Bopaho

Package leaflet: Information for the patient

Bopaho, 125 mg, film-coated tablets
Bozentan
Please read this leaflet carefully before taking this medicine, as it contains important information for you.

• 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 pass it on to others. This medicine may harm other people, even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, please inform your doctor or pharmacist. See section 4.

Table of contents

1. What Bopaho is and what it is used for
2. Important information before taking Bopaho
3. How to take Bopaho
4. Possible side effects
5. How to store Bopaho
6. Contents of the pack and other information

1. What Bopaho is and what it is used for

Bopaho tablets contain bosentan, which blocks a naturally occurring hormone called endothelin-1 (ET-1) that causes narrowing of blood vessels. Therefore, Bopaho causes blood vessels to widen; it belongs to a group of medicines known as "endothelin receptor antagonists". Bopaho is used to treat:

• Pulmonary arterial hypertension (PAH). PAH is a disease characterized by severe narrowing of the blood vessels in the lungs, leading to high blood pressure in the pulmonary arteries (the blood vessels carrying 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. Bopaho widens the pulmonary arteries, allowing the heart to pump blood more easily. As a result, blood pressure is reduced and symptoms improve.

Bopaho is used in the treatment of patients with PAH in WHO functional class III to improve exercise capacity (ability to perform physical activity) and to relieve symptoms. The "class" reflects the severity of the disease. "Class III" means there is a marked limitation in physical activity. Some improvement has also been demonstrated in patients with PAH in functional class II. "Class II" means there is a slight limitation in physical activity. The types of PAH for which Bopaho is indicated include:

• Idiopathic (without identified cause) or hereditary PAH.
• PAH associated with systemic sclerosis (also known as scleroderma, a disease in which there is abnormal growth of connective tissue supporting the skin and other organs).
• PAH associated with congenital heart defects involving shunts (abnormal connections) causing abnormal blood flow through the heart and lungs.

Bopaho is also used to treat:

• Digital ulcers (sores on the fingertips and toes) in adult patients with systemic sclerosis. Bopaho reduces the number of new digital ulcers that develop on the fingers and toes.

2. Important information before taking Bopaho

When not to take Bopaho:

• if the patient is allergic to bosentan or any of the other ingredients of this medicine (listed in section 6),
• if the patient has liver problems (consult the treating physician),
• if the patient is pregnant or may become pregnant and is not using effective contraceptive methods; please refer to the information provided under the sections "Contraceptive methods" and "Other medicines and Bopaho",
• if the patient is taking cyclosporine A (a medicine used after organ transplantation or in the treatment of psoriasis). If any of the above situations apply, the patient must inform the treating physician.

Warnings and precautions
The doctor will order the following tests before starting treatment:

• blood test to check liver function,
• blood test to rule out anemia (low hemoglobin levels),
• pregnancy test in women of childbearing age.
  Some patients taking Bopaho have shown abnormal liver function test results and anemia (low hemoglobin levels).

Tests the doctor will perform during treatment
While being treated with Bopaho, the treating physician will regularly order blood tests to monitor changes in liver function and hemoglobin levels.
A description of all required tests is also included in the Patient Alert Card (located inside the Bopaho packaging). It is important to have blood tests performed regularly during treatment with Bopaho.
It is recommended that the patient record the date of the last and next blood test (according to the schedule set by the treating physician) on the Patient Alert Card to avoid missing appointments.

Blood tests to monitor liver function
During Bopaho treatment, these tests will be performed monthly. After any dose increase, an additional test should be performed after 2 weeks.

Blood tests to rule out anemia
These tests will be performed monthly for the first 4 months of treatment, and then every 3 months, as anemia may occur in patients taking Bopaho.
If test results are abnormal, the treating physician may decide to reduce the dose or discontinue treatment with Bopaho and perform additional tests to determine the cause.

Children and adolescents
Bopaho is not recommended for children and adolescents with systemic sclerosis and digital ulcers. See also section 3, "How to take Bopaho".

