Bosentan Aurobindo

Package leaflet: Information for the user

Bosentan Aurobindo 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 or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

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

Bosentan Aurobindo tablets contain bosentan, which blocks a natural hormone called
endothelin-1 (ET-1) that causes narrowing of blood vessels. Bosentan Aurobindo therefore causes blood vessels to widen and belongs to a class of medicines known as “endothelin receptor antagonists”.
Bosentan Aurobindo 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 Aurobindo widens the pulmonary arteries, making it easier for the heart to pump blood through them; this leads to a reduction in blood pressure and an improvement in symptoms.

Bosentan Aurobindo is used to treat patients with pulmonary arterial hypertension (PAH) 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” indicates slight limitation in physical activity. The PAH for which Bosentan
Aurobindo 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 the fingers and toes) in adult patients with a condition called scleroderma. Bosentan Aurobindo reduces the number of new ulcers developing on the fingers and toes.

2. What you should know before taking Bosentan Aurobindo

Do not take Bosentan Aurobindo

• 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 Aurobindo”;
• 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
Talk to your doctor or pharmacist before taking Bosentan Aurobindo.
Tests required by your doctor before starting treatment with Bosentan Aurobindo

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

Abnormalities in liver function tests and anaemia (low haemoglobin) have been observed in some patients treated with Bosentan Aurobindo.
Tests your doctor will prescribe during treatment
During treatment with Bosentan Aurobindo, your doctor will regularly request blood tests to monitor any changes in liver function and haemoglobin levels.
For all these tests, also refer to the Patient Information Card (included in the Bosentan Aurobindo tablet pack). It is important that you undergo these blood tests at regular intervals throughout the entire period of Bosentan Aurobindo administration. It is recommended that you 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 the date of your next test.
Blood tests for liver function
These will be performed every month for the entire duration of treatment with Bosentan Aurobindo. 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 Aurobindo may develop anaemic conditions.
If these results are abnormal, your doctor may decide to reduce the dose or discontinue treatment with Bosentan Aurobindo and perform further tests to determine the cause.
Children and adolescents
Bosentan Aurobindo is not recommended in paediatric patients with systemic sclerosis and active digital ulcers. See also section 3. How to take Bosentan Aurobindo.
Other medicines and Bosentan Aurobindo
Inform your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including those purchased without 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 Aurobindo;
• sirolimus or tacrolimus, which are medicines used after transplants, the use of which together with Bosentan Aurobindo is not recommended;
• glibenclamide (a medicine for diabetes), rifampicin (a medicine for tuberculosis), fluconazole (a medicine for treating 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 Aurobindo is not recommended;
• other medicines for the treatment of HIV infection, which may require special monitoring if used together with Bosentan Aurobindo;
• hormonal contraceptives, which are not effective as a sole method of contraception when you are taking Bosentan Aurobindo. Inside the Bosentan Aurobindo tablet pack, you will find a Patient Information Card which you should read carefully. Your treating doctor 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 agent);
• simvastatin (used to treat hypercholesterolaemia).

Bosentan Aurobindo with food, drinks and alcohol
Bosentan Aurobindo may be taken with or without food.
Pregnancy, breast-feeding and fertility
Women of childbearing age
DO NOT take Bosentan Aurobindo if you are pregnant or planning to become pregnant.
Pregnancy test
Bosentan Aurobindo may harm the unborn child conceived before or during treatment. If you are a woman of childbearing age, your doctor will ask you to perform a pregnancy test before starting treatment with Bosentan Aurobindo and to repeat it regularly during treatment with Bosentan Aurobindo.
Contraceptives
If you are a woman of childbearing age, you must use a reliable method of birth control (contraception) while taking Bosentan Aurobindo. Your doctor or gynaecologist will advise you on reliable contraceptive methods during treatment with Bosentan Aurobindo. Since Bosentan Aurobindo 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 Aurobindo tablets, you will find a Patient Information Card. You should complete this card and bring it to your next doctor's 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 Aurobindo if you are of childbearing age.
Inform your doctor immediately if you become pregnant during treatment with Bosentan Aurobindo or if you plan to become pregnant in the near future.
Breast-feeding
Bosentan Aurobindo passes into breast milk. It is recommended that you stop breast-feeding if Bosentan Aurobindo is prescribed, as it may harm your baby. Talk to your doctor if you have any questions about this.
Fertility
If you are a man taking Bosentan Aurobindo, this medicine may reduce sperm count. It cannot be ruled out that this could impair your ability to father a child. Talk to your doctor if you have any questions about this.
Driving and using machines
Bosentan Aurobindo has no or negligible influence on the ability to drive and use machines. However, Bosentan Aurobindo may cause hypotension (lowering of your blood pressure), which may cause dizziness, affect your vision and impact your ability to drive and use machines. Therefore, if you experience dizziness or blurred vision during treatment with Bosentan Aurobindo, do not drive or operate tools or machinery.

