Package leaflet: Information for the patient

Bosentan Sandoz GmbH, 125 mg, film-coated tablets
Bosentanum
Please read carefully the entire leaflet before taking the medicine, as it contains
important information for the patient.
Keep this leaflet, as you may need to read it again.
If you have any further questions, please consult your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not give it to others.
The medicine may harm another person, even if their symptoms are the same.
If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of the leaflet

What Bosentan Sandoz GmbH is and what it is used for
Important information before taking Bosentan Sandoz GmbH
How to take Bosentan Sandoz GmbH
Possible side effects
How to store Bosentan Sandoz GmbH
Contents of the package and other information

1. What Bosentan Sandoz GmbH is and what it is used for

Bosentan Sandoz GmbH contains bosentan, which blocks a naturally occurring hormone called endothelin-1 (ET-1) that causes narrowing of blood vessels. Therefore, Bosentan Sandoz GmbH causes blood vessels to dilate and belongs to a group of medicines known as "endothelin receptor antagonists".
Bosentan Sandoz GmbH is used to treat:

pulmonary arterial hypertension (PAH). PAH is a disease characterized by significant narrowing of blood vessels in the lungs, leading to high blood pressure in the blood vessels (pulmonary arteries) that carry blood from the heart to the lungs. This high pressure reduces the amount of oxygen that can enter the blood in the lungs, making physical activity difficult. Bosentan Sandoz GmbH dilates the pulmonary arteries, making it easier for the heart to pump blood. As a result, blood pressure is reduced and symptoms improve.

Bosentan Sandoz GmbH is used in the treatment of patients with pulmonary arterial hypertension (PAH) in WHO functional class III to improve exercise capacity (ability to perform physical activity) and relieve symptoms. The "class" reflects the severity of the disease: class III is associated with marked limitation of physical activity. Some improvement has also been demonstrated in patients with PAH in class II. Class II is associated with slight limitation of physical activity.
PAH treated with Bosentan Sandoz GmbH may be:

idiopathic (without identified cause) or hereditary;
caused by scleroderma (also called systemic sclerosis – a disease in which there is abnormal growth of connective tissue supporting the skin and other organs);
caused by congenital heart defects associated with shunts (abnormal blood flow) through the heart and lungs.

digital ulcers on fingertips (sores on fingers and toes) in adult patients with a disease called systemic sclerosis. Bosentan Sandoz GmbH reduces the number of new digital ulcers appearing on the fingertips and toes.

2. Important information before using Bosentan Sandoz GmbH

When not to use Bosentan Sandoz GmbH
if the patient has hypersensitivity to bosentan or to any of the other ingredients of this medicine
(listed in section 6);
if the patient has liver function abnormalities (consult a doctor in this regard);
if the patient is pregnant or may become pregnant and is not using an effective method of
contraception (please read the information under "Contraception" and "Bosentan Sandoz GmbH and
other medicines");
if the patient is receiving cyclosporine A (a medicine used after transplantation or in the treatment
of psoriasis).
If any of the above situations apply to the patient, inform the doctor.

Warnings and precautions
Before taking Bosentan Sandoz GmbH, discuss it with your doctor or pharmacist.

Tests your doctor will perform before starting treatment
a blood test to assess liver function
a blood test to rule out anaemia (low haemoglobin levels)
a pregnancy test in women of childbearing potential

Some patients taking Bosentan Sandoz GmbH may develop abnormal liver function test results and anaemia (low haemoglobin levels).

Tests your doctor will perform during treatment
During treatment with Bosentan Sandoz GmbH, your doctor will order regular blood tests to monitor changes in liver function and haemoglobin levels.
Details of all these tests are also provided in the Warning Card (included in the medicine package).
It is important that the patient undergoes regular blood tests while taking Bosentan Sandoz GmbH. The date of the last and next scheduled blood test (according to the doctor's instructions) should be recorded in the Warning Card.

Blood tests to assess liver function
These tests are performed once a month throughout the entire duration of Bosentan Sandoz GmbH treatment. After an increase in dose, an additional test should be performed after 2 weeks.

Blood tests to rule out anaemia
These tests are performed once a month during the first 4 months of treatment, then every 3 months, as anaemia may occur in patients taking Bosentan Sandoz GmbH.
If test results are abnormal, the doctor may decide to reduce the dose or discontinue Bosentan Sandoz GmbH and perform additional tests to determine the cause of anaemia.

Children and adolescents
Bosentan Sandoz GmbH is not recommended for use in children and adolescents with systemic sclerosis and digital ulcers. Bosentan Sandoz GmbH should also not be used in children with pulmonary arterial hypertension who weigh less than 31 kg. See also section 3 "How to take Bosentan Sandoz GmbH".