Other medicines and Bopaho
Inform your doctor or pharmacist about all medicines you are currently taking or have recently taken, including those obtained without a prescription, as well as any medicines you plan to take. In particular, 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 Bopaho.
• Sirolimus or tacrolimus, medicines used after transplantation, as they are not recommended to be used together with Bopaho.
• Glibenclamide (a medicine for diabetes), rifampicin (an anti-tuberculosis medicine), fluconazole (an antifungal medicine), ketoconazole (a medicine used in the treatment of Cushing's syndrome), or nevirapine (an anti-HIV medicine), as these medicines are not recommended to be used together with Bopaho.
• Other medicines for HIV infection, which may require special monitoring if used together with Bopaho.
• Hormonal contraceptives, which are not effective as the sole method of contraception during treatment with Bopaho. The Patient Alert Card included inside the Bopaho tablet packaging should be carefully read. The treating physician and/or gynecologist will determine the most appropriate contraceptive method for the patient.
• Other medicines used to treat pulmonary hypertension: sildenafil and tadalafil.
• Warfarin (an anticoagulant medicine).
• Simvastatin (a medicine used to treat hypercholesterolemia).

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult her doctor or pharmacist before taking Bopaho.

Women of childbearing potential
Bopaho must NOT be taken by patients who are pregnant or who plan to become pregnant.

Pregnancy tests
Bopaho may be harmful to fetuses conceived before or during treatment. If the patient may become pregnant, the doctor will request a pregnancy test before starting Bopaho and regular tests during treatment.

Contraceptive methods
If the patient may become pregnant, she must use an effective method of contraception during treatment with Bopaho. The treating physician or gynecologist will advise on the use of effective contraceptive methods during Bopaho treatment. Since Bopaho may reduce the effectiveness of hormonal contraceptives (e.g., oral, injectable, implants, or transdermal patches), hormonal contraception alone cannot be relied upon. Therefore, when using hormonal contraceptives, a barrier method must also be used (e.g., female condom, diaphragm, contraceptive sponge, or the patient's partner must use a male condom).

The Patient Alert Card inside the Bopaho tablet packaging should be completed and brought to the next medical visit so that the treating physician or gynecologist can assess whether additional or alternative effective contraceptive methods are needed. Monthly pregnancy tests are recommended for women of childbearing age during Bopaho treatment.

The patient must immediately inform her doctor if she becomes pregnant while taking Bopaho or if she plans a pregnancy in the near future.

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

Fertility
In male patients taking Bopaho, the medicine may reduce sperm count in semen. It cannot be ruled out that this may affect the ability to father a child. If the patient has any questions or concerns about this, he should consult his doctor.

Driving and using machines
Bopaho has no or negligible influence on the ability to drive or operate machinery. However, Bopaho may cause hypotension (low blood pressure), which may lead to dizziness, visual disturbances, and affect the ability to drive or operate machinery. Therefore, if dizziness or blurred vision occurs during treatment with Bopaho, the patient must not drive, use tools, or operate machinery.

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

3. How to use Bopaho

Treatment with Bopaho should be initiated and supervised by a physician experienced in the treatment of PAH or systemic sclerosis. This medicine should always be used exactly as prescribed by your doctor. If in doubt, consult your doctor or pharmacist.

Recommended dose
Adults
Treatment in adult patients usually starts with a dose of 62.5 mg twice daily (in the morning and in the evening) for the first 4 weeks. Afterwards, your doctor will usually recommend increasing to one 125 mg tablet twice daily, depending on the patient's response to Bopaho. The medicinal product Bopaho 62.5 mg is not available.

Use in children and adolescents
The recommended dosing for children applies only to the treatment of PAH. In children aged 1 year and older, bosentan treatment usually starts at a dose of 2 mg per kg body weight twice daily (in the morning and in the evening). The prescribing physician determines the exact dose.

If you feel that the effect of Bopaho is too strong or too weak, consult your doctor for possible dose adjustment.

How to use Bopaho
Take the tablets twice daily (in the morning and in the evening) with water. The tablets may be taken with or without food.

Taking more Bopaho than recommended
If you take more tablets than prescribed, contact your doctor immediately.

