Bosentan Sun

Package leaflet: Information for the patient

Bosentan SUN 62.5 mg film-coated tablets, 125 mg film-coated tablets

Generic medicine
Please read 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 questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

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

Bosentan SUN contains bosentan, which naturally blocks a hormone called endothelin-1 (ET-1) that causes narrowing of blood vessels. Therefore, Bosentan SUN leads to the dilation of blood vessels and belongs to a class of medicines known as "endothelin receptor antagonists".

Bosentan SUN is used to treat:

• Pulmonary arterial hypertension (PAH): PAH is a disease characterized by severe narrowing of the blood vessels in the lungs, resulting in increased pressure in the blood vessels carrying blood from the heart to the lungs (pulmonary arteries). This pressure reduces the amount of oxygen that can pass into the blood through the lungs, making physical activity more difficult. Bosentan SUN widens the pulmonary arteries, making it easier for the heart to pump blood through them. This results in reduced blood pressure and alleviation of symptoms.

Bosentan SUN is used to treat PAH patients in WHO functional class III to improve exercise capacity (ability to perform physical activity) and symptoms. The "class" reflects the severity of the disease: "class III" means marked limitation in physical activity. Some benefits have also been observed in patients with PAH in class II. "Class II" indicates mild limitation in physical activity. The PAH for which Bosentan SUN is indicated may be:

• primary (without an identifiable cause or familial);

• caused by scleroderma (also known as systemic sclerosis, a disease characterized by abnormal growth of connective tissue supporting the skin and other organs);

• caused by congenital (inborn) heart defects with shunts (abnormal passages) leading to abnormal blood flow through the heart and lungs.

• Digital ulcers (sores on fingers and toes) in adult patients with a condition called scleroderma. Bosentan SUN reduces the number of new ulcers developing on fingers and toes.

2. What you need to know before taking Bosentan SUN

Do not take Bosentan SUN:

• if you are allergic to bosentan or to any of the other ingredients of this medicine (listed in section 6);
• if you have liver problems (consult your doctor);
• if you are pregnant or could become pregnant because you are not using reliable contraceptive methods. Read the information provided in the sections “Contraceptives” and “Other medicines and Bosentan SUN”;
• if you are being treated with cyclosporine A (a medicine used after organ transplantation or for the treatment of psoriasis).

If any of these situations apply to you, consult your doctor.
Warnings and precautions
Talk to your doctor or pharmacist before taking Bosentan SUN.
Tests required by your doctor before treatment:

• a blood test to check liver function;
• a blood test to monitor for anaemia (low haemoglobin);
• a pregnancy test if you are a woman of childbearing potential.

Abnormalities in liver function tests and anaemia (low haemoglobin) have been observed in some patients treated with bosentan.
Tests your doctor will prescribe during treatment
During treatment with Bosentan SUN, your doctor will regularly request blood tests to monitor for any changes in liver function and haemoglobin levels.
For all these tests, also refer to the Patient Information Card (included in the Bosentan SUN tablet packaging). It is important that you undergo these blood tests at regular intervals throughout the entire period of taking Bosentan SUN. It is recommended that you record on the Patient Information Card the date of your most recent test and the date of your next scheduled test (ask your doctor for this date) so that you do not forget when your next test is due.
Blood tests for liver function
These tests will be performed every month for the entire duration of treatment with Bosentan SUN.
After a dose increase, an additional test will be performed 2 weeks later.
Blood tests for anaemia
These tests will be performed every month for the first 4 months of treatment, and then every 3 months, as patients taking Bosentan SUN may develop anaemia.
If test results are abnormal, your doctor may decide to reduce the dose or discontinue treatment with Bosentan SUN and perform further tests to determine the cause.
Children and adolescents
Bosentan SUN is not recommended in pediatric patients with systemic sclerosis and active digital ulcers. See also section 3 “How to take Bosentan SUN”.
Other medicines and Bosentan SUN
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those not requiring a prescription. It is especially important to inform your doctor if you are taking:

• cyclosporine (a medicine used after transplants and for the treatment of psoriasis), which must not be used together with Bosentan SUN;
• sirolimus or tacrolimus, medicines used after transplants, as they are not recommended in combination with Bosentan SUN;
• glibenclamide (a medicine for diabetes), rifampicin (a medicine for tuberculosis), fluconazole (a medicine for fungal infections), ketoconazole (a medicine used for the treatment of Cushing's syndrome), or nevirapine (a medicine for HIV), as the use of these medicines is not recommended with Bosentan SUN;
• other medicines for HIV infection, which may require special monitoring when used with Bosentan SUN;
• hormonal contraceptives, which are not effective as the sole method of contraception when you are taking Bosentan SUN. Inside the Bosentan SUN tablet packaging, you will find a Patient Information Card which you must read carefully. Your doctor and/or gynaecologist will advise you on the appropriate contraceptive method for you;
• other medicines for pulmonary hypertension: sildenafil and tadalafil;
• warfarin (an anticoagulant);
• simvastatin (used to treat hypercholesterolaemia).

