Bosentan Mylan

Package leaflet: Information for the patient

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

bosentan
Generic medicine
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 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, because it could be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

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

Bosentan Mylan film-coated tablets of 62.5 mg or 125 mg contain bosentan, which blocks a natural hormone called endothelin-1 (ET-1) that causes narrowing of blood vessels. Bosentan therefore widens blood vessels and belongs to a class of medicines known as "endothelin receptor antagonists".
Bosentan Mylan 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 arterial blood vessels (the pulmonary arteries) that carry blood from the heart to the lungs. This pressure reduces the amount of oxygen that can pass into the blood through the lungs, making physical activity more difficult. Bosentan 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 Mylan is used to treat patients with pulmonary arterial hypertension (PAH) in class III to improve exercise capacity and symptoms. The "class" indicates the severity of the disease: "class III" means marked limitation of physical activity. Some improvements have also been observed in patients with PAH class II. "Class II" refers to slight limitation of physical activity.
The PAH for which Bosentan Mylan is indicated may be:

• primary (without an identified cause or family history);
• caused by scleroderma (also called systemic sclerosis, a disorder characterised by abnormal growth of connective tissue supporting the skin and other organs);
• caused by congenital cardiac defect (present from birth) with shunts (abnormal connections) causing abnormal blood flow between the heart and lungs.

Bosentan Mylan is also used to treat digital ulcers (sores on the fingers and toes) in adult patients with scleroderma. Bosentan prevents the formation of new ulcers on the fingers and toes.
If you do not feel well or if your symptoms worsen after taking Bosentan Mylan, you must inform your doctor.

2. What you need to know before taking Bosentan Mylan

Do not take Bosentan Mylan:

• 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
• if you are being treated with cyclosporine A (a medicine used after organ transplantation or for the treatment of psoriasis)
• if you are pregnant or could become pregnant because you are not using reliable contraceptive methods. Read the information provided under "Contraceptives" and "Other medicines and Bosentan Mylan".

If any of these conditions apply to you, consult your doctor.

Warnings and precautions

Tests required by your doctor before starting 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 age.

Abnormal blood test results regarding liver function and anaemia (low haemoglobin levels) have been observed in some patients treated with bosentan.

Tests your doctor will prescribe during treatment

During treatment with Bosentan Mylan, 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 Alert Card (included in your pack of Bosentan Mylan tablets). It is important that you undergo these blood tests at regular intervals throughout the entire period of Bosentan Mylan administration. It is recommended that you record on the Patient Alert Card the date of your most recent test and 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 Mylan. An additional test will be performed 2 weeks after any dose increase.

Blood tests for anaemia

These will be performed every month for the first 4 months of treatment and then every 3 months thereafter, as patients taking bosentan may develop anaemia.

If these test results are abnormal, your doctor may decide to reduce the dose or discontinue treatment with Bosentan Mylan and carry out further tests to determine the cause.

Children and adolescents

Bosentan is not recommended in paediatric patients with systemic sclerosis and active digital ulcers. Please also refer to section 3, "How to take Bosentan Mylan".

Other medicines and Bosentan Mylan

Inform your doctor or pharmacist if you are currently taking, have recently taken, or might take any other medicines, including those without a prescription. It is especially important to inform your doctor if you are taking:

• cyclosporine A (a medicine used after organ transplantation and for the treatment of psoriasis) – see section "Do not take Bosentan Mylan"
• hormonal contraceptives (which are not effective as the sole method of contraception when you are taking Bosentan Mylan). Inside the pack of Bosentan Mylan tablets you will find a Patient Alert Card that you must read carefully. Your doctor and/or gynaecologist will determine the appropriate contraceptive method for you
• glibenclamide (for the treatment of diabetes – as this combination may increase the risk of side effects)
• tacrolimus, sirolimus, or any other medicine used to prevent rejection of transplanted organs (as these medicines may increase bosentan blood levels)
• fluconazole, ketoconazole, itraconazole, and voriconazole (for the treatment of fungal infections – as these medicines may increase bosentan blood levels)
• simvastatin (used for the treatment of hypercholesterolaemia, high cholesterol levels – as bosentan may reduce blood levels of this medicine)
• warfarin (an anticoagulant – as bosentan may reduce blood levels of this medicine)
• other medicines for the treatment of pulmonary hypertension: sildenafil and tadalafil (also used to treat erectile dysfunction – as bosentan may reduce blood levels of these medicines)
• rifampicin (for the treatment of tuberculosis – as this medicine may reduce the effectiveness of bosentan)
• carbamazepine, phenobarbital, phenytoin (medicines commonly used to treat epilepsy) or St. John’s wort (used to treat depression) – as these medicines may reduce the effectiveness of bosentan
• ritonavir and lopinavir, nevirapine, or other medicines for the treatment of HIV infection.

Pregnancy, breastfeeding and fertility

Women of childbearing potential

DO NOT take Bosentan Mylan if you are pregnant or planning a pregnancy.

Pregnancy test

Bosentan may harm the unborn child conceived before or during treatment. Your doctor will require women of childbearing age to have a pregnancy test before starting Bosentan Mylan and then every month during treatment with Bosentan Mylan.

Contraceptives

If you could become pregnant, you must use a reliable method of birth control (contraception) during treatment with Bosentan Mylan. Your doctor or gynaecologist will advise you on reliable contraceptives to use during therapy with Bosentan Mylan. Since bosentan may render hormonal contraception ineffective (e.g. oral, injectable, implantable contraceptives 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 your pack of Bosentan Mylan tablets you will find a Patient Alert 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 Mylan if you are of childbearing age.

Inform your doctor immediately if you become pregnant during treatment with Bosentan Mylan or if you plan to become pregnant in the near future.

Breastfeeding

Bosentan Mylan passes into breast milk. It is recommended to stop breastfeeding if Bosentan Mylan is prescribed, as it may harm your baby. Speak with your doctor if you have any questions about this.

Fertility

If you are a man taking bosentan, this medicine may reduce sperm count. This could potentially impair your ability to father a child. Talk to your doctor if you have any questions about this.

Driving and using machines

Bosentan does not affect or affects negligibly the ability to drive and use machines. However, bosentan may cause hypotension (low blood pressure), which can lead to dizziness, visual disturbances, and may affect your ability to drive and use machinery. Therefore, if you experience dizziness or blurred vision while taking bosentan, do not drive or operate tools or machinery.

Bosentan Mylan contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e. essentially 'sodium-free'.

3. How to take Bosentan Mylan

Treatment with Bosentan Mylan must be initiated and monitored only by a physician experienced in the treatment of PAH or systemic sclerosis. Take this medicine exactly as prescribed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
If you feel that the effect of Bosentan Mylan is too strong or too weak, contact your doctor to determine whether the dose needs to be adjusted.
Recommended dose
Use in adults
In adults, treatment typically starts with a recommended dose of 62.5 mg twice daily (morning and evening) for the first 4 weeks; thereafter, your doctor will usually recommend increasing to 125 mg twice daily, depending on your response to Bosentan Mylan.
Use in children and adolescents
The recommended dose in children applies only for the treatment of pulmonary arterial hypertension. For children aged 1 year and older, the recommended starting dose of bosentan is normally 2 mg per kg of body weight twice daily (morning and evening). Your doctor will advise you on the exact dose to give your child.
Other formulations of this medicine may be more suitable for children, for individuals with low body weight, or for those who have difficulty swallowing; please consult your doctor or pharmacist.
How to take Bosentan Mylan
Take the tablets (morning and evening) with water. The tablets may be taken with or without food.
If you take more Bosentan Mylan than you should
If you have taken more tablets than prescribed, contact your doctor immediately.
You may experience symptoms such as headache, feeling unwell, low blood pressure (which may make you feel weak or dizzy), sweating, and blurred vision.
If you forget to take Bosentan Mylan
If you forget to take Bosentan Mylan, take the missed dose as soon as you remember, then continue taking the tablets at your regular times. Do not take a double dose to make up for forgotten doses.
If you stop taking Bosentan Mylan
Stopping treatment with Bosentan Mylan abruptly may lead to worsening of symptoms. Do not discontinue treatment with Bosentan Mylan 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 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 are:

• Impairment of liver function, which may affect more than 1 in 10 people
• Anaemia (low red blood cell count), which may affect up to 1 in 10 people. Anaemia may occasionally require a blood transfusion.

