PACKAGE LEAFLET: INFORMATION FOR THE USER

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

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 further questions, ask your doctor or pharmacist

•    This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

•    If you get any side effects, gets serious, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet:

1.    What bosentan is and what it is used for

2.    What you need to know before you take bosentan

3.    How to take bosentan

4.    Possible side effects

5.    How to store bosentan

6.    Contents of the pack and other information

. WHAT BOSENTAN IS AND WHAT IT IS USED FOR

The name of your medicine is Bosentan 62.5 mg film-coated tablets or Bosentan 125 mg film-coated tablets (called bosentan throughout this leaflet).

Bosentan tablets contain bosentan, which blocks a naturally occurring hormone called endothelin-1 (ET-1), which causes blood vessels to narrow. Bosentan therefore causes blood vessels to expand and belongs to the class of medicines called “endothelin receptor antagonists”.

Bosentan is used to treat:

-    Pulmonary arterial hypertension (PAH): PAH is a disease of severe narrowing of the blood vessels in the lungs resulting in high blood pressure in the blood vessels (the pulmonary arteries) that carry blood from the heart to the lungs. This pressure reduces the amount of oxygen that can get into the blood in the lungs, making physical activity more difficult. Bosentan widens the pulmonary arteries, making it easier for the heart to pump blood through them. This lowers the blood pressure and relieves the symptoms.

Bosentan is used to treat patients with class III pulmonary arterial hypertension (PAH) to improve exercise capacity (the ability to carry out physical activity) and symptoms. The “class” reflects the seriousness of the disease: “class III” involves marked limitation of physical activity. Some improvements have also been shown in patients with class II PAH. “Class II” involves slight limitation of physical activity. The PAH for which bosentan is indicated can be:

-    primary (with no identified cause or familial).

-    caused by scleroderma (also called systemic sclerosis, a disease where there is abnormal growth of the connective tissue that supports the skin and other organs).

caused by congenital (inborn) heart defects with shunts (abnormal passageways) causing abnormal flow of blood through the heart and lungs.

2. WHAT YOU NEED TO KNOW BEFORE YOU TAKE BOSENTAN

Do not take bosentan

•    if you are allergic to bosentan or any of the other ingredients of this medicine (listed in section 6).

•    if you have liver problems (ask your doctor).

•    if you are pregnant, or could get pregnant because you are not using reliable contraceptive methods. Please read the information under "Contraceptives" and "Other medicines and bosentan”.

•    if you are taking cyclosporin A (a medicine used after a transplant or to treat psoriasis).

If any of these apply to you, tell your doctor.

Warnings and precautions

Tests your doctor will do 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 child-bearing potential.

Some patients taking bosentan have been found to have abnormal liver function tests and anaemia (low haemoglobin).

Tests your doctor will do during treatment

During treatment with bosentan, your doctor will arrange for regular blood tests to check for changes in your liver function and haemoglobin level.

For all these tests please refer also to the Patient Alert Card (inside your pack of bosentan tablets). It is important that you have these regular blood tests as long as you are taking bosentan. We suggest you write the date of your most recent test and also of your next test (ask your doctor for the date) on the Patient Alert Card, to help you remember when your next test is due.

Blood tests for liver function

These will be done every month for the duration of treatment with bosentan. After an increase in dose an additional test will be done after 2 weeks.

Blood tests for anaemia

These will be done every month for the first 4 months of treatment, then every that, as patients taking bosentan may get anaemia.

If these results are abnormal, your doctor may decide to reduce your dose or with bosentan and to perform further tests to investigate the cause.

