Package Insert: Information for the User

Bosentan Normon 125 mg Film-Coated Tablets

bosentan

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 refer to 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 Normon 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 is used to treat:

• Pulmonary arterial hypertension(PAH): PAH is a severe 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. The ‘class II’ implies a mild 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.

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.

Do not take Bosentan Normon:

• 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 reliable contraceptive methods. Please read the information in the section “Contraceptives” and “Other medicines and Bosentan Normon”.
• 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 Bosentan Normon.

Tests your doctor will perform before prescribing the 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 have been found in some patients taking Bosentan Normon.

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 haemoglobin levels.

Please refer to the Patient Alert Card (inside the Bosentan Normon tablet box) for further information. 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 date (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.

Anaemia 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 treatment with Bosentan Normon 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 also section 3. How to take Bosentan Normon.

Other medicines and Bosentan Normon

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

• ciclosporin A (a medicine administered after transplants and to treat psoriasis) which should not be administered with bosentan.
• sirolimus or tacrolimus, which are medicines administered after transplants, and it is not recommended to administer them 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 it is not recommended to administer these medicines with bosentan.
• other medicines for the treatment of HIV infection, which administered with bosentan may require special monitoring.
• oral contraceptives, which are not effective as the sole method of contraception when taking bosentan. Inside the Bosentan Normon tablet box, you will find a Patient Alert Card that you should read carefully. Your doctor and/or gynaecologist will determine an alternative or additional reliable contraceptive method for you.
• other medicines for the treatment of pulmonary hypertension: sildenafil and tadalafil.
• warfarin (an anticoagulant).
• simvastatin (used to treat hypercholesterolaemia).

Pregnancy, breastfeeding and fertility

Fertile women

DO NOT take Bosentan Normon 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 fertile woman, your doctor will ask you to perform a pregnancy test before starting treatment with bosentan, 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 reliable contraceptive methods while taking bosentan. Since bosentan may make hormonal contraception ineffective (e.g. oral, injection, implant, or skin patch), this method alone is not reliable. Therefore, if you use hormonal contraceptives, you should also use a barrier method (e.g. female condom, diaphragm, spermicide, or your partner should also use a condom). Inside the Bosentan Normon tablet box, you will find a Patient Alert Card that you should complete and bring 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

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

Fertility

If you are a man taking bosentan, it is possible that this medicine may reduce 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.

Driving and operating machinery

Bosentan has no influence or has a negligible influence on driving and operating machinery. However, bosentan may cause hypotension (low blood pressure) which may cause dizziness, affect your vision, and affect your ability to drive and operate machinery. Therefore, if you feel dizzy or see blurred vision while taking bosentan, do not drive or operate machinery.

Bosentan Normon 125 mg film-coated tablets contain sodium

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

Bosentan Normon treatment should only be initiated and monitored by a doctor experienced in treating pulmonary arterial hypertension (PAH) or systemic sclerosis. Follow exactly the administration instructions for this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

Use of Bosentan Normon with food and beverages

Bosentan Normon can be taken with or without food.

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 aged 1 year or older, bosentan treatment 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 continue taking it at your usual schedule. Do not take a double dose to compensate for the missed doses.

If you interrupt the treatment with 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 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 associated with bosentan are:

• Abnormal liver function that may affect more than 1 in 10 people.
• Anemia (decreased blood count) that may 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 that these analyses are performed 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).
• Icterus (yellowish discoloration of the skin or white of the eyes).
• Dark-colored urine.
• Itching (pruritus).
• Lethargy or fatigue (unusual tiredness or exhaustion).
• Pseudogripal syndrome (joint and muscle pain with fever).

If you experience 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 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(may 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 possible exacerbation of hepatitis and/or icterus (yellowish discoloration of the skin or white of the eyes).

Rare(may 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 the 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 "CAD.:". The expiration date is the last day of the month indicated.

This medication does not require special conditions for conservation.

Medications should not be disposed of through drains or in the trash. Dispose of packaging and medications you no longer need at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition of Bosentan Normon 125 mg film-coated tablets

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

• The other components are: maize pregelatinized starch, sodium carboxymethyl starch type A, anhydrous colloidal 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 contents of the packaging

Bosentan Normon 125 mg are film-coated, elongated, biconvex, orange-white tablets.

Bosentan Normon 125 mg film-coated tablets are available in blisters of Aluminio/Aluminio-poliamida-PVC or Aluminio/PVDC-PE, containing 14, 56, or 112 tablets.

Only some package sizes may be commercially available.

Holder of the marketing authorization and responsible manufacturer

LABORATORIOS NORMON, S.A.

C/ Ronda de Valdecarrizo, 6

28760 Tres Cantos, Madrid

Spain

This medicinal product is authorized in the member states of the European Economic Area with the following names:

Portugal: Bosentano Normon 125 mg film-coated tablets

Last review date of this leaflet: June 2021

Detailed and updated 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/