Bopaho

Leaflet accompanying the packaging: patient information

Bopaho, 62.5 mg, film-coated tablets

Bopaho, 125 mg, film-coated tablets

Bosentan

Read the leaflet carefully before taking the medicine, as it contains important information for the patient.

• 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 a specific person. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including those not listed in this leaflet, they should inform their doctor or pharmacist. See section 4.

Table of contents of the leaflet

• 1. What is Bopaho and what is it 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 is Bopaho and what is it used for

Bopaho tablets contain bosentan, which blocks a naturally occurring hormone called endothelin-1 (ET-1), causing blood vessels to constrict. As a result, Bopaho causes blood vessels to dilate; this medicine belongs to a group of medicines called "endothelin receptor antagonists".

Bopaho is used to treat:

• Pulmonary arterial hypertension (PAH). PAH is a disease characterized by severe constriction of blood vessels in the lungs, leading to high blood pressure in the blood vessels of the lungs (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 dilates the pulmonary arteries, making it easier for the heart to pump blood. As a result, blood pressure decreases and symptoms improve.

Bopaho is used to treat patients with PAH class III to improve exercise capacity (ability to perform physical exercise) and alleviate symptoms. The "class" reflects the severity of the disease. "Class III" is associated with significant limitation of physical activity. Some improvement has also been shown in patients with PAH class II. "Class II" is associated with mild limitation of physical activity. PAH, for which Bopaho is indicated, may be:

• primary (without a known cause or familial).
• caused by scleroderma (also known as systemic sclerosis, a disease in which there is abnormal growth of connective tissue that supports the skin and other organs).
• caused by congenital heart defects associated with shunts (abnormal connections) that cause abnormal blood flow through the heart and lungs.

Bopaho is used to treat:

• digital ulcers(sores on fingers and toes) in adult patients with systemic scleroderma. Bopaho reduces the number of new digital ulcers on fingers and toes.

2. Important information before taking Bopaho

When not to take Bopaho:

• or any of the other ingredients of this medicine (listed in section 6),
• (should consult their doctor),
• , as they are not using effective contraception; should read the information in sections "Contraception" and "Bopaho and other medicines",
• (a medicine used after organ transplantation or in the treatment of psoriasis).

If any of the above applies to the patient, they 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 level),
• pregnancy test in women of childbearing age.

In some patients taking Bopaho, abnormal liver function test results and anemia (low hemoglobin level) have been observed.

Tests to be performed during treatment

During Bopaho treatment, the doctor will regularly order blood tests to monitor changes in liver function and hemoglobin levels.

Liver function tests

During Bopaho treatment, tests will be performed once a month. After a dose increase, an additional test should be performed after 2 weeks.

Blood tests to rule out anemia

Such tests will be performed once a month for the first 4 months of treatment, and then every 3 months, as anemia may occur in patients taking Bopaho.

Children and adolescents

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

Bopaho and other medicines

The patient should tell their doctor or pharmacist about all medicines they are taking, or have recently taken, including those obtained without a prescription, as well as any medicines they plan to take.

• Cyclosporin A (a medicine used after transplantation or in the treatment of psoriasis), which should not be taken at the same time as Bopaho.
• Sirolimus or tacrolimus, medicines used after transplants, which are not recommended to be taken at the same time as Bopaho.
• Glibenclamide (a medicine for diabetes), rifampicin (a medicine for tuberculosis), fluconazole (an antifungal medicine), ketoconazole (an antifungal medicine and used in the treatment of Cushing's syndrome), and nevirapine (a medicine for HIV), which are not recommended to be taken with Bopaho.
• Other medicines for the treatment of HIV infection, which may require special monitoring if taken at the same time as Bopaho.
• Hormonal contraceptives, which are not effective as the only method of contraception during Bopaho treatment. Inside the Bopaho tablet packaging, there is a Patient Alert Card, which should be read carefully. The doctor and/or gynecologist will determine the most suitable method of contraception for the patient.
• Warfarin (an anticoagulant medicine), which requires more frequent monitoring of the patient's condition when taken at the same time as Bopaho.
• Other medicines used to treat pulmonary hypertension: sildenafil and tadalafil.
• Simvastatin (a medicine used to treat high cholesterol), which may require monitoring of cholesterol levels and, if necessary, adjustment of the dose.

Driving and using machines

Bopaho has no or negligible influence on the ability to drive and use machines.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a baby, they should consult their doctor or pharmacist before taking Bopaho.

Women of childbearing age

Bopaho should not be taken by women who are pregnant or 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 ask for a pregnancy test before starting Bopaho treatment and regular tests during treatment.

Contraception

If the patient may become pregnant, they should use effective contraception during Bopaho treatment. The doctor and/or gynecologist will advise on the use of effective contraception during Bopaho treatment. Since Bopaho may cause hormonal contraceptives to be ineffective (e.g., oral, injections, implants, or transdermal patches), they should not be relied upon as the only method of contraception.

Breastfeeding

If the patient is breastfeeding, they should immediately inform their doctor.