Other medicines and bosentan

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

-    Cyclosporin A (a medicine used after transplants and to treat psoriasis), which must not be used together with bosentan

-    Sirolimus or tacrolimus, which are medicines used after transplants, as these are not recommended to be used together with bosentan

-    Glibenclamide (a diabetes medicine), rifampicin (a tuberculosis medicine), fluconazole or ketoconazole (medicines against fungal infections), nevirapine (an HIV medicine) as these medicines are not recommended to be used together with bosentan

-    Other medicines for the treatment of HIV infection such as lopinavir and ritonavir, which may require special monitoring if used together with bosentan

-    Hormonal contraceptives, which are not effective as the sole method of contraception when you take bosentan. Inside your pack of bosentan tablets you will find a Patient Alert Card which you should read carefully. Your doctor and/or gynaecologist will establish the contraception which is appropriate for you.

-    Warfarin (a medicine used to prevent blood clotting), which requires more frequent monitoring if used together with bosentan

-    Sildenafil (a medicine used to treat erectile dysfunction and pulmonary arterial hypertension), which requires caution when used with bosentan

-    Simvastatin (a medicine used to decrease elevated lipid levels in blood), which may require monitoring of cholesterol levels and a dose adjustment if it’s necessary.

Driving and using machines

Bosentan has no or negligible influence on the ability to drive and use machines. However,

bosentan can induce hypotension (decrease of your blood pressure) which can make you feel

dizzy and affect your ability to drive and use machines. Therefore, if you feel dizzy while

taking bosentan, do not drive or operate any tools or machines.

Bosentan with food and drink

Bosentan can be taken with or without food.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking bosentan.

Women of child-bearing age

Do NOT take bosentan if you are pregnant or planning to become pregnant.

Pregnancy tests

Bosentan may harm unborn babies conceived before starting or during treatment. If you are a woman who could become pregnant, your doctor will ask you to take a pregnancy test before you start taking bosentan, and regularly while you are taking bosentan.

Contraceptives

If it is possible that you could become pregnant, use a reliable form of birth control (contraception) while you are taking bosentan. Your doctor or gynaecologist will advise you about reliable contraceptive methods while taking bosentan. Because bosentan may make hormonal contraception (e.g., oral, injection, implant, or skin patches) ineffective, this method on its own 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 also use a condom). Inside your pack of bosentan tablets you will find a Patient

Alert Card. You should complete this card and take 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. Monthly pregnancy tests are recommended while you are taking bosentan and are of child-bearing age.

Tell your doctor immediately if you become pregnant while you are taking bosentan, or plan to become pregnant in the near future.

Breast-feeding

Tell your doctor immediately if you are breast-feeding. You are advised to stop breastfeeding if bosentan is prescribed for you, because it is not known whether this medicine passes into breast milk.

Fertility

If you are a man taking bosentan, it is possible that this medicine may lower your sperm count. It cannot be excluded that this may affect your ability to father a child. Talk to your doctor if you have any questions or concerns about this.

3. HOW TO TAKE BOSENTAN

Treatment with bosentan should only be started and monitored by a doctor who has experience in the treatment of PAH. Always take this medicine exactly as your doctor has told you.

Check with your doctor or pharmacist if you are not sure.

Recommended dose Adult

The treatment in adults is usually started for the first 4 weeks with 62.5 mg twice daily (morning and evening), from then your doctor will usually advise you to take a 125 mg tablet twice daily, depending on how you react to bosentan.

Children and adolescents

The dose recommendation in children is only for PAH. For children 1 year and older, treatment with bosentan is usually started with 2 mg per kg bodyweight twice daily (morning and evening). Your doctor will advise you on your dosing.

Bosentan should not be administered to children with a body weight below 31 kg, and an alternative product containing bosentan should be used.

If you have the impression that the effect of bosentan is too strong or too weak, talk to your doctor in order to find out whether your dose needs to be changed.

How to take bosentan

Tablets should be taken (morning and evening), swallowed with water. The tablets can be taken with or without food.

If you take more bosentan than you should

If you take more tablets than you have been told to take, contact your doctor immediately.

If you forget to take bosentan

If you forget to take bosentan, take a dose as soon as you remember, then continue to take your tablets at the usual times. Do not take a double dose to make up for forgotten tablets.

