Bosentan Accord Pharma

Patient Information Leaflet

Bosentan Accordpharma 32 mg dispersible tablets

Bosentan
Generic medicine
Please read all of this leaflet carefully before you start 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 or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, 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, inform your doctor or pharmacist.

Contents of this leaflet:

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

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

Bosentan Accordpharma tablets contain bosentan, which blocks a naturally occurring hormone called endothelin-1 (ET-1) that causes narrowing of blood vessels. Bosentan Accordpharma therefore causes blood vessels to widen and belongs to a class of medicines known as endothelin receptor antagonists.
Bosentan Accordpharma is used to treat:

• Pulmonary arterial hypertension (PAH): PAH is a disease characterised 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 Accordpharma widens the pulmonary arteries, making it easier for the heart to pump blood through them; this leads to reduced blood pressure and alleviation of symptoms.

Bosentan Accordpharma 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 PAH patients in class II. "Class II" means slight limitation in physical activity. The PAH for which Bosentan Accordpharma is indicated may be:

• idiopathic (without an identifiable cause) or heritable;

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

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

• Digital ulcers: (sores on the fingers and toes) in adult patients with scleroderma. Bosentan Accordpharma reduces the number of new ulcers developing on the fingers and toes.

2. What you should know before taking Bosentan Accordpharma

Do not take Bosentan Accordpharma:

• 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. Please read the information provided under “Contraceptives” and “Other medicines and Bosentan Accordpharma”
• if you are being treated with cyclosporine A (a medicine used after organ transplantation or for the treatment of psoriasis)

In any of these cases, inform your doctor.
Warnings and precautions
Tests required by your doctor before treatment

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

In some patients treated with bosentan, abnormalities in liver function tests and anaemia (low haemoglobin) have been observed.

Tests your doctor will prescribe during treatment
During treatment with Bosentan Accordpharma, your doctor will regularly request blood tests to monitor any changes in liver function and haemoglobin levels.
For all these tests, refer also to the Patient Information Leaflet (included in your package of Bosentan Accordpharma). It is important that you undergo these blood tests at regular intervals throughout the entire period of Bosentan Accordpharma administration. It is recommended to record on the Patient Information Card the date of your most recent test and also the date of your next scheduled test (ask your doctor for this date), so as not to forget when your next test is due.
Blood tests for liver function
These will be performed every month for the entire duration of treatment with Bosentan Accordpharma. After a dose increase, an additional test will be performed after 2 weeks.
Blood tests for anaemia
These will be performed every month for the first 4 months of treatment and then every 3 months, as patients taking Bosentan Accordpharma may develop anaemia.
If these results are abnormal, your doctor may decide to reduce the dose or discontinue treatment with Bosentan Accordpharma and carry out further tests to determine the cause.
Children and adolescents
Bosentan Accordpharma is not recommended in paediatric patients with systemic sclerosis and active digital ulcers. Please also see section 3. How to take Bosentan Accordpharma.
Other medicines and Bosentan Accordpharma
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 (a medicine used after organ transplants and for the treatment of psoriasis), which must not be used together with Bosentan Accordpharma.
• sirolimus or tacrolimus, which are medicines used after transplants; their use together with Bosentan Accordpharma is not recommended.
• 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 together with Bosentan Accordpharma is not recommended.
• other medicines for the treatment of HIV infection, which may require special monitoring when used together with Bosentan Accordpharma.
• hormonal contraceptives, which are not effective as the sole method of contraception when you are taking Bosentan Accordpharma. Inside the package of Bosentan Accordpharma you will find a Patient Information Card that you should read carefully. Your general practitioner and/or gynaecologist will determine the appropriate contraceptive method for you.
• other medicines for the treatment of pulmonary hypertension: sildenafil and tadalafil;
• warfarin (an anticoagulant);
• simvastatin (used to treat hypercholesterolaemia). Driving and using machines

Bosentan Accordpharma does not alter or alters only negligibly the ability to drive and use machines. However, Bosentan Accordpharma may cause hypotension (lowering of blood pressure) which may make you feel unstable and affect your vision and your ability to drive and use machines. Therefore, if you experience dizziness or blurred vision during treatment with Bosentan Accordpharma, do not drive or operate any tools or machinery.
Women of childbearing potential
DO NOT take Bosentan Accordpharma if you are pregnant or planning a pregnancy.
Pregnancy test
Bosentan Accordpharma 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 Accordpharma and to repeat it regularly during treatment with Bosentan Accordpharma.
Contraceptives
If you are a woman of childbearing potential, use a reliable method of birth control (contraception) while taking Bosentan Accordpharma. Your doctor or gynaecologist will advise you on reliable contraceptive methods while taking Bosentan Accordpharma. Since Bosentan Accordpharma may render hormonal contraception ineffective (e.g. oral, injectable, implantable or transdermal patch contraceptives), 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 your package of Bosentan Accordpharma you will find a Patient Information Card. You should complete this card and bring it to your doctor at your next visit, 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 Accordpharma if you are of childbearing age.
Inform your doctor immediately if you become pregnant during treatment with Bosentan Accordpharma or if you plan to become pregnant in the near future.
Breast-feeding
Bosentan Accordpharma passes into breast milk. It is recommended to stop breast-feeding if Bosentan Accordpharma is prescribed, as it is not known whether Bosentan Accordpharma in breast milk could harm your baby. Talk to your doctor if you have any questions about this.
Fertility
If you are a man taking bosentan, this medicine may reduce sperm count. It cannot be excluded that this could impair your ability to father a child. Talk to your doctor if you have any questions about this.
Bosentan Accordpharma contains aspartame and sodium
This medicine contains 3.7 mg of aspartame per dispersible tablet. Aspartame is a source of phenylalanine. It may be harmful to you if you have phenylketonuria (PKU), a rare genetic disorder causing accumulation of phenylalanine because the body cannot eliminate it properly.
This medicine contains less than 0.07 mmol (1.52 mg) of sodium per tablet, i.e. essentially ‘sodium-free’.

