BOSENTAN NORMON 125 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Bosentan Normon 125 mg film-coated tablets EFG

bosentan

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.

Contents of the pack

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

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

Bosentan Normon 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 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 decreases 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 or hereditary is identified),
• 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 (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 Normon reduces the number of new ulcers (on hands and feet) that appear.

2. What you need to know before you take Bosentan Normon

Do not take Bosentan Normon:

• if you are allergic to bosentanor to any of the other ingredients of this medicine (included in section 6).
• if you have liver problems(ask your doctor).
• if you are pregnant, or could be pregnantby not using reliable contraceptive methods. Please read the information in the section "Contraceptives" and "Other medicines and Bosentan Normon".
• 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 to take Bosentan Normon.

Tests that your doctor will perform before prescribing the 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.

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

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 Normon 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.

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 during the first 4 months of treatment and subsequently 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 Normon 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 Normon.

Other medicines and Bosentan Normon

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

• cyclosporin A (a medicine used after transplants or to treat psoriasis) that must not be administered with bosentan.
• sirolimus or tacrolimus, which are medicines used after transplants, and are not recommended to be administered 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) as these medicines are not recommended to be administered with bosentan.
• other medicines for the treatment of HIV infection, which may require special monitoring when administered with bosentan.
• oral contraceptives, which are not effective as the only contraceptive method when taking bosentan. Inside the pack of Bosentan Normon, you will find a Patient Alert Card that you must read carefully. Your doctor and/or gynecologist will establish 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).

Pregnancy, breastfeeding, and fertility

Women of childbearing age

DO NOT take Bosentan Normon if you are pregnant or plan 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 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 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 Normon, 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

Tell your doctorimmediately if you are breastfeeding. It is recommended to interrupt breastfeeding if you are prescribed bosentan, as it is not known whether this medicine passes into breast milk.

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. However, bosentan may 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 Normon 125 mg film-coated tablets EFG contains sodium

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

3. How to take Bosentan Normon

Treatment with Bosentan Normon should only be started and controlled by a doctor who has experience in the treatment of PAH or systemic sclerosis. Follow exactly the instructions of administration of this medicine indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

Use of Bosentan Normon with food and drinks

Bosentan Normon can be taken with or without food.

The recommended dose is:

Adult

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, 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 Normon

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

If you take more Bosentan Normon than you should

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

If you forget to take Bosentan Normon

If you forget to take Bosentan Normon, take the dose as soon as you remember and then continue taking it at your usual schedule. Do not take a double dose to make up for forgotten doses.

If you stop taking Bosentan Normon

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 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 that may affect more than 1 in 10 people.
• Anemia (low blood value) that may affect up to 1 in 10 people. Anemia may occasionally require 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 (need to vomit).
• vomiting.
• fever (high temperature).
• stomach pain (abdomen).
• jaundice (yellowing of the skin or the white of the eyes).
• dark urine.
• itching of the skin.
• lethargy or fatigue (unusual tiredness or exhaustion).
• Pseudogrippal syndrome (joint and muscle pain with fever).

If you have any of these symptoms, consult 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.
• 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/leucopenia (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 white of the eyes).

Rare(may affect up to 1 in 1000people):

• anaphylaxis (generalized allergic reaction), angioedema (swelling, most frequently 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, pharmacist, or nurse, even if it is possible that they are 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 Normon

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 on the blister after "EXP:". The expiry date is the last day of the month shown.

This medicine does not require any special storage conditions.

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

6. Contents of the pack and further information

Composition of Bosentan Normon 125 mg film-coated tablets

• The active substance is bosentan monohydrate. Each tablet contains 125 mg of bosentan (as monohydrate).

• The other ingredients are: pregelatinized corn starch, sodium carboxymethyl potato starch type A, colloidal anhydrous silica, povidone, magnesium stearate, hypromellose, macrogol 6000, talc, titanium dioxide (E171), yellow iron oxide (E172), and red iron oxide (E172).

Appearance of the product and pack contents

Bosentan Normon 125 mg are film-coated tablets, elongated, biconvex, and of a pale orange color.

Bosentan Normon 125 mg film-coated tablets are available in packs of 14, 56, or 112 tablets in aluminum/aluminum-polyamide-PVC or aluminum/PVDC-PE blisters.

Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

LABORATORIOS NORMON, S.A.

C/ Ronda de Valdecarrizo, 6

28760 Tres Cantos, Madrid

Spain

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

Portugal: Bosentano Normon 125 mg film-coated tablets

Date of last revision of this leaflet:June 2021

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