Bopaho

Package leaflet: Information for the patient

Bopaho, 125 mg, film-coated tablets

• Bosentan *
  Please read carefully all the information in this 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 doubts, please consult your doctor or pharmacist.

• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm someone else, even if their symptoms are the same.

• If you experience any adverse reactions, including any not listed in this leaflet, tell 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 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. Bopaho widens the pulmonary arteries, allowing the heart to pump blood more easily. As a result, blood pressure is lowered and symptoms improve.

Bopaho is used in the treatment of PAH patients 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" means a marked limitation in physical activity. Improvement has also been demonstrated in patients in WHO functional class II. "Class II" means a slight limitation in physical activity. The types of PAH for which Bopaho is indicated include:

• Idiopathic (without identified cause) or heritable PAH.
• PAH associated with scleroderma (also known as systemic sclerosis, a disease characterized by 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 indicated for the treatment of:

• 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 because effective contraception is not being used; please read the information provided under the sections "Contraceptive methods" and "Bopaho with other medicines",
• 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 should inform their doctor.

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 tests is also included in the Patient Alert Card (inside the Bopaho packaging). It is important to have blood tests performed regularly while taking 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 an appointment.

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, 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 use in children and adolescents with systemic sclerosis and digital ulcers. See also section 3. "How to take Bopaho".

Bopaho with other medicines
Inform your doctor or pharmacist about any medicines you are currently taking, have recently taken, or plan to take, including those obtained without a prescription. 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 for use 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 for use together with Bopaho.
• Other medicines for the treatment of 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. Inside the Bopaho tablet packaging, there is a Patient Alert Card that 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 is planning to have a child, she should consult her doctor or pharmacist before taking Bopaho.

Women of childbearing potential
Bopaho must NOT be taken by a woman who is pregnant or planning 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 testing 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. Because Bopaho may reduce the effectiveness of hormonal contraceptives (e.g. oral, injectable, implants, or transdermal patches), hormonal contraception alone cannot be relied upon. For this reason, 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).

Inside the Bopaho tablet packaging, there is a Patient Alert Card. It should be completed and brought to the next appointment 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 is not recommended during treatment with Bopaho, 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 excluded that this may affect the ability to father a child. If the patient has any questions or concerns about this issue, he should consult his doctor.

Driving and operating machinery
Bopaho has no or negligible influence on the ability to drive and operate machinery.
However, Bopaho may cause hypotension (low blood pressure), which may lead to dizziness, affect vision, and impair the ability to drive or operate machinery. Therefore, if dizziness or blurred vision occurs while taking 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 recommended by your doctor.
If you have any doubts, consult your doctor or pharmacist.
Recommended dose
Adults
Treatment in adult patients is usually started at a dose of 62.5 mg twice daily (morning and evening) for the first 4 weeks. Then, depending on the patient's response to Bopaho, the doctor will usually recommend increasing to a dose of 125 mg twice daily. The medicinal product Bopaho 62.5 mg is not available.
Use in children and adolescents
The recommended dosing in children applies only to the treatment of PAH. In children aged 1 year and older, treatment with bosentan is usually initiated at a dose of 2 mg per kg body weight twice daily (morning and evening). The prescribing physician determines the appropriate 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
Tablets should be taken twice daily (morning and evening), with water. The tablets may be taken with or without food.
Taking more Bopaho than recommended
If you take more tablets than recommended, 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
Abruptly stopping treatment with Bopaho may lead to worsening of symptoms. Do not stop taking Bopaho unless instructed by your doctor. Your doctor may advise you to gradually reduce the dose over several days before completely stopping the medication.
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 not everybody will get them.
The most serious adverse reactions with 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,
• vomiting,
• fever (high temperature),
• abdominal pain (stomach pain),
• jaundice (yellowing of the skin or whites of the eyes),
• dark 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 reactions
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 (backflow 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 number of platelets)
• Neutropenia/leukopenia (low number of white blood cells)
• Increased 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 impairment of liver function).

Blurred vision has also been reported with unknown frequency (frequency cannot be determined from available data).
Adverse reactions in children and adolescents
Adverse reactions observed in children treated with Bopaho are the same as in adults.
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, tell your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions at the 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 reactions can also be reported to the marketing authorisation holder or its representative in Poland.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Bopaho medicine

Keep the 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 required. 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 (as monohydrate).
The other ingredients are: maize starch, povidone (K-30), sodium carboxymethyl starch, type A;
pregelatinized corn 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 more detailed information about the 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