If you stop taking bosentan

Suddenly stopping your treatment with bosentan may lead to your symptoms getting worse. Do not stop taking bosentan unless your doctor tells you to. Your doctor may tell you to reduce the dose over a few days before stopping completely.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist

. 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:

•    Abnormal liver function which may affect more than 1 in 10 people.

•    Allergic (hypersensitivity) reaction with signs such as itching, rash or swelling of the hands, feet, ankles, face, lips or throat which may cause difficulty in swallowing or breathing. May affect up to 1 in 10 people.

•    Anaemia (low blood value) with signs as pale skin and weakness or breathlessness which may affect up to 1 in 10 people. Anaemia may occasionally require blood transfusion.

•    Changes in blood cells (platelets and white blood cells) with signs of infection, unexplained bruising or bleeding which may affect up to 1 in 100 people.

•    Anaphylaxis (serious allergic reaction) which causes difficulty in breathing or dizziness may affect up to 1 in 1,000 people.

•    Serious disturbances of liver function which may affect up to 1 in 1,000 people.

Signs that your liver may not be working properly include:

•    nausea (urge to vomit).

•    vomiting.

•    fever (high temperature).

•    pain in your stomach (abdomen).

•    jaundice (yellowing of your skin or the whites of your eyes).

•    dark-coloured urine.

•    itching of your skin.

•    lethargy or fatigue (unusual tiredness or exhaustion).

•    flu-like syndrome (joint and muscle pain with fever).

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

Your liver and blood values will be monitored during treatment with bosentan (see section 2). It is important that you have these tests as ordered by your doctor.

Other side effects:

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

•    Headache.

•    Oedema (swelling of the legs and ankles or other signs of fluid retention).

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

•    Flushed appearance or redness of skin.

•    Hypersensitivity reactions (including skin inflammation, itching and rash).

•    Gastrooesophageal reflux disease (acid reflux).

•    Diarrhoea.

•    Syncope (fainting).

•    Palpitations (fast or irregular heartbeats).

•    Low blood pressure.

•    Nasal congestion.

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

•    Elevated liver function tests with hepatitis (inflammation of the liver) including possible exacerbation of underlying hepatitis and/or jaundice (yellowing of the skin or the whites of the eyes).

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

•    Angioedema (swelling, most commonly around the eyes, lips, tongue or throat).

•    Cirrhosis (scarring) of the liver.

Side effects in children and adolescents

The side effects that have been reported in children treated with bosentan are the same as those in adults.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow card Scheme at www.mhra.gov.uk/yellowcard.

By reporting side effects you can help provide more information on the safety of this medicine.

5. HOW TO STORE BOSENTAN

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the package. The expiry date refers to the last day of that month.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. CONTENTS OF THE PACK AND OTHER INFORMATION

What Bosentan film-coated tablets contains

The active substance is bosentan.

Each 62.5 mg tablet contains 62.5 mg of bosentan (as monohydrate). Each 125 mg tablet contains 125 mg of bosentan (as monohydrate).

The other ingredients are maize starch, povidone (K-30), sodium starch glycolate (type B), pregelatinized maize starch, glycerol dibehenate, magnesium stearate, opadry II 85F230061 orange (a mixture consisting of polyvinyl alcohol, titanium dioxide, macrogol 3350, talc , iron oxide yellow (E 172) and iron oxide red (E 172)).

What Bosentan film-coated tablets look like and contents of the pack

Bosentan 62.5 mg film-coated tablets are round, biconvex-shaped, light orange coloured

film-coated tablets with the diameter approx. 6.1 mm.

Bosentan 125 mg film-coated tablets are oval, biconvex-shaped, light orange coloured film-coated tablets with length approx. 11.1 mm and width approx. 5.1 mm.

Size of packing: 14, 56 and 112 film-coated tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Zentiva, One Onslow Street, Guildford, Surrey, GU1 4YS, UK.

Manufacturer

Zentiva, k.s., U kabelovny 130, 102 37 Praha, Dolni Mecholupy, Czech Republic This leaflet was last updated in January 2016