Bosentan ranbaxy

DE/H/4181/001-002/IB/014

Package leaflet: Information for the user

Bosentan Ranbaxy, 125 mg, film-coated tablets
Bosentanum
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, please ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you personally. Do not give it to others. It may harm other people, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, please tell your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet

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

1. What Bosentan Ranbaxy is and what it is used for

Bosentan Ranbaxy contains bosentan, which blocks a naturally occurring hormone called
endothelin-1 (ET-1) that causes narrowing of blood vessels. Therefore, bosentan causes
dilation of blood vessels; this medicine belongs to a group of medicines known as
"endothelin receptor antagonists".
Bosentan Ranbaxy 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.
Bosentan dilates the pulmonary arteries, allowing the heart to pump blood more easily. As a
result, blood pressure is reduced and symptoms improve.
Bosentan Ranbaxy is used in the treatment of patients with PAH in WHO functional class III
to improve exercise capacity (ability to perform physical activity) and relieve symptoms. The
"functional 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 functional class II. Class II is associated with slight limitation of physical activity.
The PAH treated with Bosentan Ranbaxy may be:

• idiopathic (of unknown cause) or heritable;
• associated with scleroderma (also called systemic sclerosis, a disease characterized by abnormal growth of connective tissue supporting the skin and other organs);
• associated with congenital heart defects involving shunts (abnormal blood flow) between the heart and lungs.

Digital ulcers: (sores on the fingertips and toes) in adult patients with a disease called
systemic sclerosis. Bosentan Ranbaxy reduces the number of new digital ulcers appearing
on the fingers and toes.
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2. Important information before taking Bosentan Ranbaxy

When not to take Bosentan Ranbaxy

• if the patient is allergic to bosentan or any of the other ingredients of this medicine (listed in section 6)
• in case of liver disease (consult the treating physician)
• if the patient is pregnant or may become pregnant because she is not using effective contraception; please refer to the information provided in the sections “Contraceptive methods” and “Bosentan Ranbaxy with other medicines”
• if the patient is taking cyclosporine A (a medicine used after transplantation or in the treatment of psoriasis)

If any of the above situations apply to the patient, he or she should inform the doctor.

Warnings and precautions

Before starting treatment with Bosentan Ranbaxy, discuss this with your doctor or pharmacist.

Tests your doctor will perform before starting treatment

• blood test to assess liver function
• blood test to rule out anaemia (low haemoglobin levels)
• pregnancy test in women of childbearing potential

In some patients taking bosentan, abnormal liver function test results and anaemia (low haemoglobin levels) have been observed.

Tests your doctor will perform during treatment

During treatment with Bosentan Ranbaxy, your treating doctor will order regular blood tests to monitor changes in liver function and haemoglobin levels.

A description of all required tests is also provided in the Patient Alert Card (included inside the Bosentan Ranbaxy tablet packaging). It is important to carry out regular blood tests while taking Bosentan Ranbaxy. It is recommended that the patient record the date of the last and the next scheduled blood test on the Patient Alert Card (according to the doctor’s instructions) to avoid missing an appointment.

Blood tests to monitor liver function

These tests will be performed once a month during treatment with Bosentan Ranbaxy. After a dose increase, an additional test should be performed after 2 weeks.

Blood tests to rule out anaemia

These tests will be performed once a month during the first 4 months of treatment, then every 3 months, as anaemia may occur in patients taking Bosentan Ranbaxy.

If test results are abnormal, your treating doctor may decide to reduce the dose or discontinue treatment with Bosentan Ranbaxy and perform additional tests to determine the cause.

Children and adolescents

Bosentan Ranbaxy is not recommended for use in children and adolescents with systemic sclerosis and digital ulcers. See also section 3. “How to take Bosentan Ranbaxy”.

