Bosentan Dr. Reddy's 125 mg Film-Coated Tablets

• 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 only. 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 talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

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

• 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 cyclosporine A (a medicine used after a transplant or to treat psoriasis).

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

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 3 months after that, as patients taking bosentan may get anaemia.

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

Bosentan is not recommended in paediatric patients with systemic sclerosis and ongoing digital ulcer disease. Please see also section 3 ‘How to take 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:

• cyclosporine 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 (a medicine against fungal infections), ketoconazole (a medicine used to treat Cushing´s syndrome), or nevirapine (an HIV medicine) as these medicines are not recommended to be used together with bosentan
• other medicines for the treatment of HIV infection, 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
• other medicines for the treatment of pulmonary hypertension sildenafil and tadalafil
• warfarin (an anticoagulant agent)
• simvastatin (used to treat hypercholaesterolemia).

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, affect your vision and affect your ability to drive and use machines. Therefore, if you feel dizzy or that your vision is blurred while taking bosentan, do not drive or operate any tools or machines.

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

Bosentan passes into your breast milk. You are advised to stop breast-feeding if bosentan is prescribed for you, because it is not known if bosentan in breast milk can harm your baby. Talk to your doctor about this.

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.

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

Bosentan can be taken with or without food.

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 aged 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.

Please note that bosentan is also available as a dispersible 32 mg tablet formulation, which may make correct dosing easier for children and patients with low body weight or difficulties to swallow film-coated tablets.

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.

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

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

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.

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 get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

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

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

Common (may affect up to one 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 heart beats)
• low blood pressure
• nasal congestion

Uncommon (may affect up to one in 100 people)

• thrombocytopenia (low number of blood platelets)
• neutropenia/leukopenia (low number of white blood cells)
• 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) – if this occurs tell your doctor immediately

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

• anaphylaxis (general allergic reaction), angioedema (swelling, most commonly around the eyes, lips, tongue or throat)
• cirrhosis (scarring) of the liver, liver failure (serious disturbance of liver function)

Blurred vision have also been reported at an unknown frequency (frequency cannot be estimated from the available data).

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

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, Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

The active substance is bosentan as monohydrate. Each tablet contains 62.5 mg or 125 mg of bosentan (as monohydrate).

The other ingredients in the tablet core are maize starch, pre-gelatinised starch, sodium starch glycolate, povidone, glycerol dibehenate and magnesium stearate. The film coating contains hypromellose (E464), titanium dioxide (E171), triacetin, talc, ethylcellulose, cetyl alcohol, sodium lauryl sulfate, iron oxide yellow (E172) and iron oxide red (E172).

Bosentan 62.5 mg tablets are light orange, film-coated, round biconvex tablets (diameter 6 mm), debossed with “62.5” on one side and plain on the other side.

Bosentan 125 mg tablets are light orange, film-coated, oval biconvex tablets (dimensions 11 mm x 5 mm), debossed with “125” on one side and plain on the other side.

Bosentan 62.5 mg tablets are available in blister packs of 14, 56 or 112 tablets. Bosentan 125 mg tablets are available in blister packs of 28, 56, 60,112 or 120 (2 x 60) tablets.

Not all pack sizes may be marketed.