Leaflet: information for the user

Bosentan Cipla 62.5 mg film-coated tablets

Read this leaflet carefully before you start taking this medicine, because it contains important information for you.

- Keep this leaflet, as 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 they have the same symptoms as you, as it may harm them.

- If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4

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

2. What you need to know before you start taking Bosentan Cipla

3. How to take Bosentan Cipla

4. Possible side effects

5. Storage of Bosentan Cipla

6. Contents of the pack and additional information

Bosentan Cipla contains bosentan, which blocks the natural hormone called endothelin-1 (ET-1), and causes constriction of blood vessels. Bosentan Cipla therefore causes dilation of blood vessels and belongs to the class of medications known as "endothelin receptor antagonists".

Bosentan Cipla is used to treat:

•Pulmonary arterial hypertension (PAH):PAH is a severe narrowing of the blood vessels in the lungs, resulting in an increase in blood pressure in the blood vessels (pulmonary arteries) that carry blood from the heart to the lungs. This pressure reduces the amount of oxygen that can reach the blood in the lungs, making physical activity more difficult. Bosentan Cipla widens the pulmonary arteries, making it easier for the heart to pump blood through them. This reduces blood pressure and alleviates symptoms.

Bosentan Cipla is used to treat patients with PAH in class III to improve symptoms and exercise capacity (the ability to perform physical activity). The "class" reflects the severity of the disease: 'class III' implies a marked limitation of physical activity. Some improvements have been observed in patients with PAH class II. Class II implies a slight limitation of physical activity. PAH for which Bosentan Cipla is indicated may be:

•primary (in which the cause or hereditary is not identified),

•caused by scleroderma (also known as systemic sclerosis, a disease in whichthere is abnormal growth of connective tissue that forms the support of the skin and otherorgans),

•caused by congenital heart defects (at birth) with abnormal communications

(abnormal flow of blood between the heart and lungs).

•Digital ulcers(ulcers on the fingers of the hands and feet) in adult patients who

suffer from a disease called scleroderma. Bosentan Cipla reduces the number of new digital ulcers (on hands and feet) that appear.

Do not take Bosentan Cipla:

•if you are allergic to bosentanor to 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 be pregnantwithout using reliable contraceptive methods. Please read the information in the section “Contraceptives” and “Other medicines and Bosentan Cipla”

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

If you have any of these conditions, inform your doctor.

Warnings and precautions

Consult your doctor or pharmacist before taking Bosentan Cipla

Tests that your doctor will perform before prescribing the treatment

• a blood test to assess liver function

• a blood test to detect anemia (low hemoglobin)

• a pregnancy test if you are a fertile woman

Abnormalities in liver function tests and anemia have been found in some patients taking Bosentan Cipla.

Tests that your doctor will perform during treatment

During treatment with Bosentan Cipla, your doctor will schedule regular blood tests to monitor changes in your liver function and hemoglobin levels.

Please refer to the Patient Alert Card (inside the Bosentan Cipla packaging). It is essential to perform regular blood tests while taking Bosentan Cipla. We recommend that you write the date of the most recent test and your next test (ask your doctor for the date) on the Patient Alert Card to help you remember when your next visit is.

Liver function tests

These tests must be performed monthly throughout the duration of treatment with Bosentan Cipla. After a dose increase, an additional test should be performed after 2 weeks.

Anemia tests

These tests will be performed monthly for the first 4 months of treatment and then every 3 months, as patients taking bosentan may develop anemia.

If these tests show abnormalities, your doctor may decide to reduce the dose or discontinue treatment with bosentan and perform additional tests to investigate the cause.

Children and adolescents

Bosentan Cipla is not recommended for pediatric patients with systemic sclerosis and active digital ulceration. Bosentan Cipla should not be used in children with a body weight less than 31 kg with pulmonary arterial hypertension. See also section 3. How to take Bosentan Cipla.

Taking Bosentan Cipla with other medicines

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

• ciclosporin A (a medicine administered after transplants and to treat psoriasis) which should not be administered with bosentan.

• sirolimus or tacrolimus, which are medicines administered after transplants, and it is not recommended to administer them with bosentan.

• glibenclamide (a diabetes medicine), rifampicin (a tuberculosis medicine), fluconazole (an antifungal medicine), ketoconazole (a medicine used to treat Cushing's syndrome), or nevirapine (an HIV medicine) as it is not recommended to administer these medicines with bosentan.

• other medicines for the treatment of HIV infection, which administered with Bosentan Cipla may require special monitoring.

• hormonal contraceptives, which are not effective as the sole method of contraception when taking bosentan. Inside the Bosentan Cipla packaging, you will find a Patient Alert Card that you should read carefully. Your doctor and/or gynecologist will establish an alternative or additional reliable contraceptive method for you.

• other medicines for the treatment of pulmonary arterial hypertension: sildenafil and tadalafil.
• Warfarin (an anticoagulant).
• Simvastatin (used to treat hypercholesterolemia).

Taking Bosentan Cipla with food

Bosentan Cipla can be taken with or without food

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before taking this medicine.