Bosentan Ranbaxy with other medicines

Inform your doctor or pharmacist about all medicines you are currently taking or have recently taken, including those obtained without a prescription. In particular, inform your doctor if you are taking:

• cyclosporine (a medicine used after transplantation or in the treatment of psoriasis), which must not be used together with Bosentan Ranbaxy
• sirolimus or tacrolimus, medicines used after transplantation, as they are not recommended to be used together with Bosentan Ranbaxy
• glibenclamide (a medicine for diabetes), rifampicin (a medicine for tuberculosis), fluconazole (an antifungal medicine), ketoconazole (a medicine used in the treatment of Cushing's syndrome), or nevirapine (a medicine for HIV infection), as these medicines are not recommended to be used together with Bosentan Ranbaxy
• other medicines for HIV infection, which may require special monitoring when used concomitantly with Bosentan Ranbaxy
• hormonal contraceptives, which are ineffective as the sole method of contraception during treatment with Bosentan Ranbaxy. The Patient Alert Card, included inside the Bosentan Ranbaxy tablet packaging, should be read carefully. Your treating doctor and/or gynaecologist will determine the most appropriate contraceptive method for you
• other medicines used to treat pulmonary arterial hypertension: sildenafil and tadalafil
• warfarin (an anticoagulant medicine)
• simvastatin (a medicine used to treat hypercholesterolaemia)

Pregnancy, breastfeeding and fertility

Women of childbearing potential

DO NOT take Bosentan Ranbaxy if you are pregnant or planning to become pregnant.

Pregnancy tests

Bosentan Ranbaxy may be harmful to fetuses conceived before or during treatment. If you are of childbearing potential, your doctor will request a pregnancy test before starting treatment with Bosentan Ranbaxy, and regular repeat testing during treatment.

Contraceptive methods

If you are of childbearing potential, you must use an effective method of contraception during treatment with Bosentan Ranbaxy. Your treating doctor or gynaecologist will recommend using effective contraceptive methods during treatment with Bosentan Ranbaxy. Bosentan Ranbaxy may reduce the effectiveness of hormonal contraceptives (e.g. oral, injectable, implants or skin patches), therefore using hormonal contraception alone is not effective. For this reason, when using hormonal contraceptives, a barrier method (e.g. female condom, intrauterine device, contraceptive sponge, or male partner using a condom) must also be used.

Inside the Bosentan Ranbaxy packaging, there is a Patient Alert Card. Please complete it and bring it to your next doctor’s visit so that your treating doctor or gynaecologist can assess whether additional or alternative effective contraceptive methods are needed. Monthly pregnancy tests are recommended in women of childbearing potential during treatment with Bosentan Ranbaxy.

Inform your doctor immediately if you become pregnant while taking Bosentan Ranbaxy, or if you plan to become pregnant in the near future.

Breastfeeding

Bosentan passes into breast milk. Breastfeeding should be discontinued during treatment with Bosentan Ranbaxy, as it is unknown whether bosentan in breast milk may harm the infant. Please discuss this with your doctor.

Fertility

If a male patient is taking Bosentan Ranbaxy, the medicine may reduce sperm count in semen. It cannot be excluded that this may affect the ability to father a child. If you have any questions or concerns about this, consult your doctor.

Driving and operating machinery

Bosentan Ranbaxy has no effect or a negligible effect on the ability to drive and operate machinery. However, Bosentan Ranbaxy may cause hypotension (low blood pressure), which may lead to dizziness, blurred vision and may affect the ability to drive and operate machinery. Therefore, if dizziness or blurred vision occurs during treatment with Bosentan Ranbaxy, you must not drive, use tools or operate machinery.

Bosentan Ranbaxy contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e. the medicine is considered to be “sodium-free”.

3. How to use Bosentan Ranbaxy

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

Taking Bosentan Ranbaxy with food and drink
Bosentan Ranbaxy may be taken with or without food.

Recommended dose
Adults
In adult patients, treatment usually starts with a 62.5 mg tablet twice daily (morning and evening) for the first 4 weeks. Afterwards, your doctor will usually recommend increasing to a 125 mg tablet twice daily, depending on the patient's response to Bosentan Ranbaxy.

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 Ranbaxy usually starts at a dose of 2 mg per kg body weight twice daily (morning and evening). However, in children weighing less than 31 kg, administration of certain bosentan doses may not be feasible. The physician will determine the appropriate dose.

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

How to take Bosentan Ranbaxy
Take Bosentan Ranbaxy in the morning and evening with water. Tablets may be taken with or without food.

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

If you forget to take Bosentan Ranbaxy
If you forget to take a dose of Bosentan Ranbaxy, 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 forgotten dose.

Stopping Bosentan Ranbaxy
Suddenly stopping treatment with Bosentan Ranbaxy may worsen symptoms. Do not discontinue treatment with Bosentan Ranbaxy unless instructed by your doctor. Your doctor may advise you to gradually reduce the dose over several days before completely stopping the medicine.