Pregnancy, breast-feeding and fertility
Women of childbearing potential
DO NOT take Bosentan SUN if you are pregnant or planning to become pregnant.
Pregnancy test
Bosentan SUN may harm the unborn child conceived before or during treatment. If you are a woman of childbearing potential, your doctor will ask you to take a pregnancy test before starting Bosentan SUN and to repeat it regularly during treatment with Bosentan SUN.
Contraceptives
If you are a woman of childbearing potential, you must use a reliable method of birth control (contraception) while taking Bosentan SUN. Your doctor or gynaecologist will advise you on reliable contraceptive methods during treatment with Bosentan SUN. Since Bosentan SUN may reduce the effectiveness of hormonal contraception (e.g. oral contraceptives, injectables, implants, or contraceptive patches), this method alone is not reliable. Therefore, if you use hormonal contraceptives, you must also use a barrier method (e.g. female condom, diaphragm, contraceptive sponge, or your partner must use a male condom). Inside the Bosentan SUN tablet packaging, you will find a Patient Information Card. You must complete this card and bring it to your next medical appointment, so that your doctor or gynaecologist can assess whether you need additional or alternative reliable contraceptive methods. It is recommended to perform a pregnancy test every month during treatment with Bosentan SUN if you are of childbearing age.
Inform your doctor immediately if you become pregnant during treatment with Bosentan SUN or if you plan to become pregnant in the near future.
Breast-feeding
Bosentan passes into breast milk. It is recommended that you stop breast-feeding if Bosentan SUN is prescribed, as it is unknown whether bosentan in breast milk could harm your baby. Discuss this with your doctor.
Fertility
If you are a man taking Bosentan SUN, this medicine may reduce sperm count. It cannot be ruled out that this may impair your ability to father a child. Consult your doctor if you have any questions about this.
Driving and using machines
Bosentan SUN does not affect or has a negligible effect on the ability to drive vehicles and use machines. However, Bosentan SUN may cause hypotension (low blood pressure), which can lead to dizziness, visual disturbances, and may affect your ability to drive or use machines. Therefore, if you experience dizziness or blurred vision while taking Bosentan SUN, do not drive and avoid using tools or machinery.
Bosentan SUN contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially ‘sodium-free’.

3. How to take Bosentan SUN

Treatment with Bosentan SUN must be initiated and monitored only by a physician experienced in the treatment of PAH or systemic sclerosis. Always take this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Bosentan SUN with food and drink
Bosentan SUN may be taken on an empty stomach or with food.
Recommended dose
Adults
In adults, treatment usually starts with one 62.5 mg tablet twice daily (morning and evening) for the first 4 weeks; thereafter, your doctor will usually recommend increasing to one 125 mg tablet twice daily, depending on your response to Bosentan SUN.
Children and adolescents
The recommended dose in children applies only for PAH. For children aged 1 year and older, treatment with Bosentan SUN is usually started at a dose of 2 mg per kg body weight twice daily (morning and evening). However, certain bosentan doses are not feasible in children weighing less than 31 kg. For these patients, a bosentan tablet with a lower dosage strength is required. Your doctor will advise on the subsequent dosage.
If you feel that the effect of Bosentan SUN is too strong or too weak, discuss this with your doctor to determine whether a dose adjustment is necessary.
How to take Bosentan SUN
Bosentan SUN tablets should be taken in the morning and in the evening, swallowed with water. The tablets may be taken on an empty stomach or with food.
If you take more Bosentan SUN than you should
If you take more tablets than prescribed, contact your doctor immediately.
If you forget to take Bosentan SUN
If you forget to take Bosentan SUN, take the missed dose as soon as you remember, and then continue taking the tablets at your usual times. Do not take a double dose to make up for the forgotten tablet.
If you stop taking Bosentan SUN
Sudden discontinuation of treatment with Bosentan SUN may lead to worsening of symptoms. Do not stop treatment with Bosentan SUN unless your doctor tells you to. Your doctor may instruct you to gradually reduce the dose over several days before stopping treatment completely.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The most serious side effects with Bosentan SUN are:

• Liver function abnormalities, which may affect more than 1 in 10 people.
• Anaemia (low blood values), which may affect up to 1 in 10 people. Occasionally, anaemia may require a blood transfusion.