After Bopaho has been prescribed, it is recommended to stop breastfeeding, as it is not known whether this medicine passes into human milk.

Fertility

If the male patient is taking Bopaho, it is possible that this medicine may reduce the number of sperm in the 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, they should consult their doctor.

Bopaho contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per tablet, which means it is essentially "sodium-free".

3. How to take Bopaho

Treatment with Bopaho should be started and supervised by a doctor with experience in the treatment of PAH or systemic scleroderma. This medicine should always be taken exactly as prescribed by the doctor.

Recommended dose

Adults

Treatment of adults usually starts with a dose of 62.5 mg twice a day (morning and evening) for the first 4 weeks, then the doctor usually recommends taking a 125 mg tablet twice a day, depending on the patient's response to Bopaho.

How to take Bopaho

Tablets should be taken twice a day (morning and evening), with water. Tablets can be taken with or without food.

Taking more Bopaho than recommended

In case of taking more tablets than recommended, the patient should immediately contact their doctor.

Missing a dose of Bopaho

In case of missing a dose, the patient should take it as soon as they remember, and then continue taking the tablets at the usual times. The patient should not take a double dose to make up for the missed dose.

Stopping Bopaho treatment

Sudden stopping of Bopaho treatment may lead to worsening of symptoms. The patient should not stop taking Bopaho unless their doctor tells them to. The doctor may recommend reducing the dose over a few days before completely stopping Bopaho treatment.

4. Possible side effects

Like all medicines, Bopaho can cause side effects, although not everybody gets them.

The most serious side effects of Bopaho are:

• Abnormal liver function (including severe cases), which may occur in more than 1 in 10 patients. Symptoms of abnormal liver function are:
• nausea (feeling sick),
• vomiting,
• fever (high temperature),
• abdominal pain (stomach pain),
• jaundice (yellowing of the skin or whites of the eyes),
• dark urine,
• itching of the skin,
• lethargy or fatigue (excessive tiredness or exhaustion),
• flu-like symptoms (muscle and joint pain and fever).
• Anemia (low red blood cell count), with symptoms such as pale skin and weakness or shortness of breath, which may occur in up to 1 in 10 patients. In anemia, blood transfusion may sometimes be necessary.
• Changes in blood cells (platelets and white blood cells) with symptoms of infection, unexplained bruising, or bleeding, which may occur in up to 1 in 1000 patients.
• Anaphylaxis (severe allergic reaction) causing difficulty breathing or dizziness, which may occur in up to 1 in 1000 patients.

If the patient notices any of these symptoms, they should immediately inform their doctor.

Other side effects:

Very common (may affect more than 1 in 10 patients):

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

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

• flushing (sudden warmth or redness of the skin)
• hypersensitivity reactions (including skin inflammation, itching, and rash)
• gastroesophageal reflux disease (stomach acid flowing back into the esophagus)
• diarrhea
• syncope (fainting)
• palpitations (fast or irregular heartbeat)
• low blood pressure
• nasal congestion

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

• elevated liver function test results associated with hepatitis, including possible exacerbation of existing hepatitis and/or jaundice (yellowing of the skin or whites of the eyes)

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

• angioedema (swelling that occurs most commonly around the eyes, lips, tongue, or throat)
• liver cirrhosis (scarring of the liver)

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

Side effects in children and adolescents

The side effects observed in children treated with Bopaho are the same as those in adults.

Reporting side effects

If the patient experiences any side effects, including those not listed in this leaflet, they should inform their doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw.

5. How to store Bopaho

The medicine should be stored out of sight and reach of children.

Do not use this medicine after the expiry date stated on the carton. The expiry date refers to the last day of the month.

Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines they no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Bopaho contains

The active substance is bosentan.

Bopaho, 62.5 mg: each tablet contains 62.5 mg of bosentan (as monohydrate).

Bopaho, 125 mg: each tablet contains 125 mg of bosentan (as monohydrate).

The other ingredients are: cornstarch, povidone (K-30), sodium carboxymethyl starch, type A; maize starch, pregelatinized; glycerol dibehenate, magnesium stearate, opadry II 85F230061 orange [a mixture containing polyvinyl alcohol, titanium dioxide (E 171), macrogol 3350, talc, yellow iron oxide (E172), and red iron oxide (E172)].

What Bopaho looks like and contents of the pack

Bopaho, 62.5 mg: round, biconvex, light orange film-coated tablets, approximately 6.1 mm in diameter.

Bopaho, 125 mg: oval, biconvex, light orange film-coated tablets, approximately 11.1 mm in length and 5.1 mm in width.

Package sizes: 56 or 112 film-coated tablets.

Not all package sizes may be marketed.

Marketing authorization 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

For more information on this medicine and its authorized names in the European Economic Area, please contact the representative of the marketing authorization holder in Poland:

Zentiva Polska Sp. z o.o.

ul. Bonifraterska 17

00-203 Warsaw

Tel. (22) 375 92 00

Date of last revision of the leaflet:December 2023