Your liver and blood values will be monitored during treatment with bosentan (see section 2). It is important to have these tests performed as directed by your doctor.
Possible signs of impaired liver function include:

• Nausea (feeling sick)
• Vomiting
• Fever (high temperature)
• Stomach (abdominal) pain
• Jaundice (yellowing of the skin or the whites of the eyes)
• Dark-coloured urine
• Itching of the skin
• Lethargy or fatigue (unusual tiredness or weakness)
• Influenza-like syndrome (joint and muscle pain with fever)

If you experience 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 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 skin rash)
• Gastro-oesophageal reflux (acid reflux)
• Diarrhoea
• Nasal congestion
• Syncope (fainting)
• Palpitations (fast or irregular heartbeat)
• Low blood pressure

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

• Thrombocytopenia (low platelet count in the blood)
• Neutropenia/leucopenia (low white blood cell count)
• Changes in liver function tests associated with hepatitis (liver inflammation, including possible worsening of pre-existing hepatitis) and/or jaundice (yellowing of the skin or the whites of the eyes)

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

• Anaphylaxis (generalized allergic reaction), angioedema (swelling, most commonly around the eyes, lips, tongue or throat)
• Cirrhosis, liver failure (severe impairment of liver function), autoimmune hepatitis (liver inflammation caused by the body's immune system attacking liver cells), which may occur several months or even years after starting treatment.

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 have been the same as those reported 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.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 Mylan

Keep this medicine out of the sight and reach of children.
This medicine does not require any special storage conditions.
Do not use this medicine after the expiry date stated on the carton and blister after "Exp.". The expiry date refers to the last day of that month.
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 Mylan contains
The active substance is bosentan.
Each tablet contains 62.5 mg or 125 mg of bosentan (as monohydrate).
The other components are: maize starch, pregelatinized maize starch, sodium starch glycolate, povidone,
sodium lauryl sulfate, glycerol dibehenate and magnesium stearate. The film coating contains hypromellose
(E464), titanium dioxide (E171), triacetin, talc, yellow iron oxide (E172) and red iron oxide (E172).
Description of the appearance of Bosentan Mylan and pack contents
[62.5 mg] – Orange-white, round, biconvex, film-coated tablet with bevelled edges, marked with “M” on one side and “BNI” on the other side.
[125 mg] – Orange-white, oval, biconvex, film-coated tablet with bevelled edges, marked with “M” on one side and “BN2” on the other side.
The tablets are available in blisters in pack sizes of 14, 14 x 1 (unit dose blister), 28 x 1 (unit dose blister), 56, 56 x 1 (unit dose blister), 112, 112 x 1 (unit dose blister).
Not all pack sizes may be marketed.
Marketing Authorization Holder
Mylan S.p.A., Via Vittor Pisani 20, 20124 Milano
Responsible manufacturers for batch release
McDermott Laboratories Limited trading as Gerard Laboratories, 35/36 Baldoyle Industrial Estate, Grange Road, Dublin 13, Ireland.
Mylan Hungary Kft, Mylan útca 1, Komárom H-2900 Hungary.
Mylan Germany GmbH, Zweigniederlassung Bad Homburg v. d. Hoehe, Benzstrasse 1, Bad Homburg v. d. Hoehe, Hessen, 61352, Germany.
This medicinal product is authorized in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
France: Bosentan Viatris 62.5mg & 125mg comprimé pélliculé
Italy: Bosentan Mylan
Portugal: Bosentano Mylan
Spain: Bosentán MYLAN 62.5 mg & 125 mg comprimidos recubiertos con película EFG