3. How to take Bosentan

Treatment with Bosentan Accordpharma should be initiated and monitored only by a doctor experienced in the treatment of PAH or systemic sclerosis. Take this medicine exactly as your doctor has instructed. If you have any doubts, consult your doctor or pharmacist.
Bosentan Accordpharma with food and drink
Bosentan Accordpharma may be taken on an empty stomach or with food.
Recommended dose
Adults
In adults, treatment usually starts with one 62.5 mg tablet taken twice daily (morning and evening) for the first 4 weeks. After this period, your doctor will usually recommend taking one 125 mg tablet twice daily, depending on your response to Bosentan Accordpharma.
Use in children and adolescents
The recommended dose in children applies only for PAH. For children aged 1 year and older, treatment with Bosentan Accordpharma usually starts at 2 mg per kg body weight taken twice daily (morning and evening). Your doctor will advise on subsequent dosing. If necessary, the dispersible tablet may be divided along the scored lines into four equal parts.
If you feel that the effects of Bosentan Accordpharma are too strong or too weak, talk to your doctor to determine whether a dose adjustment is needed.
How to take Bosentan Accordpharma
Take the tablets (morning and evening) with water. Tablets may be taken with or without food.
Each Bosentan Accordpharma dispersible tablet can be dissolved in water to make a liquid medicine. To do this, place the tablet in a spoon with a small amount of water, using enough water to cover the entire tablet. Wait about one minute until the tablet has completely dissolved, then swallow all the liquid. To ensure you have taken the full dose, add a little more water to the spoon and drink all the liquid. If possible, drink a glass of water afterwards to make sure you have taken all the medicine.
If necessary, the dispersible tablet can be divided by breaking it along the scored lines on its surface. Hold the tablet between your thumb and index finger on either side of the line, with the line facing upwards. Break the tablet into two halves along the line (see the following figure).

If you take more Bosentan Accordpharma than you should
If you have taken more tablets than prescribed, contact your doctor immediately.
If you forget to take Bosentan Accordpharma
If you forget to take Bosentan Accordpharma, take a tablet as soon as you remember, then continue taking your tablets at the usual times. Do not take a double dose to make up for forgotten doses.
If you stop taking Bosentan Accordpharma
Stopping treatment with Bosentan Accordpharma suddenly may cause your symptoms to worsen. Do not stop treatment unless instructed by your doctor. Your doctor may advise you to gradually reduce the dose over several days before stopping treatment completely.
If you have any questions about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.

The most serious side effects associated with Bosentan Accordpharma are:

• Impaired liver function, which may affect more than 1 in 10 people
• Anaemia (reduction in blood test 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 Accordpharma (see section 2). It is important that you have these tests performed as prescribed by your doctor.

Signs of improper liver function include:

• nausea (feeling like vomiting)
• 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 syndrome (joint and muscle pain with fever)

If you notice any of these signs, tell your doctor immediately.

Other side effects:

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

• headache
• oedema (swelling of the legs and ankles or other signs due to fluid retention)

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

• Flushed appearance or skin redness
• Hypersensitivity reactions (including skin inflammation, itching, and rash)
• Gastro-oesophageal 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 number of platelets in the blood)
• Neutropenia/leucopenia (low number of white blood cells)
• Changes in liver function tests associated with hepatitis (liver inflammation), including possible worsening of underlying 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 the eyes, lips, tongue, or throat)
• Liver cirrhosis (scarring), liver failure (severe impairment of liver function)

Blurred vision has also been reported, with a frequency not known (the frequency cannot be determined from the available data).

Side effects in children and adolescents

The side effects reported in children treated with Bosentan Accordpharma 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 Italian Medicines Agency (Agenzia Italiana del Farmaco) website: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Bosentan Accordpharma

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after "Exp".
This medicine does not require any special storage conditions.
Remaining parts of a divided dispersible tablet may be stored at room temperature and
must be used within 7 days.
Do not dispose of medicines 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 Accordpharma contains
The active substance is bosentan monohydrate. Each dispersible tablet contains 32 mg of bosentan (as
monohydrate). The other components are microcrystalline cellulose, sodium croscarmellose, povidone K 30,
magnesium stearate, calcium hydrogen phosphate, tartaric acid, tutti frutti flavour, aspartame (please
read further information at the end of section 2), acesulfame potassium.

Description of the appearance of Bosentan Accordpharma and the contents of the pack
The 32 mg dispersible tablets of Bosentan Accordpharma are dispersible tablets, pale yellow to whitish in colour,
shaped like a clover, quadrisected on one side and marked with "NC" and "1" on the other side.
The 32 mg dispersible tablets of Bosentan Accordpharma are packaged in aluminium/aluminium blisters
containing 14 dispersible tablets. Packs contain 56 dispersible tablets.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Accord Healthcare S.L.U.
World Trade Center, Moll de Barcelona, s/n,
Edifici Est, 6th Floor,
08039 Barcelona,
Spain

Manufacturer
Accord Healthcare B.V.
Winthontlaan 200, Utrecht,
3526 KV, The Netherlands
Accord Healthcare Polska Sp. z o.o.
ul. Lutomierska 50, Pabianice, Lodzkie
95-200, Poland
Accord Healthcare single member S.A.
64th Km National Road Athens, Lamia,
Schimatari, 32009, Greece