3. How to take Bosentan Aurobindo

Treatment with Bosentan Aurobindo should 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. If you have any doubts, consult your doctor or pharmacist.

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. Afterwards, your doctor will usually recommend increasing to one 125 mg tablet twice daily, depending on your response to Bosentan Aurobindo.

Children and adolescents
The recommended dose for children applies only to PAH. For children aged 1 year and older, treatment with Bosentan Aurobindo usually starts at a dose of 2 mg per kg body weight taken twice daily (morning and evening). Your doctor will advise you on the appropriate dose.

Please note that bosentan is also available in other formulations, which may allow more accurate dosing for children and for patients with low body weight or difficulty swallowing film-coated tablets.

If you feel that the effect of Bosentan Aurobindo is too strong or too weak, discuss this with your doctor to determine whether your dose should be adjusted.

How to take Bosentan Aurobindo
Take the tablets (morning and evening) with water. The tablets may be taken with or without food.

If you take more Bosentan Aurobindo than you should
If you have taken more tablets than prescribed, contact your doctor immediately.

If you forget to take Bosentan Aurobindo
If you forget to take a dose, 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 the missed tablet.

If you stop taking Bosentan Aurobindo
Stopping treatment with Bosentan Aurobindo abruptly may lead to worsening of symptoms. Do not discontinue treatment unless instructed by your doctor. Your doctor may advise you to gradually reduce the dose over several days before stopping 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 everybody gets them.
The most serious side effects associated with bosentan are:

• impaired liver function, which may affect more than 1 in 10 people;
• anaemia (reduced blood test values), which may affect 1 in 10 people. Anaemia occasionally requires a blood transfusion. Blood and liver function tests must be monitored during treatment with bosentan (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 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 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 legs and ankles or other signs due to fluid retention).

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

• flushed appearance or redness of the skin;
• hypersensitivity reactions (including skin inflammation, itching, and skin 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 platelet count in the blood);
• neutropenia/leucopenia (low white blood cell count);
• abnormalities 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 eyes, lips, tongue or throat);
• liver cirrhosis (scarring), severe liver failure (serious 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.

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 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.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 Aurobindo

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 carton and blister after EXP. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
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 Aurobindo contains

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

The other components are:
Tablet core: pregelatinized starch, maize starch, sodium starch glycolate (type A),
crospovidone (type B), povidone (K-90), glyceryl dibehenate, and magnesium stearate.
Coating: hypromellose (E464), ethylcellulose, triacetin, talc, titanium dioxide (E171), iron oxide
yellow, iron oxide red.

Description of the appearance of Bosentan Aurobindo and package contents
Film-coated tablets.
Bosentan Aurobindo 62.5 mg film-coated tablets
Orange-white, round [diameter: 6.1 mm], biconvex, film-coated tablet, printed with “K” on one side and “21” on the other.
Bosentan Aurobindo 125 mg film-coated tablets
Orange-white, oval, biconvex, film-coated tablet, printed with “K” on one side and “22” on the other, separated by a break line. The tablet can be divided into equal doses. Dimensions: 11.2 mm x 5.2 mm.
Bosentan Aurobindo film-coated tablets are available in PVC/PE/PVdC triple-laminated opaque white blister packs with aluminum foil and in HDPE bottles with polypropylene caps.
Blister pack:
For 62.5 mg: 14, 28, 30, 50, 56, 60, 90, 98 and 112 film-coated tablets.
For 125 mg: 10, 14, 28, 30, 50, 56, 60, 90, 98, 100, 120 and 112 film-coated tablets.
Bottle:
30, 100 and 1000 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Aurobindo Pharma (Italia) S.r.l. – Via San Giuseppe, 102 – 21047 Saronno (VA), Italy

Manufacturer
APL Swift Services (Malta) Limited - HF26, Hal Far Industrial Estate, Hal Far, Birzebbugia, BBG – 3000, Malta
Orion Corporation - Orion Pharma, Orionintie 1 - FI-02200 Espoo, Finland

This medicinal product is authorized in the Member States of the European Economic Area under the following names:
Cyprus: Bosentan Aurobindo 62.5 mg/125 mg film-coated tablets
France: Bosentan Arrow 62.5 mg, film-coated tablet
Bosentan Arrow 125 mg, scored film-coated tablet
Germany: Bosentan Puren 62.5 mg/125 mg film tablets
Italy: Bosentan Aurobindo
Netherlands: Bosentan Aurobindo 62.5 mg/125 mg, film-coated tablets
Portugal: Bosentan Aurobindo
Spain: Bosentán Aurovitas 62.5 mg/125 mg film-coated tablets EFG