Package Insert: Information for the Patient

Bosentan Accordpharma 125 mg Film-Coated Tablets

Read this package insert carefully before starting to take this medication, as it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed only for you and should not be given to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert.

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

Bosentan Accordpharma is used to treat:

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

• primary (in which the cause or hereditary is not identified);
• caused by scleroderma (also known as 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 (at birth) with shunts (abnormal communications) that cause abnormal blood flow between the heart and lungs.

Do not take Bosentan Accordpharma:

• if you are allergic to bosentanor 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 could be pregnantas you are not using a reliable method of contraception. Please read the information in the section “Contraceptives” and “Other medicines and Bosentan Accordpharma”
• if you are taking ciclosporin A(a medicine used after a transplant or to treat psoriasis)

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

Warnings and precautions

Consult your doctor or pharmacist before taking bosentan.

Tests your doctor will perform before prescribing treatment

• a blood test to assess liver function
• a blood test to detect if there is anaemia (low haemoglobin)
• a pregnancy test if you are a fertile woman

Abnormalities in liver function tests and anaemia (low haemoglobin) have been found in some patients taking bosentan.

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 haemoglobin levels.

Please refer to the Patient Alert Card (inside the bosentan packaging) for these tests. It is essential to perform regular blood tests while taking bosentan. We suggest you write the date of the most recent test and your next test date (ask your doctor for the date) on the patient alert card to help you remember when your next appointment is.

Liver function tests

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

Haemoglobin tests

These tests will be performed monthly for the first 4 months of treatment and then every 3 months, as patients taking bosentan may develop anaemia.

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

Children and adolescents

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

Other medicines and Bosentan Accordpharma

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medicine, including those obtained without a prescription. It is especially important to inform your doctor if you take:

• ciclosporin A (a medicine used after transplants and to treat psoriasis), which should not be administered with bosentan.
• sirólimus or tacrólimus, which are medicines used after transplants, and it is not recommended to administer them with bosentan.
• glibenclamida (a medicine for diabetes), rifampicina (a medicine for tuberculosis), fluconazol (medicines for fungal infections), ketoconazol (a medicine used to treat Cushing's syndrome), or nevirapina (a medicine for HIV), as it is not recommended to administer these medicines with bosentan.
• other medicines for HIV infection treatment, which may require special monitoring when administered with bosentan.
• oral contraceptives, which are not effective as the sole method of contraception when taking bosentan. Inside the bosentan packaging, you will find a Patient Alert Card that you must read carefully. Your doctor and/or gynaecologist will determine the suitable contraceptive method for you.
• other medicines for pulmonary hypertension treatment: sildenafilo and tadalafilo:
• warfarina (an anticoagulant);
• simvastatina (used to treat hypercholesterolemia).

Driving and operating machinery

Bosentan has no influence or insignificant influence on driving and operating machinery. However, bosentan may induce hypotension (blood pressure decrease) that may cause dizziness, affect your vision, and affect your ability to drive and operate machinery. Therefore, if you feel dizzy or see blurry while taking bosentan, do not drive or operate tools or machinery.

Fertile women

DO NOT take bosentan if you are pregnant or plan to become pregnant

Pregnancy tests

Bosentan may affect unborn babies conceived before or during treatment. If you are a fertile woman, your doctor will ask you to perform a pregnancy test before starting bosentan treatment and regularly while taking bosentan.

Contraceptives

If you may become pregnant, use a reliable method of contraception (contraception) while taking bosentan. Your doctor or gynaecologist will advise you on suitable contraceptive methods while taking bosentan. Since bosentan may make hormonal contraception ineffective (e.g., oral, injection, implant, or skin 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, spermicide, or your partner must also use a condom). Inside the bosentan packaging, you will find a Patient Alert Card that you must read carefully. You must complete this card and bring it to your doctor's next visit so that your doctor or gynaecologist can determine if you need an alternative or additional reliable contraceptive method. It is recommended to perform a pregnancy test monthly while taking bosentan and are fertile.