Missing a dose of Bopaho
If you miss a dose of Bopaho, take it as soon as you remember, then continue taking the tablets at your usual times. Do not take a double dose to make up for a missed dose.

Stopping Bopaho
Stopping treatment with Bopaho suddenly may lead to worsening of symptoms. Do not discontinue Bopaho unless instructed by your doctor. Your doctor may advise you to gradually reduce the dose over several days before completely stopping the medicine.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine may cause adverse effects, although not everyone will experience them.
The most serious adverse effects of Bopaho are:

• Impaired liver function, which may occur in more than 1 in 10 patients.
• Anaemia (low number of blood cells), which may occur in up to 1 in 10 patients. Blood transfusion may sometimes be necessary in cases of anaemia.

Liver function tests and blood counts will be monitored during treatment with Bopaho (see section 2). It is important that the patient undergoes these tests as recommended by the doctor.
Symptoms of impaired liver function include:

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

If the patient notices any of these symptoms, they should inform their doctor immediately.
Other adverse effects
Very common (may affect more than 1 in 10 patients):

• Headache
• Oedema (swelling of legs and ankles or other signs of fluid retention)

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

• Sudden hot flushes or skin redness
• Hypersensitivity reactions (including skin inflammation, itching and rash)
• Gastro-oesophageal reflux disease (reflux of stomach acid)
• Diarrhoea
• Loss of consciousness (fainting)
• Palpitations (fast or irregular heartbeat)
• Low blood pressure
• Nasal congestion

Uncommon (may affect up to 1 in 100 patients):

• Thrombocytopenia (low platelet count)
• Neutropenia/leukopenia (low white blood cell count)
• Elevated liver function test results associated with hepatitis, including possible worsening of existing hepatitis and (or) jaundice (yellowing of the skin or whites of the eyes)

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

• Anaphylaxis (generalised allergic reaction), angioedema (swelling most commonly affecting the eyes, lips, tongue or throat)
• Liver cirrhosis (liver fibrosis), liver failure (severe liver function impairment), autoimmune hepatitis (liver inflammation caused by the body's immune cells attacking liver cells), which may occur even several months to several years after starting treatment.

Blurred vision has also been reported with unknown frequency (frequency cannot be estimated from available data).
Adverse effects in children and adolescents
Adverse effects observed in children treated with Bopaho are the same as in adults.
Reporting of adverse effects
If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department for Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, Poland.
Tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the Marketing Authorisation Holder or its representative in Poland.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Bopaho medicine

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the cardboard box. The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. Such measures help protect the environment.

6. Contents of the pack and other information

What Bopaho contains
The active substance is bosentan.
Each tablet contains 125 mg of bosentan (in the form of monohydrate).
The other ingredients are: maize starch, povidone (K-30), sodium carboxymethyl starch, type A;
pregelatinized maize starch; glycerol dibehenate, magnesium stearate, Opadry II 85F230061 orange
[a mixture containing polyvinyl alcohol, titanium dioxide (E 171), macrogol 3350, talc, iron oxide yellow (E172) and iron oxide red (E172)].

What Bopaho looks like and contents of the pack
Bopaho 125 mg: oval, biconvex, light orange film-coated tablets, approximately 11.1 mm in length and 5.1 mm in width.
Pack sizes: 14, 56 or 112 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Zentiva, k.s., U kabelovny 130, Dolní Měcholupy, 102 37 Prague 10, Czech Republic

Importer
Zentiva, k.s., U kabelovny 130, Dolní Měcholupy, 102 37 Prague 10, Czech Republic
S.C. Zentiva, S.A, B-dul Theodor Pallady nr.50, sector 3, 032266 Bucharest, Romania
ITC Production S.r.l., Via Pontina KM 29, 00071 Pomezia (Rome), Italy

This medicinal product is authorised in the European Economic Area countries under the following names:
Poland and Romania: Bopaho

For further information about this medicinal product and its names in the European Economic Area countries, please contact the representative of the Marketing Authorisation Holder in Poland:
Zentiva Polska Sp. z o.o.
ul. Bonifraterska 17
00-203 Warsaw
Tel. (22) 375 92 00