Liver and blood test values must be monitored during treatment with Bosentan SUN (see section 2). It is important that you have these tests done as prescribed by your doctor.
Signs of impaired liver function include:

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

If you notice any of these signs, contact your doctor immediately.
Other side effects:
Very common (may affect more than 1 in 10 people):

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

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

• Flushed appearance or skin flushing
• Hypersensitivity reactions (including skin inflammation, itching, and rash)
• Gastroesophageal reflux disease (acid reflux)
• Diarrhoea
• Syncope (fainting)
• Palpitations (fast or irregular heartbeat)
• Low blood pressure
• Nasal congestion.

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

• Thrombocytopenia (low platelet count in the blood)
• Neutropenia/leucopenia (low white blood cell count in the blood)
• Elevated liver function test values associated with hepatitis (liver inflammation), including possible exacerbation of latent hepatitis and/or jaundice (yellowing of the skin or whites of the eyes).

Rare (may affect up to 1 in 1,000 people):

• Anaphylaxis (generalised allergic reaction), angioedema (swelling, most commonly around eyes, lips, tongue or throat)
• Liver cirrhosis (scarring), liver failure (severe impairment of liver function).

Not known (frequency cannot be estimated from the available data):

• Blurred vision.

Side effects in children and adolescents
The side effects reported in children treated with bosentan are the same as those in adults.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via the national reporting system at: www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa .
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Bosentan SUN

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister or bottle and on the carton after Exp. The expiry date refers to the last day of that month.
Validity period after first opening (bottles only): 50 days.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Bosentan SUN contains

• The active substance is bosentan. Each tablet contains 62.5/125 mg of bosentan.
• The other components are: maize starch, pregelatinized starch, sodium starch glycolate, povidone K-30, glyceryl dibehenate, magnesium stearate.

The film coating (Opadry Yellow 21K520019) contains: hypromellose (E464), titanium dioxide (E171), triacetin, talc (E553b), ethylcellulose, yellow iron oxide (E172), red iron oxide (E172).

Description of the appearance of Bosentan SUN and contents of the pack

Bosentan SUN 62.5 mg film-coated tablets
Bosentan SUN 62.5 mg film-coated tablets are film-coated, round, biconvex tablets ranging in colour from light peach to peach, with "62.5" engraved on one side and smooth on the other. The tablets have a diameter of approximately 5.9 mm.
PVC/PE/PVdC/Al blisters containing 14 and 56 film-coated tablets.
Unit dose perforated PVC/PE/PVdC/Al blisters containing 14 x 1 and 56 x 1 film-coated tablets.

Bosentan SUN 125 mg film-coated tablets
Bosentan SUN 125 mg film-coated tablets are film-coated, oval, biconvex tablets ranging in colour from light peach to peach, with "125" engraved on one side and smooth on the other. The tablets have a length of approximately 11.0 mm and a width of 5.0 mm.
PVC/PE/PVdC/Al blisters containing 14, 56 and 120 film-coated tablets.
Unit dose perforated PVC/PE/PVdC/Al blisters containing 14 x 1, 56 x 1 and 120 x 1 film-coated tablets.

Bosentan SUN 62.5 mg and 125 mg film-coated tablets
HDPE bottles containing 56 and 100 film-coated tablets.
The HDPE bottle is made of white opaque high-density polyethylene, includes a sealed protective layer and a child-resistant screw cap, and contains a silica gel desiccant sachet. DO NOT SWALLOW the contents of the sachet.

Not all pack sizes may be marketed.

Marketing Authorization Holder
Sun Pharma France
31, Rue Des Poissonniers
92200 Neuilly sur Seine
France

Local Representative
Sun Pharma Italia S.r.l.
Viale Giulio Richard, 3
20143 Milano
Italy

Manufacturers responsible for batch release
Sun Pharmaceutical Industries Europe B.V.
Polarisavenue 87
2132JH Hoofddorp
The Netherlands

Terapia S.A.
Str. Fabricii Nr 124
400 632 Cluj-Napoca
Romania

ALKALOIDA Chemical Company Zrt.
Kabay János u. 29
H-4440 Tiszavasvári
Hungary

This medicinal product is authorized in the European Economic Area Member States under the following names:
Germany: BOSENTAN BASICS 62.5 mg (125 mg) Filmtabletten
France: BOSENTAN SUN 62.5 mg, (125 mg) comprimé pelliculé
Italy: Bosentan SUN
Spain: Bosentan Sun 62.5 mg (125 mg) comprimidos recubiertos con película EFG
Romania: Bosentan Terapia 125 mg comprimate filmate
Poland: Bosentan Ranbaxy (125 mg)