dizziness, blurred vision, and may impair your ability to drive or operate machinery. Therefore, if you feel dizzy or experience blurred vision while taking STAYVEER, do not drive or operate tools or machinery.

Women of childbearing potential

DO NOT take STAYVEER if you are pregnant or planning to become pregnant.

Pregnancy tests

STAYVEER may harm unborn children conceived before or during treatment. If you are a woman of childbearing potential, your doctor will require you to take a pregnancy test before starting treatment with STAYVEER and regularly while taking STAYVEER.

Contraception

If you could become pregnant, use a reliable method of contraception (contraception) while taking STAYVEER. Your doctor or gynecologist will advise you on reliable contraceptive methods while taking STAYVEER. Since STAYVEER may reduce the effectiveness of hormonal contraception (e.g., oral, injection, implant, or transdermal patches), this method alone is not reliable. Therefore, if you use hormonal contraception, you must also use a barrier method (e.g., female condom, diaphragm, contraceptive sponge, or your partner should use a male condom). Inside the STAYVEER tablet packaging, you will find the 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 whether you need an alternative or additional reliable contraceptive method. A monthly pregnancy test is recommended while you are taking STAYVEER and are of childbearing age.

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

Breastfeeding

Inform your doctor immediately if you are breastfeeding. You are advised to discontinue breastfeeding if you are prescribed STAYVEER, as it is unknown whether this medicine passes into breast milk.

Fertility

If you are a man taking STAYVEER, this medicine may reduce your sperm count. A potential impact on fertility cannot be ruled out. Talk to your doctor if you have any questions or concerns about this.

3. How to take STAYVEER

Treatment with STAYVEER should only be initiated and monitored by a physician experienced in the treatment of pulmonary arterial hypertension (PAH) or systemic sclerosis. Always follow your doctor's instructions for administering this medicine exactly. If you are unsure, consult your doctor or pharmacist again.

STAYVEER with food and drink

STAYVEER may be taken with or without food.

Recommended dose:

Adults

Treatment in adults usually starts with 62.5 mg twice daily (morning and evening) for the first 4 weeks. After this, your doctor will usually advise you to increase to one 125 mg tablet twice daily, depending on your response to STAYVEER.

Children and adolescents

The recommended dose in children is indicated only for PAH. For children aged 1 year and older, treatment with STAYVEER usually starts at 2 mg per kg of body weight twice daily (morning and evening). Your doctor will advise you on the appropriate dose.

If you feel that the effect of STAYVEER is too strong or too weak, consult your doctor to determine whether a dose adjustment is needed.

How to take STAYVEER

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

If you take more STAYVEER than you should

If you take more tablets than prescribed, contact your doctor immediately.

If you forget to take STAYVEER

If you forget to take a dose of STAYVEER, take it as soon as you remember, and then continue taking it according to your usual schedule. Do not take a double dose to make up for a missed dose.

If you stop taking STAYVEER

If you suddenly stop treatment with STAYVEER, your symptoms may worsen. Do not discontinue STAYVEER unless instructed by your doctor. Your doctor may advise you to gradually reduce the dose over several days before stopping completely.

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 produce adverse effects, although not everyone experiences them.

The most serious adverse effects with STAYVEER are:

• Abnormal liver function, which may affect more than 1 in 10 people
• Anaemia (reduced blood count), which may affect more than 1 in 10 people. Anaemia may occasionally require blood transfusion.

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

Signs that your liver may not be functioning properly include:

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

If you experience any of these symptoms, consult your doctor immediately.

Other adverse effects:

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

• Headache
• Oedema (swelling of legs and ankles or other signs of fluid retention)

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

• Flushing (redness of the skin)
• Hypersensitivity reactions (including skin inflammation, itching, and skin rash)
• Gastro-oesophageal reflux (acid reflux)
• Diarrhoea
• Syncope (fainting)
• Palpitations (rapid or irregular heartbeat)
• Low blood pressure
• Nasal congestion

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

• Thrombocytopenia (decreased number of platelets in the blood)
• Neutropenia/leucopenia (decreased number of white blood cells in the blood)
• Elevated liver function tests with hepatitis (liver inflammation), including possible exacerbation of hepatitis and/or jaundice (yellowing of the skin or whites of the eyes)

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

• Anaphylaxis (generalised allergic reaction), angioedema (swelling, more frequently around the eyes, lips, tongue or throat)
• Liver cirrhosis (fibrosis), liver failure (severe impairment of liver function)

Cases of blurred vision have also been reported with unknown frequency (frequency cannot be estimated from the available data).

Adverse effects in children and adolescents

The adverse effects observed in children treated with STAYVEER are the same as those in adults.

Reporting of adverse effects:

If you experience any type of adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You may 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 STAYVEER

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the carton and on the blister after “EXP”.

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

For PVC/PE/PVDC/aluminum blisters:

Do not store above 30 °C.

For white high-density polyethylene bottles:

No special storage conditions required.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging once they are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

Composition of STAYVEER

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

Appearance of the product and contents of the pack

STAYVEER 125 mg are film-coated, orange-white, oval tablets marked with "125" on one side.

PVC/PE/PVDC/aluminum blisters containing 14 film-coated tablets. The packs contain 56 or 112 film-coated tablets (STAYVEER 125 mg film-coated tablets).

White high-density polyethylene (HDPE) bottles with a silica gel desiccant containing 56 film-coated tablets. Carton pack 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 the most recent review of this leaflet:

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