BOSENTAN SANDOZ FARMACEUTICA 125 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the Patient

Bosentan Sandoz Pharmaceutical 62.5 mg film-coated tablets EFG

Bosentan Sandoz Pharmaceutical 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, 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. See section 4.

Contents of the pack

1. What is Bosentan Sandoz Pharmaceutical and what is it used for
2. What you need to know before you take Bosentan Sandoz Pharmaceutical
3. How to take Bosentan Sandoz Pharmaceutical
4. Possible side effects
5. Storage of Bosentan Sandoz Pharmaceutical
6. Pack contents and further information

1. What is Bosentan Sandoz Pharmaceutical and what is it used for

Bosentan Sandoz Pharmaceutical tablets 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 Sandoz Pharmaceutical 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. Bosentan widens the pulmonary arteries, making it easier for the heart to pump blood through them. This reduces blood pressure and alleviates symptoms.

Bosentan is used for the treatment of 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 marked limitation of physical activity. Some improvements have been observed in patients with PAH class II. 'Class II' implies mild limitation of physical activity. The PAH for which bosentan 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 of the hands and feet) in adult patients suffering from a disease called scleroderma. Bosentan reduces the number of new digital ulcers (on hands and feet) that appear.

2. What you need to know before you take Bosentan Sandoz Pharmaceutical

Do not take Bosentan Sandoz Pharmaceutical

• 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 contraceptive methods. Please read the information in the "Contraceptives" and "Other medicines and Bosentan Sandoz Pharmaceutical" sections,
• if you are taking cyclosporin A(a medicine used after transplants 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 Sandoz Pharmaceutical.

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.

Abnormal liver function tests and anemia have been found in some patients taking bosentan.

Blood tests that 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 (inside the box of Bosentan Sandoz Pharmaceutical tablets). It is essential that you have regular blood tests while taking bosentan. 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 blood tests

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

Anemia blood tests

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

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

Children and adolescents

Bosentan is not recommended in pediatric patients with systemic sclerosis with active digital ulcers. Bosentan should not be used in children with a body weight below 31 kg and pulmonary arterial hypertension. See section 3 "How to take Bosentan Sandoz Pharmaceutical".

Bosentan Sandoz Pharmaceutical with food and drinks

Bosentan Sandoz Pharmaceutical can be taken with or without food.

Other medicines and Bosentan Sandoz Pharmaceutical

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. It is especially important that you tell your doctor if you are taking:

• cyclosporin A (a medicine given after transplants and to treat psoriasis) which must not be given with bosentan,
• sirolimus or tacrolimus, which are medicines given after transplants, and are not recommended to be given with bosentan,
• 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), which are not recommended to be given with bosentan,
• other medicines for the treatment of HIV infection, which may require special monitoring when given with bosentan,
• hormonal contraceptives, which are not effective as the only contraceptive method when taking bosentan. Inside the pack of bosentan, you will find a Patient Alert Card that you should 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).

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Women of childbearing age

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

Pregnancy tests

Bosentan may affect unborn babies 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 you are taking bosentan.

Contraceptives

If you can become pregnant, use a reliable contraceptive method (contraception) while taking bosentan. Your doctor or gynecologist will advise you on reliable contraceptive methods while taking bosentan. Since bosentan can make hormonal contraception less effective (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, contraceptive sponge, or your partner must also use a condom). Inside the pack of bosentan 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 bosentan and being of childbearing age.

Tell your doctor immediately if you become pregnant while taking bosentan, or 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, because it is unknown whether the presence of bosentan in breast milk can harm your baby. Talk to your doctor about this.

Fertility

If you are a man taking bosentan, 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 has no influence or negligible influence on the ability to drive and use machines. Bosentan may cause low blood pressure (hypotension) 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 bosentan, do not drive or operate tools or machinery.

Bosentan Sandoz Pharmaceutical contains sodium

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

3. How to take Bosentan Sandoz Pharmaceutical

Follow exactly the administration instructions of this medicine given by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

Treatment with bosentan should only be started and controlled by a doctor who has experience in the treatment of PAH or systemic sclerosis.

Recommended dose

Adults

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.

Use in children and adolescents

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

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

How to take Bosentan Sandoz Pharmaceutical

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

If you take more Bosentan Sandoz Pharmaceutical than you should

If you have taken more Bosentan Sandoz Pharmaceutical than you should, talk to your doctor, pharmacist, or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount used.

If you forget to take Bosentan Sandoz Pharmaceutical

If you forget 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 make up for forgotten doses.