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

Breastfeeding

Bosentan passes into breast milk.It is recommended to stop breastfeeding if you are prescribed bosentan, as it is unknown if the presence of bosentan in breast milk may harm your baby.

Inform your doctorimmediately if you arebreastfeeding.

Fertility

If you are a man and takingbosentan, it is possible that this medicine may decrease your sperm count. It cannot be ruled out that it may affect your ability to father a child. Discuss any concerns or doubts with your doctor.

The treatment with bosentan 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 medication indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

Use of Bosentan Accordpharma with food and beverages

Bosentan can be administered with or without food.

The recommended dose is

Adult

The treatment in adults usually starts with 62.5 mg twice a day (morning and night) for the first 4 weeks, after which your doctor will normally advise you to take one 125 mg tablet twice a day, depending on how you react to bosentan.

Children and adolescents

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

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

How to take Bosentan Accordpharma

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

If you take more Bosentan Accordpharma than you should

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

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

If you forgot to take Bosentan Accordpharma

If you forgot to take bosentan, take the dose as soon as you remember and then continue taking it at your usual time. Do not take a double dose to compensate for the missed doses.

If you interrupt the treatment with Bosentan Accordpharma

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

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

The most serious side effects with bosentan are:

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

Your liver and blood values will be analyzed during treatment with bosentan (see section 2). It is essential to have these analyses done as prescribed by your doctor.

The signs that your liver may not be functioning correctly include:

• Nausea (need to vomit)
• Vomiting
• Fever (elevated temperature)
• Abdominal pain (stomach pain)
• Ictericia (yellowish color of the skin or the white of the eyes)
• Dark-colored urine
• Itching (pruritus)
• Letargo or fatigue (unusual or excessive tiredness)
• Pseudo-gripal syndrome (joint and muscle pain with fever)

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

Other side effects:

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

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

Common (can affectup to 1 in 10people):

• Rubefaction (skin redness)
• Hypersensitivity reactions (including skin inflammation, itching, and rash)
• Gastroesophageal reflux (acid reflux)
• Dyspepsia (diarrhea)
• Syncope (fainting)
• Palpitations (rapid or irregular heartbeats)
• Low blood pressure
• Nasal congestion

Uncommon(can affectup to 1 in 100people):

• Trombocytopenia (decreased platelet count in the blood)
• Neutropenia/leucopenia (decreased white blood cell count)
• Abnormal liver function tests with hepatitis (inflammation of the liver) including a possible exacerbation of hepatitis and/or ictericia (yellowish color of the skin or the white of the eyes)

Rare(can affectup to 1 in 1000people):

• Anaphylaxis (generalized allergic reaction), angioedema (swelling, often around the eyes, lips, tongue, or throat)
• Cirrhosis (fibrosis) of the liver, liver failure (severe alteration of liver function)

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

Side effects in children and adolescents

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

Reporting of side effects:

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: https://www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the box and on the blister after "EXP". The expiration date is the last day of the month indicated.

Aluminum-aluminum blister

No special storage conditions are required.

PVC/PE/PVDC-aluminum blister

Do not store at a temperature above 30°C.

Medicines should not be disposed of through drains or in the trash. Dispose of packaging and unused medications at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of unused packaging and medications. By doing so, you will help protect the environment.

Composition of Bosentan Accordpharma

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

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

Appearance of the product and contents of the pack

Bosentan Accordpharma 125 mg are oval-shaped, biconvex, film-coated tablets, with the mark “IB2” on one face and smooth on the other face.

Blister packs containing 56 film-coated tablets.

Marketing authorisation holder:

Accord Healthcare S.L.U.

World Trade Center.

Moll de Barcelona, s/n,

Edifici Est, 6th floor.

08039, Barcelona

Spain

Responsible for manufacturing

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, 3526KV,

Netherlands

Last date of revision of this leaflet: February 2025

The detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS):http://www.aemps.gob.es/

PATIENT ALERT CARD