BOSENTAN KERN PHARMA 62.5 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Bosentan Kern Pharma 62.5 mg film-coated tablets EFG

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

1. What is Bosentan Kern Pharma and what is it used for

Bosentan Kern Pharma contains bosentan, which blocks a natural hormone called endothelin-1 (ET-1), causing narrowing of blood vessels. Bosentan, therefore, causes dilation of blood vessels. It 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 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. '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 (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 Kern Pharma

Do not take Bosentan Kern Pharma

• 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 become pregnant by not using reliable contraceptive methods. Please read the information in the section "Contraceptives" and "Other medicines and Bosentan Kern Pharma"
• 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

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

Abnormalities in 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 tablets). It is essential that you have regular blood tests while taking this medicine. 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 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. See also section 3. How to take Bosentan Kern Pharma.

Other medicines and Bosentan Kern Pharma

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), which 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, and ketoconazole (medicines for fungal infections), 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, when administered with bosentan, may require special monitoring.
• oral contraceptives, which are not effective as the only contraceptive method when taking bosentan. Inside the package of this medicine, you will find a Patient Alert Card that you must 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 hypercholesterolemia).

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, or 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 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 this medicine.

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 this medicine. Since bosentan can make hormonal contraception 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, contraceptive sponge, or your partner must also use a condom). Inside the package of this medicine, 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 doctor immediatelyif 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, this medicine 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 Kern Pharma 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 Kern Pharma

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

Use of Bosentan Kern Pharma with food and drinks

This medicine 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 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.

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.

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

How to take Bosentan Kern Pharma

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

If you take more Bosentan Kern Pharma than you should

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

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

If you forget to take Bosentan Kern Pharma

If you forget to take this medicine, 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 Kern Pharma

If you suddenly stop taking this medicine, 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, pharmacist, or nurse.

4. Possible side effects

Like all medicines, Bosentan Kern Pharma 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 value) that can affect more than 1 in 10 people. Anemia may occasionally require blood transfusion.

Your liver and blood values will be analyzed 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 correctly include:

• nausea (need to vomit)
• vomiting
• fever (high temperature)
• stomach pain (abdomen)
• jaundice (yellow color of skin or whites 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 10 people):

• headache
• edema (swelling of the legs and ankles or other signs of fluid retention)

Common(may affect up to 1 in 10 people):

• 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 100 people):

• thrombocytopenia (decrease in platelet count in blood)
• neutropenia/leucopenia (decrease in white blood cell count in blood)
• elevated liver function tests with hepatitis (inflammation of the liver) including possible exacerbation of underlying hepatitis and/or jaundice

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

• 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)

Side effects in children and adolescents

The side effects that have been observed in children treated with bosentan are the same as in adults.

Blurred vision has also been reported with an unknown frequency (cannot be estimated from the available data).

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: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Bosentan Kern Pharma

Keep this medicine out of the sight and reach of children.

No special storage conditions are required.

Do not use this medicine after the expiry date which is stated on the packaging after "EXP". The expiry date is the last day of the month indicated.

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

6. Contents of the pack and other information

Composition of Bosentan Kern Pharma

• Bosentan Kern Pharma 62.5 mg:The active ingredient is bosentan. Each tablet contains 62.5 mg of bosentan (as monohydrate).

• Bosentan Kern Pharma 125 mg: The active ingredient is bosentan. Each tablet contains 125 mg of bosentan (as monohydrate).
• The other ingredients are pregelatinized corn starch, povidone, sodium carboxymethylcellulose type A (from potato), magnesium stearate, and opadry orange 03K93638 (a mixture consisting of hydroxypropyl methylcellulose, red iron oxide (E-172), yellow iron oxide (E-172), titanium dioxide (E-171), and triacetin).

Appearance of the product and contents of the pack

Bosentan Kern Pharma 62.5 mg: round, orange-white, film-coated tablets.

PVC/PCTFE/Aluminum blisters containing 56 tablets.

Bosentan Kern Pharma 125 mg: oval, orange-white, film-coated tablets.

PVC/PCTFE/Aluminum blisters containing 56 tablets.

Marketing authorization holder and manufacturer

Kern Pharma, S.L.

Venus, 72 - Pol. Ind. Colón II

08228 Terrassa - Barcelona

Spain

Date of last revision of this leaflet:May 2024

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