If you stop taking Bosentan Sandoz Pharmaceutical

If you suddenly stop taking bosentan, your symptoms may worsen. Do not stop taking bosentan 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 product, 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 are:

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

Your liver and blood values will be tested during treatment with bosentan (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 (feeling sick),
• vomiting,
• fever (high temperature),
• stomach pain (abdomen),
• 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 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 in the blood),
• neutropenia/leukopenia (low white blood cell count in the blood),
• elevated liver function tests with hepatitis (inflammation of the liver) including possible exacerbation of underlying hepatitis and/or jaundice (yellowing of the skin or whites of the eyes).

Rare(may affect up to 1 in 1,000people):

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

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 bosentan are the same as in adults.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any 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 Sandoz Pharmaceutical

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 shown.

No special storage conditions are required.

Medicines should not be disposed of via wastewater or household waste. Return any unused medicine to your pharmacist. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Bosentan Sandoz Pharmaceutical

Bosentan Sandoz Pharmaceutical 62.5 mg film-coated tablets:

• The active ingredient is bosentan (as monohydrate).

Each film-coated tablet contains 62.5 mg of bosentan (corresponding to 64.541 mg of bosentan monohydrate).

• Other components(excipients) are:

Tablet core: corn starch, pregelatinized corn starch, sodium carboxymethyl potato starch (type A), povidone K 30, poloxamer 188, colloidal anhydrous silica, glycerol dibehenate, and magnesium stearate.

Coating: Opadry orange 21K23007 (contains hypromellose, titanium dioxide (E171), ethylcellulose, triacetin (E 1518), talc (E 553b), yellow iron oxide (E172), red iron oxide (E172), and black iron oxide (E172).

Bosentan Sandoz Pharmaceutical 125 mg film-coated tablets:

• The active ingredient is bosentan (as monohydrate).

Each film-coated tablet contains 125 mg of bosentan (corresponding to 129.082 mg of bosentan monohydrate).

• Other components(excipients) are:

Tablet core: corn starch, pregelatinized corn starch, sodium carboxymethyl potato starch (type A), povidone K 30, poloxamer 188, colloidal anhydrous silica, glycerol dibehenate, and magnesium stearate.

Coating: Opadry orange 21K23007 (contains hypromellose, titanium dioxide (E171), ethylcellulose, triacetin (E 1518), talc (E 553b), yellow iron oxide (E172), red iron oxide (E172), and black iron oxide (E172).

Product Appearance and Package Contents

Bosentan Sandoz Pharmaceutical 62.5 mg are light orange, round, biconvex film-coated tablets, 6 mm in size.

Bosentan Sandoz Pharmaceutical 125 mg are light orange, oval, biconvex film-coated tablets, 11x5 mm in size.

The film-coated tablets are presented in PVC/PVDC-Aluminum blisters inside a cardboard box.

Package sizes:

14, 56, or 112 film-coated tablets.

Not all package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Sandoz Pharmaceutical, S.A.

Centro Empresarial Parque Norte

Edificio Roble

C/ Serrano Galvache, 56

28033 Madrid

Spain

Manufacturer

Lek Pharmaceuticals d.d.

Verovškova ulica 57,

1526 Ljubljana

Slovenia

or

Salutas Pharma GmbH

Otto-von-Guericke-Allee 1

39179 Barleben

Germany

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

Austria: Bosentan Sandoz 125 mg - Filmtabletten

Belgium: Bosentan Sandoz 62,5 mg filmomhulde tabletten

Bosentan Sandoz 125mg filmomhulde tabletten

Bulgaria: Bosentan SDZ 125 mg ????????? ????????

Germany: Bosentan HEXAL 62,5 mg Filmtabletten

Bosentan HEXAL 125 mg Filmtabletten

Netherlands: Bosentan Sandoz 62,5 mg, filmomhulde tabletten

Bosentan Sandoz 125 mg, filmomhulde tabletten

Norway: Bosentan Sandoz 62.5 mg, tablett, filmdrasjert

Bosentan Sandoz 125 mg, tablett, filmdrasjert

Poland: Bosentan Sandoz GmbH, 125 mg, tabletki powlekane

Portugal: Bosentano Sandoz 62.5 mg Comprimido revestido por película

Bosentano Sandoz 125 mg Comprimido revestido por película

Sweden: Bosentan Sandoz 62,5 mg filmdragerade tabletter

Bosentan Sandoz 125 mg filmdragerade tabletter

Date of the last revision of this leaflet: January 2025

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

Patient Alert Card