Bopaho

Package Leaflet: Information for the Patient

Bopaho, 62.5 mg, Coated Tablets

Bopaho, 125 mg, Coated Tablets

Bozentan

Read the package 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 you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, please inform your 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 bozentan, 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 activity) 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),
• (consult your doctor),
• , as you are not using effective contraception; see 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 you, tell your doctor.

Warnings and precautions

Your 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 during treatment

During Bopaho treatment, your 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 will 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

Tell your doctor or pharmacist about all medicines you are taking, or have recently taken, including those obtained without a prescription, as well as any medicines you plan to take.

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

Driving and using machines

Bopaho has no or negligible influence on the ability to drive and use machines. However, Bopaho may cause low blood pressure, which can cause dizziness, affect vision, and affect the ability to drive and use machines. Therefore, if you experience dizziness or blurred vision while taking Bopaho, do not drive, use tools, or operate machinery.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, ask your doctor or pharmacist for advice 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 the fetus. If you may become pregnant, your doctor will ask you to have a pregnancy test before starting Bopaho and regular tests during treatment.

Contraception

If you may become pregnant, you should use effective contraception while taking Bopaho. Your doctor or gynecologist will advise on effective methods of contraception during Bopaho treatment. Since Bopaho can make hormonal contraceptives ineffective (e.g., oral, injectable, implants, or transdermal patches), you cannot rely solely on this method of contraception. Therefore, when using hormonal contraceptives, you should also use a barrier method (e.g., female condom, diaphragm, contraceptive sponge, or your partner should also use a condom). Inside the Bopaho tablet pack, there is a Patient Alert Card. You should fill it out and bring it with you to your next visit so that your doctor or gynecologist can assess whether additional or other effective methods of contraception are needed. During Bopaho treatment, it is recommended to have monthly pregnancy tests for women of childbearing age. You must immediately inform your doctor if you become pregnant while taking Bopaho or plan to become pregnant in the near future.

Breastfeeding

If you are breastfeeding, you should immediately inform your 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 you are a male patient taking Bopaho, it is possible that this medicine may reduce the number of sperm in your semen. It cannot be excluded that this may affect your ability to father a child. If you have any questions or concerns about this, you should ask your 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 treating PAH or systemic scleroderma. This medicine should always be taken exactly as your doctor has told you. If you are not sure, ask your doctor or pharmacist.

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 your doctor will usually recommend taking a 125 mg tablet twice a day, depending on your response to Bopaho.

Children and adolescents

The recommended dose for children is only for the treatment of PAH. In children aged 1 year and older, treatment usually starts with a dose of 2 mg per kilogram of body weight twice a day (morning and evening). The dose is determined by your doctor.

Do not give Bopaho to children with a body weight below 31 kg; in this case, an alternative bozentan-containing medicine should be used.

If you feel that the effect of Bopaho is too strong or too weak, talk to your doctor, who may adjust the dose.

How to take Bopaho

Take the tablets twice a day (morning and evening), with water. The tablets can be taken with or without food.

Taking more Bopaho than prescribed

If you have taken 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 your tablets at the usual times. Do not take a double dose to make up for a forgotten dose.

Stopping Bopaho treatment

Suddenly stopping Bopaho treatment may lead to worsening of symptoms. Do not stop taking Bopaho unless your doctor tells you to. Your doctor may advise you to gradually reduce 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 ache),
• 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 you notice any of these symptoms, inform your doctor immediately.

Other side effects:

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

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

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

• flushing
• hypersensitivity reactions (including skin inflammation, itching, and rash)
• gastroesophageal reflux disease (stomach acid flowing back into the esophagus)
• diarrhea
• fainting (loss of consciousness)
• palpitations (rapid 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 fibrosis (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 you experience any side effects, including those not listed in this leaflet, please inform your 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. Tel.: 22 49 21 301, fax: 22 49 21 309, website: https://smz.ezdrowie.gov.pl. Side effects can also be reported to the marketing authorization holder or its representative in Poland. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Bopaho

Keep this medicine out of the 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 that month.

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 Bopaho contains

The active substance is bozentan.

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

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

The other ingredients are: cornstarch, povidone (K-30), sodium carboxymethylcellulose, type A; cornstarch, 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.

Pack sizes: 56 or 112 film-coated tablets.

Not all pack 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 about this medicine and its names in the Member States of 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