BOSENTAN AUROVITAS 125 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

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

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

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

Bosentan 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 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 marked limitation of physical activity. Some improvements have been observed in patients with PAH class II. The "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 Aurovitas

Do not take Bosentan Aurovitas

• 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 because you are not using reliable contraceptive methods. Read the information in the "Contraceptives" and "Other medicines and Bosentan Aurovitas" sections.
• if you are taking ciclosporin A (a medicine used after transplants or to treat psoriasis).

If any of the above applies to you, tell your doctor.

Warnings and precautions

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

Tests that your doctor will perform before treatment

• a blood test to check liver function.
• a blood test to check for 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.

Tests that your doctor will perform during treatment

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

For all these tests, see also the Patient Alert Card (inside the box of Bosentan Aurovitas tablets). It is essential that you have these regular blood tests while taking bosentan. We suggest that you write the date of the most recent test and the date of your next test (ask your doctor for the date) on the Patient Alert Card to help you remember when your next visit is.

Blood tests for liver function

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.

Blood tests for anemia

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 are abnormal, your doctor may decide to reduce the dose or stop 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. See also section 3. How to take Bosentan Aurovitas.

Other medicines and Bosentan Aurovitas

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription. It is especially important that you tell your doctor if you are taking:

• ciclosporin A (a medicine used after transplants or to treat psoriasis) which must not be taken with bosentan.
• sirolimus or tacrolimus, which are medicines used after transplants, and are not recommended to be taken 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 taken with bosentan.
• other medicines for the treatment of HIV infection, which may require special monitoring when taken with bosentan.
• oral contraceptives, which are not effective as the only contraceptive method when taking bosentan. Inside the pack of Bosentan Aurovitas 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).

Taking Bosentan Aurovitas with food, drinks, and alcohol

Bosentan can be taken with or without food.

Pregnancy, breastfeeding, and fertility

Women of childbearing age

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

Pregnancy tests

Bosentan 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 it.

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 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 pack of Bosentan Aurovitas, 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.

Breastfeeding

Bosentan passes into breast milk. You are advised to stop breastfeeding 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

The influence of bosentan on the ability to drive and use machines is negligible. However, bosentan can cause hypotension (low blood pressure) 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 Aurovitas 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 Aurovitas

Treatment with bosentan should only be started and controlled by a doctor who has experience in the treatment of PAH or systemic sclerosis. Follow the instructions for administration of this medicine exactly as indicated by your doctor. If you are in doubt, consult your doctor or pharmacist again.

The recommended dose is:

Adults

Treatment in adults usually starts with 62.5 mg twice a day (morning and evening) for the first 4 weeks; after that, your doctor will usually 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, treatment with bosentan usually starts with 2 mg per kg of body weight twice a day (morning and evening). Your doctor will advise you on the dose.

Remember that other formulations of bosentan are available, which may facilitate dosing in children and patients with low weight or difficulty swallowing film-coated tablets.

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

How to take Bosentan Aurovitas

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

If you take more Bosentan Aurovitas than you should

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

In case of overdose or accidental ingestion, talk to your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medicine and the amount taken.

If you forget to take Bosentan Aurovitas

If you forget to take the medicine, 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 Aurovitas

If you suddenly stop treatment with 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 other questions about 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 are:

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

Your liver and blood values will be checked 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 (need to vomit).
• vomiting.
• fever (high temperature).
• stomach pain (abdomen).
• jaundice (yellowing of the skin or the whites of the eyes).
• dark-colored urine.
• itching of the skin.
• lethargy or fatigue (unusual tiredness or exhaustion).
• pseudoflu 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 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 100people):

• 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 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 (the 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, even if it is possible side effects that are not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Bosentan Aurovitas

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.

This medicine does not require any special storage conditions.

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. Container Content and Additional Information

Composition of Bosentan Aurovitas

• The active ingredient is bosentan (as monohydrate). Each film-coated tablet contains 125 mg of bosentan (as monohydrate).
• The other components are:

Core of the tablet:pregelatinized corn starch, corn starch, sodium carboxymethyl starch (type A) (potato), crospovidone (type B), povidone (K-90), glycerol dibehenate, magnesium stearate.

Coating:hypromellose (E464), ethylcellulose, triacetin, talc, titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172).

Appearance of the Product and Container Content

Orange-white, oval, biconvex film-coated tablets, marked with “K” on one side and “22” on the other, separated by a score line. The tablet can be divided into equal doses. The size is 11.2 mm × 5.2 mm.

Bosentan Aurovitas film-coated tablets are available in white opaque PVC/PE/PVdC-Aluminum blister packs and HDPE bottles with polypropylene closures.

Container sizes:

In blisters: 14, 28, 30, 50, 56, 60, 90, 98, 112, and 120 film-coated tablets.

In bottles: 30, 100, and 1,000 film-coated tablets.

Only some container sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Aurovitas Spain, S.A.U.

Avda. de Burgos, 16-D

28036 Madrid

Spain

Manufacturer:

APL Swift Services (Malta) Limited

HF26, Hal Far Industrial Estate, Hal Far

Birzebbugia, BBG 3000

Malta

Or

Orion Corporation

Orion Pharma

Orionintie 1

FI-02200 Espoo

Finland

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

Date of the Last Revision of this Leaflet: December 2024

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/).