BOSENTAN SUN 62.5 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Bosentan SUN 62.5 mg film-coated tablets EFG

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

1. What is Bosentan SUN and what is it used for

The tablets of Bosentan SUN contain bosentan, which blocks a natural hormone called endothelin-1 (ET-1), causing narrowing of blood vessels. Bosentan causes, consequently, dilation of blood vessels and belongs to a class of medicines called "endothelin receptor antagonists".

Bosentan SUN 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 decreases the amount of oxygen that can reach the blood in the lungs, making physical activity more difficult. Bosentan widens the pulmonary arteries, making it easier for the heart to pump blood through them. This reduces blood pressure and alleviates symptoms.

Bosentan SUN is used for the treatment of patients with PAH 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 Bosentan SUN 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.

(comprising abnormal communications that cause abnormal blood flow between the heart and lungs).

• Digital ulcers (ulcers on the fingers of the hands and feet) in adult patients who

suffer from a disease called scleroderma. Bosentan SUN reduces the number of new digital ulcers (on hands and feet) that appear.

2. What you need to know before you take Bosentan SUN

Do not take Bosentan SUN:

• if you are allergic to bosentan or 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 pregnant by not using reliable contraceptive methods. Please read the information in the section "Contraceptives" and "Other medicines and Bosentan SUN"
• if you are taking ciclosporin A (a medicine used after transplantation or to treat psoriasis)

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

Warnings and precautions

Consult your doctor or pharmacist before starting treatment with Bosentan SUN.

Tests that your doctor will perform before starting 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 Bosentan (low hemoglobin)

Blood tests that your doctor will perform during treatment

During treatment with Bosentan SUN, 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 Bosentan SUN tablets). It is essential that you have regular blood tests while taking Bosentan SUN. 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 Bosentan SUN. 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 Bosentan SUN may develop anemia.

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

Children and adolescents

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

Taking Bosentan SUN 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 medicine used after transplants and to treat psoriasis) that must not be administered with Bosentan SUN.
• sirolimus or tacrolimus, which are medicines used after transplants, and are not recommended to be administered with Bosentan SUN.

• glibenclamide (a medicine for diabetes), rifampicin (a medicine for tuberculosis), or fluconazole (an antifungal medicine), ketoconazole (a medicine used to treat Cushing's syndrome), or nevirapine (a medicine for HIV), as it is not recommended to administer these medicines with Bosentan SUN.

• other medicines for the treatment of HIV infection, which, when administered with Bosentan SUN, may require special monitoring.
• oral contraceptives, which are not effective as the only contraceptive method when taking Bosentan SUN. Inside the box of Bosentan SUN, 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).

Pregnancy, breastfeeding, and fertility

Women of childbearing age

DO NOT take Bosentan SUN if you are pregnant or plan to become pregnant.

Pregnancy tests

Bosentan SUN 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 bosentan and regularly while taking bosentan.

Contraceptives

If you may become pregnant, use a reliable contraceptive method (contraception) while taking Bosentan SUN. Your doctor or gynecologist will advise you on reliable contraceptive methods while taking Bosentan SUN. Since Bosentan SUN 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 Bosentan SUN, 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 if you need an alternative or additional reliable contraceptive method. It is recommended to have a monthly pregnancy test while taking Bosentan SUN and being of childbearing age.

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

Breastfeeding

Bosentan passes into breast milk. You are advised to interrupt breastfeeding if you are prescribed Bosentan SUN, as it is not known whether this medicine can harm your baby. Inform your doctor about this.

Fertility

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

Driving and using machines

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

Bosentan SUN contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per tablet; this is, essentially "sodium-free".

3. How to take Bosentan SUN

Treatment with Bosentan SUN should only be initiated and controlled by a doctor who has experience in the treatment of PAH or systemic sclerosis. Follow exactly the administration instructions of this medicine indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

Bosentan SUN with food and drink

Bosentan SUN can be administered 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, after which your doctor will normally advise you to take a 125 mg tablet twice a day, depending on how you react to Bosentan SUN.

