Bosentan AccordPharma 125 mg film-coated tablets EFG

Patient Information Leaflet

Introduction

Package leaflet: Information for the patient

Bosentan Accordpharma 125 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, 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 other people, even if they have the same symptoms as you, because 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 Bosentan Accordpharma is and what it is used for
2. What you need to know before taking Bosentan Accordpharma
3. How to take Bosentan Accordpharma
4. Possible side effects
5. How to store Bosentan Accordpharma
6. Contents of the pack and other information

1. What is Bosentan Accordpharma and what is it used for?

Bosentan Accordpharma tablets contain bosentan, which blocks the natural hormone called endothelin-1 (ET-1), a substance that causes narrowing of blood vessels. Bosentan therefore causes blood vessels to dilate and belongs to a class of medicines known as “endothelin receptor antagonists”.

Bosentan Accordpharma 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 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. Bosentan widens the pulmonary arteries, making it easier for the heart to pump blood through them. This reduces blood pressure and relieves symptoms.

Bosentan is used to treat patients with pulmonary arterial hypertension (PAH) in WHO 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’ means marked limitation in physical activity. Some improvements have also been observed in patients with PAH class II. ‘Class II’ means slight limitation in physical activity. The PAH for which Bosentan is indicated may be:

• primary (in which no cause is identified or is hereditary);

• caused by scleroderma (also called systemic sclerosis, a disease in which there is 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. Bosentan reduces the number of new digital ulcers (in hands and feet) that develop.

2. What you need to know before taking Bosentan Accordpharma

Do not take Bosentan Accordpharma:

• if you are allergic to bosentan or to 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 might be pregnant due to not using reliable contraceptive methods. Please read the information in the sections “Contraceptives” and “Other medicines and Bosentan Accordpharma”
• if you are taking cyclosporine A (a medicine used after organ transplant or to treat psoriasis)

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

Warnings and precautions

Talk to your doctor or pharmacist before taking bosentan.

Tests your doctor will perform before prescribing the 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

Abnormal liver function tests and anemia (low hemoglobin) have been observed in some patients taking bosentan.

Blood tests your doctor will perform during treatment

During treatment with bosentan, 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 box of bosentan tablets). It is important that you undergo regular blood tests while taking bosentan. 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 bosentan. After a dose increase, an additional test should 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 bosentan may develop anemia.

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

Children and adolescents

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

Other medicines and Bosentan Accordpharma

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines, even 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 to treat psoriasis), which must not be taken together with bosentan.
• sirolimus or tacrolimus, which are medicines used after organ transplantation, and are not recommended to be taken together with bosentan.
• glibenclamide (a medicine for diabetes), rifampicin (a medicine for tuberculosis), fluconazole (medicines for fungal infections), ketoconazole (a medicine used to treat Cushing's syndrome), or nevirapine (a medicine for HIV), as these medicines are not recommended to be taken together with bosentan.
• other medicines for the treatment of HIV infection, which when taken together with bosentan may require special monitoring.
• oral contraceptives, which are not effective as the sole method of contraception when taking bosentan. Inside the Bosentan Accordpharma 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 using machines

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

Women of childbearing potential

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

Pregnancy tests

Bosentan 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 bosentan, and regularly while taking bosentan.

Contraception

If you could become pregnant, use a reliable method of contraception (contraception) while taking bosentan. Your doctor or gynecologist will advise you on reliable contraceptive methods while taking bosentan. Since bosentan 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 contraceptives, you must also use a barrier method (e.g., female condom, diaphragm, contraceptive sponge, or your partner should use a male condom). Inside the box of bosentan tablets, 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 taking bosentan if you are of childbearing age.

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

Breast-feeding

Bosentan passes into breast milk. You are advised to stop breast-feeding if you are prescribed bosentan, as it is unknown whether bosentan in breast milk could harm your baby.

Inform your doctor immediately if you are breast-feeding.

Fertility

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

3. How to take Bosentan Accordpharma

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

Taking Bosentan Accordpharma with food and drink

Bosentan 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 take one 125 mg tablet twice daily, depending on how you respond to bosentan.

Children and adolescents

The recommended dose in children applies only for PAH. For children aged 1 year and older, treatment with bosentan 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 bosentan is too strong or too weak, consult your doctor to determine whether a dose adjustment is needed.

How to take Bosentan Accordpharma

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

If you take more Bosentan Accordpharma than you should

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

In case of overdose or accidental ingestion, go immediately to a medical center or call the Toxicology Information Service (telephone 91 562 04 20), indicating the medicine and the amount ingested.

If you forget to take Bosentan Accordpharma

If you forget to take bosentan, take the missed dose 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 Bosentan Accordpharma

If you stop treatment with bosentan suddenly, your symptoms may worsen. Do not stop taking bosentan unless your doctor tells you to. Your doctor may instruct you to gradually reduce the dose over several days before stopping it 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 cause adverse effects, although not everyone experiences them.

The most serious adverse effects with bosentan are:

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

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

Signs that your liver may not be working properly include:

• Nausea (feeling like vomiting)
• Vomiting
• Fever (high temperature)
• Stomach (abdominal) pain
• Jaundice (yellowing of the skin or whites 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 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 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 swelling, 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 worsening 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), autoimmune hepatitis (liver inflammation caused by the body's own immune system attacking liver cells), which may occur even several months to years after starting treatment

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 bosentan 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 can also report them directly through the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Bosentan Accordpharma

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 blister pack following "EXP". The expiry date refers to the last day of the month indicated.

Aluminium-aluminium blister

No special storage conditions are required.

PVC/PE/PVDC-aluminium blister

Do not store above 30°C.

Medicines must not be disposed of via wastewater or household waste. Unused medicines and their containers should be returned to a SIGRE collection point at your pharmacy. If you are unsure, ask your pharmacist how to dispose of unused medicines and their packaging. This will help protect the environment.

6. Contents of the pack and other information

Composition of Bosentan Accordpharma

• Bosentan Accordpharma 125 mg film-coated tablets: The active substance is bosentan monohydrate. Each tablet contains 125 mg of bosentan (as monohydrate).

• Other components of the tablet core: maize starch, pregelatinized starch (maize), sodium carboxymethyl starch from potato, povidone, and magnesium stearate. The film coating contains hypromellose, triacetin, talc, titanium dioxide (E171), yellow iron oxide (E172), and red iron oxide (E172).

Appearance of the product and contents of the pack

Bosentan Accordpharma 125 mg are light orange, oval-shaped, biconvex, film-coated tablets, marked "IB2" on one side and smooth on the other.

Blister packs containing 56 film-coated tablets.

Marketing Authorization Holder:

Accord Healthcare S.L.U.

World Trade Center

Moll de Barcelona, s/n

Edifici Est, 6th floor

08039, Barcelona

Spain

Manufacturer:

Laboratori Fundació DAU

C/ C, 12-14 Pol. Ind. Zona Franca

08040 (Barcelona), Spain

or

Accord Healthcare Polska Sp. z o.o.

ul. Lutomierska 50, 95-200 Pabianice

Poland

or

Accord Healthcare B.V.

Winthontlaan 200, Utrecht, 3526 KV

The Netherlands

or

Accord Healthcare Single Member S.A.

64th Km National Road Athens

Lamia, Schimatari, 32009, Greece

Date of latest revision of this leaflet: November 2025

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

PATIENT ALERT CARD