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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 experience them.
The most serious adverse reactions with Bosentan Ranbaxy are:

• Liver function abnormalities, which may occur in more than 1 in 10 patients.
• Anaemia (low red blood cell count), which may occur in up to 1 in 10 patients. Blood transfusions may sometimes be necessary in cases of anaemia.

Liver function tests and blood counts will be monitored during treatment with
Bosentan Ranbaxy (see section 2). It is important that patients undergo these tests as recommended
by their doctor.
Symptoms of liver function abnormalities include:

• 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).

If patients notice any of these symptoms, they should inform their doctor immediately.
Other adverse reactions:
Very common (may occur in more than 1 in 10 people):

• Headache
• Oedema (swelling of legs and ankles or other signs of fluid retention in the body) Common (may occur in up to 1 in 10 people):
• Flushing (sudden feeling of warmth and redness of the skin)
• Hypersensitivity reactions (including skin inflammation, itching and rash)
• Gastro-oesophageal reflux disease (reflux of stomach contents)
• Diarrhoea
• Fainting
• Palpitations (fast or irregular heartbeat)
• Low blood pressure
• Nasal congestion

Uncommon (may occur in up to 1 in 100 people):

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

Rare (may occur in up to 1 in 1000 people):

• Anaphylaxis (generalised allergic reaction), angioedema (swelling typically affecting the eyes, lips, tongue or throat)

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• Liver fibrosis (cirrhosis), liver failure (severe impairment of liver function)

Frequency unknown (frequency cannot be estimated from available data):

• Blurred vision

Adverse reactions in children and adolescents
Adverse reactions observed in children treated with bosentan are the same as those in
adults.
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, patients should inform their doctor, pharmacist, or nurse.
Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, 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 the medicine.

5. How to store Bosentan Ranbaxy

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister, bottle, and carton after "EXP". The expiry date refers to the last day of the specified month.
Shelf-life after first opening (bottles only): 50 days
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Proper disposal helps protect the environment.

6. Contents of the pack and other information

What Bosentan Ranbaxy contains

• The active substance is bosentan. Each tablet contains 125 mg of bosentan.
• The other ingredients are: corn starch, pregelatinized corn starch, sodium carboxymethyl starch, povidone K-30, glyceryl dibehenate, magnesium stearate.

The tablet coating (Opadry 21K520019 Yellow) contains: hypromellose, titanium dioxide (E 171), triacetin, talc, ethylcellulose, yellow iron oxide (E 172), red iron oxide (E 172).

What Bosentan Ranbaxy looks like and contents of the pack
Bosentan Ranbaxy 125 mg are film-coated tablets, light peach to peach-coloured, oval, biconvex, with "125" embossed on one side and smooth on the other side, approximately 11.0 mm in length and 5.0 mm in width.
Blister packs made of PVC/PE/PVDC/Aluminium in cardboard boxes containing:
14, 56 and 120 film-coated tablets.
Single-dose perforated blisters made of PVC/PE/PVDC/Aluminium in cardboard boxes containing:
14 x 1, 56 x 1 and 120 x 1 film-coated tablets.
HDPE bottles in cardboard boxes containing 56 and 100 film-coated tablets.
White, opaque HDPE high-density polyethylene bottles with induction seal and child-resistant PP cap, containing a sachet with moisture-absorbing silica gel.
DO NOT SWALLOW the contents of the sachet.
Not all pack sizes may be marketed.

This medicinal product is authorised in the European Economic Area and the United Kingdom (Northern Ireland) under the following names:
Germany: BOSENTAN BASICS 125 mg Filmtabletten
France: BOSENTAN SUN 125 mg comprimé pelliculé
Italy: Bosentan Sun
Spain: Bosentan Sun 125 mg comprimidos recubiertos con película EFG
Romania: Bosentan Terapia 125 mg comprimate filmate

Marketing Authorisation Holder
Ranbaxy (Poland) Sp. z o.o.
ul. Idzikowskiego 16
00-710 Warsaw
Poland

Manufacturer/Importer
Terapia S.A.
Str. Fabricii nr. 124
400632 Cluj-Napoca
Romania
Sun Pharmaceutical Industries Europe B.V.
Polarisavenue 87
2132JH Hoofddorp
The Netherlands
Alkaloida Chemical Company Zrt.
Kabay János u. 29
4440 Tiszavasvári
Hungary