Children and adolescents

The recommended dose in children is only for PAH. For children from 1 year of age, treatment with Bosentan SUN usually starts with 2 mg per kg of body weight twice a day (morning and evening); however, some doses of bosentan are not possible in children with a body weight below 31 kg. For these patients, a bosentan tablet with a lower dose is required. Your doctor will advise you on the dose.

If you feel that the effect of Bosentan SUN is too strong or too weak, consult your doctor to check if you need a dose adjustment.

How to take Bosentan SUN

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

If you take more Bosentan SUN than you should

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

If you forget to take Bosentan SUN

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

If you stop taking Bosentan SUN

If you suddenly stop taking Bosentan SUN, your symptoms may worsen. Do not stop taking Bosentan SUN 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 Bosentan SUN are:

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

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

Signs that your liver may not be working properly include:

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

If you have any of these symptoms, consult your doctor immediately

Other side effects:

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

• headache
• edema (swelling of the 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 rash)
• gastroesophageal reflux (acid reflux)
• diarrhea
• syncope (fainting)
• palpitations (rapid or irregular heartbeats)
• low blood pressure
• nasal congestion

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

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

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

• anaphylaxis (generalized allergic reaction), angioedema (swelling, most frequently around the eyes, lips, tongue, or throat)
• liver cirrhosis (fibrosis), liver failure (severe impairment of liver function)

Frequency not known(cannot be estimated from the available data):

• blurred vision

Side effects in children and adolescents

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

Reporting of side effects:

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Bosentan SUN

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 blister after "EXP". The expiry date is the last day of the month stated.

Shelf life after first opening (only for the bottle): 50 days

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 Bosentan SUN 62.5 mg film-coated tablets

• The active ingredient is bosentan. Each tablet contains 62.5 mg of bosentan.
• The other ingredients are corn starch, pregelatinized corn starch, sodium starch glycolate, povidone K-30, glycerol behenate, magnesium stearate.

The film coating (Opadry yellow 21K520019) contains: hypromellose (E464), titanium dioxide (E171), triacetin, talc (E553b), ethylcellulose, yellow iron oxide (E172), red iron oxide (E172).

Appearance of the Product and Package Contents

Bosentan SUN 62.5 mg: film-coated tablets, round, peach or light peach in color, biconvex, marked with "62.5" on one side and smooth on the other side. The tablets have a diameter of approximately 5.9 mm.

PVC/PE/PVdC/Al blisters containing 14 and 56 film-coated tablets.

Unit-dose precut PVC/PE/PVdC/Al blisters containing 14 x 1 and 56 x 1 film-coated tablets

HDPE bottles containing 56 and 100 film-coated tablets.

The HDPE bottles are made of high-density polyethylene, white, opaque, with an induction line and a child-resistant cap, with a silica gel desiccant sachet. The contents of the sachet MUST NOT BE INGESTED.

Only some pack sizes may be marketed.

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

DE: BOSENTAN SUN 62.5 mg Filmtabletten

FR: BOSENTAN SUN 62.5 mg, comprimé pelliculé

IT: Bosentan Sun

ES: Bosentan SUN 62.5 mg film-coated tablets EFG

RO: Bosentan Terapia 62.5 mg film-coated tablets

PL: Bosentan Ranbaxy 62.5 mg

Marketing Authorization Holder:

Sun Pharmaceutical Industries Europe B.V.

Polarisavenue 87

Hoofddorp - 2132JH

Netherlands

Manufacturer

Sun Pharmaceutical Industries Europe B.V.

Polarisavenue 87

Hoofddorp - 2132JH

Netherlands

ALKALOIDA Chemical Company Zrt.

Kabay János u. 29

Tiszavasvári - H-4440

Hungary

Terapia SA

Str. Fabricii nr. 124

Cluj Napoca – 400632

Romania

Local Representative

Sun Pharma Laboratorios, S.L.

Rambla de Catalunya, 53-55

08007 Barcelona

Spain

Tel: +34 93 342 78 90

Date of the Last Revision of this Leaflet:September 2024

Detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products: http://www.aemps.gob.es/.