Bosentan Sandoz GmbH and other medicines
Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take, including those available without a prescription. It is especially important to inform your doctor if you are taking:
cyclosporine A (a medicine used after transplantation or in the treatment of psoriasis), which must not be used together with Bosentan Sandoz GmbH;
sirolimus or tacrolimus (medicines used after transplantation), as their use together with Bosentan Sandoz GmbH is not recommended;
glibenclamide (a medicine used to treat diabetes), rifampicin (a medicine used to treat tuberculosis), fluconazole (a medicine used to treat fungal infections), ketoconazole (a medicine used to treat Cushing's syndrome), or nevirapine (a medicine used to treat HIV infections), as their use together with Bosentan Sandoz GmbH is not recommended;
other medicines used to treat HIV infections, as concomitant use with Bosentan Sandoz GmbH may require special monitoring;
hormonal contraceptives, as they are ineffective as the sole method of contraception during treatment with Bosentan Sandoz GmbH. Please carefully read the content of the Warning Card included in the medicine package. Your treating doctor and/or gynaecologist will advise you on the most appropriate contraceptive method;
other medicines used to treat pulmonary hypertension: sildenafil and tadalafil;
warfarin (an anticoagulant medicine);
simvastatins (a medicine used to treat hypercholesterolaemia).

Pregnancy, breastfeeding and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.

Women of childbearing potential
Bosentan Sandoz GmbH MUST NOT be used in women who are pregnant or planning to become pregnant.

Pregnancy tests
Bosentan Sandoz GmbH may harm the unborn child conceived before or during treatment. If the patient may become pregnant, the doctor will recommend a pregnancy test before starting Bosentan Sandoz GmbH and regular repeat testing during treatment.

Contraception
If the patient may become pregnant, she should use an effective method of birth control during treatment with Bosentan Sandoz GmbH. Your treating doctor or gynaecologist will advise you on using effective contraception while taking Bosentan Sandoz GmbH. Since this medicine may reduce the effectiveness of hormonal contraceptives (e.g. oral, injectable, implants, or skin patches), using this method alone will not be effective. Therefore, patients using hormonal contraceptives should also use a barrier method (such as a female condom, diaphragm, contraceptive sponge) or the patient's partner should use a male condom. The Warning Card included in the medicine package should be completed and brought to the next doctor's visit so that the treating doctor or gynaecologist can assess whether additional or alternative effective contraceptive methods are needed. It is recommended that women of childbearing potential perform a monthly pregnancy test during treatment with Bosentan Sandoz GmbH.
Inform your doctor immediately if you become pregnant while taking Bosentan Sandoz GmbH or if you plan to become pregnant in the near future.

Breastfeeding
Bosentan Sandoz GmbH passes into human milk. Breastfeeding should be discontinued if Bosentan Sandoz GmbH is prescribed, as it is unknown whether Bosentan Sandoz GmbH present in breast milk may harm the infant. Discuss this with your doctor.

Fertility
If a man takes Bosentan Sandoz GmbH, the medicine may reduce the number of sperm in semen. It cannot be excluded that this may affect the ability to father a child. If the patient has any questions or concerns regarding this issue, he should consult his doctor.

Driving and operating machinery
Bosentan Sandoz GmbH has no effect or has a negligible effect on the ability to drive and operate machinery. However, Bosentan Sandoz GmbH may cause hypotension (lowering of blood pressure), which may lead to dizziness, blurred vision, and affect the ability to drive and operate machinery. Therefore, if dizziness or blurred vision occurs while taking Bosentan Sandoz GmbH, the patient should not drive or operate tools or machinery.

Bosentan Sandoz GmbH contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per coated tablet, meaning the medicine is considered "sodium-free".

3. How to use Bosentan Sandoz GmbH

This medicine should always be used as directed by your doctor or pharmacist. If in doubt,
consult your doctor or pharmacist.
Treatment with Bosentan Sandoz GmbH should only be initiated and monitored by a physician
experienced in the treatment of pulmonary arterial hypertension or systemic sclerosis.
Recommended dose
Adults
In adult patients, treatment is usually started at 62.5 mg of bosentan twice daily (in the morning
and evening) for 4 weeks, after which the doctor will usually recommend increasing to one 125 mg tablet twice daily, depending on the patient's response to bosentan.
Use in children and adolescents
Dosing recommendations in children apply only to pulmonary arterial hypertension. In children from the age of 1 year, treatment with Bosentan Sandoz GmbH usually starts at 2 mg per kg of body weight given twice daily (in the morning and evening). However, administering certain doses of bosentan to children weighing less than 31 kg is not feasible. In such cases, bosentan in lower-strength tablets should be used. Your doctor will advise on the appropriate dosing.
Bosentan is also available in dispersible tablets of 32 mg strength, which facilitates accurate dosing in children and patients with low body weight or difficulty swallowing coated tablets.
If the patient feels that the effect of Bosentan Sandoz GmbH is too strong or too weak, consult the doctor to determine whether the dose being taken should be adjusted.
How to take Bosentan Sandoz GmbH
The tablets should be taken in the morning and evening, with water. The tablets may be taken with or without food.
If you take more Bosentan Sandoz GmbH than you should
If you take more tablets than recommended, contact your doctor immediately.
If you forget to take Bosentan Sandoz GmbH
If the patient forgets to take a dose of Bosentan Sandoz GmbH, the missed dose should be taken as soon as remembered, and then continue taking the tablets at the usual times. Do not take a double dose to make up for a missed dose.
Stopping Bosentan Sandoz GmbH
Suddenly stopping treatment with Bosentan Sandoz GmbH may worsen symptoms. Do not stop taking this medicine without consulting your doctor. The doctor may advise gradually reducing the dose over several days before completely discontinuing the medicine.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although they do not occur in everyone.
The most serious adverse reactions with Bosentan Sandoz GmbH are:

