Package Insert: Information for the Patient

Bosentan Sandoz Pharmaceutical 62.5 mg Film-Coated Tablets

Bosentan Sandoz Pharmaceutical 125 mg Film-Coated Tablets

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

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult yourdoctor or pharmacist.
• This medication has been prescribedonlyfor you, and you should not give it to others even if they havethe same symptomsas you,as it may harm them.
• If you experience any adverse effects,consult your doctor or pharmacist,evenif they are not listed in this package insert. See section 4.

The Bosentan Sandoz Farmacéutica 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 Sandoz Farmacéutica is used to treat:

• Pulmonary arterial hypertension (PAH):PAH is a serious narrowing of the blood vessels in the lungs, resulting in 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 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. 'Class II' implies a slight limitation of physical activity. The 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.

• Digital ulcers:(ulcers on the fingers of the hands and feet) in adult patients with a disease called scleroderma. Bosentan reduces the number of new digital ulcers (on hands and feet) that appear.

Do not take BosentanSandoz Farmacéutica

• if you are allergic to bosentanor to any of the other ingredients ofthis 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 section “Contraceptives” and “Other medicines and Bosentan Sandoz Farmacéutica”,
• 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 starting to take BosentanSandoz Farmacéutica.

Tests your doctor will perform before prescribing the treatment

• a blood test to assess liver function,
• a blood test to detect if there is anemia (low hemoglobin),
• a pregnancy test if you are a fertile woman.

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

Tests your doctor will perform during the treatment

During treatment with bosentan, your doctor will schedule regular blood tests to monitor changes in your liver function and hemoglobin levels.

Please refer to the Patient Alert Card (inside the BosentanSandoz Farmacéuticapackaging). It is essential to perform regular blood tests while taking bosentan. We recommend that you write the date of the most recent test and your next test (ask your doctor for the date) on the Patient Alert Card, to help you remember when your next visit is.

Liver function tests

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

Anemia 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 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 for pediatric patients with systemic sclerosis and active digital ulceration. Bosentan should not be used in children with a body weight below 31 kg and pulmonary arterial hypertension. See section 3 “How to take BosentanSandoz Farmacéutica”.

Bosentan Sandoz Farmacéutica with food and drinks

Bosentan Sandoz Farmacéutica can be taken with or without food.

Other medicines and BosentanSandoz Farmacéutica

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medicine. It is especially important to inform your doctor if you are taking:

• ciclosporin A (a medicine used after transplants and to treat psoriasis) that should not be administered with bosentan,
• sirolimus or tacrolimus, which are medicines used after transplants, and it is not recommended to administer them with bosentan,
• glibenclamide (a diabetes medicine), rifampicin (a tuberculosis medicine), fluconazole (an antifungal medicine), ketoconazole (a medicine used to treat Cushing's syndrome), or nevirapine (an HIV medicine), as it is not recommended to administer these medicines with bosentan,
• other medicines for the treatment of HIV infection, which when administered with bosentan may require special monitoring,
• hormonal contraceptives, which are not effective as the sole method of contraception when taking bosentan. Inside the packaging 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 arterial hypertension: sildenafil and tadalafil,
• warfarin (an anticoagulant),
• simvastatin (used to treat hypercholesterolemia).

Pregnancy,breastfeedingand fertility

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medicine.

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 undergo 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. Your doctor or gynecologist will advise you on reliable contraceptive methods while taking bosentan. Since bosentan may make hormonal contraceptives 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 should read carefully. Your doctor and/or gynecologist will 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 discontinue breastfeeding if you are prescribed bosentan, as it is unknown if the presence of bosentan in breast milk may harm your baby. Talk to your doctor about this.

Fertility

If you are a man taking bosentan, 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. Talk to your doctor if you have any doubts or concerns about this.

Driving and operating machinery

Bosentan has no influence or this is insignificant on driving and operating machinery. Bosentan may induce hypotension (low blood pressure) 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.

Bosentan Sandoz Farmacéutica contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per coated tablet; it is essentially “sodium-free”.

Follow exactly the administration instructions of this medication as indicated by your doctor or pharmacist.This medication should be taken exactly as directed.If you are unsure, consult your doctor or pharmacist again.

The treatment with bosentan should only be initiated and monitored by a doctor with experience in the treatment of HAP or systemic sclerosis.

Recommended Dose

Adults

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.

Use in Children and Adolescents

The recommended dose in children is only for HAP. For children over 1 year of age, the treatment with bosentan usually starts with 2 mg per kg of body weight twice a day (morning and night). 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 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 Sandoz Farmacéutica

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

If You Take More Bosentan Sandoz Farmacéutica Than You Should

If you have taken more Bosentan Sandoz Farmacéutica than you should, consult your doctor, pharmacist, or call the Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount used.

If You Forget to Take Bosentan Sandoz Farmacéutica

If you forget to take bosentan, take the dose as soon as you remember and continue taking it at your regular schedule.Do not take a double dose to compensate for the missed doses.

If You Interrupt Treatment with Bosentan Sandoz Farmacéutica

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 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 up to 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,
• Jaundice (yellowish color of the skin or white of the eyes),
• Dark-colored urine,
• Itching,
• Lethargy 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 affectmore 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):

• 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(can affectup to 1 in 100people):

• Thrombocytopenia (decreased platelet count in the blood),
• Neutropenia/leucopenia (decreased white blood cell count),
• Elevated liver function tests with hepatitis (inflammation of the liver) including a possible exacerbation of underlying hepatitis and/or jaundice (yellowish color of the skin or 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 side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through theSistema Español de Farmacovigilancia de medicamentos de Uso Humano:https://www.notificaram.es.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keepthis medicationout of the sight and reach of children.

Do not usethis medicationafter the expiration date that appears onthe packagingand the blisterafter CAD/EXP. The expiration date is the last day of the month indicated.

No special storage conditions are required.

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

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).

• The other components(excipients)are:

Tablet core: maize starch, pregelatinized maize starch, sodium carboxymethyl starch (type A), povidone K 30, poloxamer 188, anhydrous colloidal silica, dibehenate of glycerol, 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 Pharmaceutical125 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).

• The other components(excipients)are:

Tablet core: maize starch, pregelatinized maize starch, sodium carboxymethyl starch (type A), povidone K 30, poloxamer 188, anhydrous colloidal silica, dibehenate of glycerol, 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)).

Appearance of the product and contents of the pack

Bosentan Sandoz Pharmaceutical 62.5 mg are orange-yellow, round, biconvex, and 6 mm film-coated tablets.

Bosentan Sandoz Pharmaceutical 125 mg are orange-yellow, oval, biconvex, and 11x5 mm film-coated tablets.

Film-coated tablets are presented in PVC/PVDC-Aluminium blisters inside a cardboard box.

Pack sizes:

14, 56, or 112 film-coated tablets.

Only some pack sizes may be marketed.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Sandoz Pharmaceutical, S.A.

Centro Empresarial Parque Norte

Edificio Roble

C/ Serrano Galvache, 56

28033 Madrid

Spain

Responsible for manufacturing

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 with 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

Last revision date of thisleaflet: January 2025

For detailed information about this medicinal product, please consult the website of the Spanish Agency of Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/

Patient alert card