liver function abnormalities, which may occur in more than 1 in 10 people,
anaemia (low number of red blood cells), which may occur in less than 1 in 10 people. Anaemia may occasionally require blood transfusion.

While taking Bosentan Sandoz GmbH, your doctor will monitor your liver function tests and blood counts (see section 2). It is important to have these tests performed as recommended by your doctor.
Symptoms of abnormal liver function include:

nausea (feeling sick),
vomiting,
fever (high temperature),
stomach (abdominal) pain,
jaundice (yellowing of the skin or whites of the eyes),
dark urine,
skin itching,
lethargy or fatigue (unusual tiredness or exhaustion),
flu-like symptoms (joint and muscle pain with fever).

If you notice any of these symptoms, seek medical advice immediately.
Other adverse reactions
Very common (may affect more than 1 in 10 people)
headache
swelling (of legs and ankles or other signs of fluid retention)
Common (may affect less than 1 in 10 people)
skin redness, including face
hypersensitivity reactions (including skin inflammation, itching and rash)
gastro-oesophageal reflux disease (backflow of stomach acid into the oesophagus)
diarrhoea
fainting
palpitations (fast or irregular heartbeat)
low blood pressure
nasal congestion (nasal mucosal hyperaemia)
Uncommon (may affect less than 1 in 100 people)
thrombocytopenia (low platelet count)
neutropenia and (or) leukopenia (low white blood cell count)
increased liver function test values (liver inflammation, including possible worsening of pre-existing liver disease) and (or) jaundice (yellowing of the skin and whites of the eyes)
Rare (may affect less than 1 in 1000 people)
anaphylactic reaction (generalised allergic reaction), angioedema (swelling, usually around the eyes, lips, tongue or throat)
liver cirrhosis, liver failure (severe liver dysfunction), autoimmune hepatitis (liver inflammation caused by the body's immune cells attacking liver cells), which may occur several months to several years after starting treatment
Cases of blurred vision have also been reported with unknown frequency (frequency cannot be estimated from available data).
Adverse reactions in children and adolescents
Adverse reactions observed in children and adolescents are the same as those in adults.
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department for Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warsaw
tel.: + 48 22 49 21 301/fax: + 48 22 49 21 309/website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Bosentan Sandoz GmbH

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the cardboard box and blister pack following EXP. The expiry date refers to the last day of the specified month.
The batch number on the packaging is marked as "Lot".
No special storage conditions are required.
Medicines should not be disposed of via wastewater or household waste. 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

What Bosentan Sandoz GmbH contains
The active substance is bosentan (monohydrate).
Each coated tablet contains 125 mg of bosentan in the form of bosentan monohydrate (129.082 mg).
The other ingredients are: maize starch, pregelatinized maize starch, sodium carboxymethyl starch (type A), povidone K30, poloxamer 188, colloidal anhydrous silica, glyceryl dibehenate, magnesium stearate.
Coating (Opadry Orange 21K23007): hypromellose 2910, titanium dioxide (E 171), ethylcellulose, triacetin (E 1518), talc (E 553b), yellow iron oxide (E 172), red iron oxide (E 172), black iron oxide (E 172).

What Bosentan Sandoz GmbH looks like and contents of the pack
Light orange, oval, biconvex tablets measuring 11 x 5 mm.
The coated tablets are packed in blisters made of PVC/PVDC/Aluminium foil and placed in a cardboard box.
Pack sizes:
14, 56 or 112 coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Sandoz GmbH
Biochemiestrasse 10
6250 Kundl, Austria

Manufacturer/Importer
Lek Pharmaceuticals d.d.
Verovškova ulica 57
1526 Ljubljana, Slovenia
Salutas Pharma GmbH
Otto-von-Guericke-Allee 1
39179 Barleben, Germany

For further information about this medicinal product and its names in the Member States of the European Economic Area, please contact:
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
02-672 Warszawa
tel. 22 209 70 00