Fertile women

DO NOT take Bosentan Cipla if you are pregnant or plan to become pregnant.

Pregnancy tests

Bosentan may affect unborn babies conceived before or during treatment. If you are a fertile woman, your doctor will ask you to perform a pregnancy test before starting treatment with bosentan, and regularly while taking Bosentan Cipla.

Contraceptives

If you may become pregnant, use a reliable contraceptive method while taking bosentan. Your doctor or gynecologist will advise you on reliable contraceptive methods while taking bosentan. Since bosentan may make hormonal contraceptives ineffective (e.g., oral, injection, implant, or skin patch), this method alone is not reliable. Therefore, if you use hormonal contraceptives, you must also use a barrier method (e.g., female condom, diaphragm, spermicide, or your partner must also use a condom). Inside the Bosentan Cipla packaging, you will find a Patient Alert Card. Please complete this card and bring it to your doctor's next visit so that your doctor or gynecologist can determine if you need an alternative or additional reliable contraceptive method. It is recommended to perform a pregnancy test monthly while taking bosentan and are fertile.

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

Breastfeeding

Inform your doctor

Fertility

If you are a man taking bosentan, it is possible that this medicine may reduce your sperm count. It cannot be ruled out that it may affect your ability to father a child. Discuss any concerns or doubts with your doctor.

Driving and operating machinery

Bosentan has no influence or has a negligible influence on driving and operating machinery. However, bosentan may induce hypotension (low blood pressure) that may cause dizziness, affect your vision, and affect your ability to drive and operate machinery. Therefore, if you feel dizzy or have blurred vision while taking bosentan, do not drive or operate tools or machinery.

Bosentan Cipla contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per tablet; it is essentially “sodium-free”.

The treatment with bosentan should only be initiated and monitored by a doctor with experience in the treatment of HAP or systemic sclerosis.

Follow exactly the administration instructions of this medication indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

The recommended dose is:

Adults:

Treatment in adults usually starts with 62.5 mg twice a day (morning and night) for the first 4 weeks, after which your doctor will normally advise you to take one 125 mg tablet twice a day, depending on how you react to Bosentan Cipla.

Use in children and adolescents

The recommended dose in children is only for HAP. For children over 1 year of age, treatment with bosentan usually starts with 2 mg per kg of body weight twice a day (morning and night). Your doctor will advise you on the dose; however, some dosages are not possible in children with a body weight of less than 31 kg. For such patients, the lower-dose Bosentan tablet is needed. Your doctor will advise you on your dosage.

Please remember that bosentan is also available in dispersible tablets of 32 mg, which may facilitate dosing in children and patients with low weight or difficulties swallowing coated tablets.

If you feel that the effect of bosentan is too strong or too weak, consult your doctor to verify if you need a dose adjustment.

How to take Bosentan Cipla

The tablets should be taken (morning and night) with water. The tablets can be taken with or without food.

If you take more Bosentan Cipla than you should

If you take more tablets than you should, consult your doctor immediately.

In case of overdose or additional intake, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone 915620420, indicating the medication and the amount ingested.

If you forget to take Bosentan Cipla

If you forget to take bosentan, take the dose as soon as you remember and then continue taking it at your usual time. Do not take a double dose to compensate for the missed doses.

If you interrupt treatment with Bosentan Cipla

If you suddenly stop treatment with bosentan, your symptoms may worsen. Do not stop taking Bosentan Cipla unless your doctor tells you to. Your doctor may advise you to reduce the dose over a few days before stopping it completely.

If you have any other doubts about the use of this medication, ask your doctor or pharmacist.

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

The most serious side effects with Bosentan Cipla are:

• Abnormal liver function that can affect more than 1 in 10 people

• Anemia (decreased blood count) that can affect more than 1 in 10 people. Anemia may occasionally require blood transfusions.

Your liver and blood values will be analyzed during treatment with Bosentan Cipla (see section 2). It is essential to have these analyses done as prescribed by your doctor.

The signs that your liver may not be functioning correctly include:

• Nausea (need to vomit)

• Vomiting

• Fever (elevated temperature)

• Abdominal pain (stomach pain)

• Icterus (yellowish discoloration of the skin or white of the eyes)

• Dark-colored urine

• Itching (pruritus)

• Lethargy or fatigue (unusual or excessive tiredness)

• Pseudo-gripal syndrome (joint and muscle pain with fever)

If you experience any of these symptoms, consult your doctor immediately.

Other side effects:

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

• Headache

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

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

• Rubefaction (skin redness)

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

• Gastroesophageal reflux (acid reflux)

• Diarrhea

• Syncope (fainting)

• Palpitations (rapid or irregular heartbeats)

• Low blood pressure

• Nasal congestion

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

• Thrombocytopenia (decreased platelet count in the blood)

• Neutropenia/leucopenia (decreased white blood cell count)

• Elevated liver function tests with hepatitis (inflammation of the liver) including possible exacerbation of hepatitis and/or icterus (yellowish discoloration of the skin or white of the eyes)

Rare (can affect up to 1 in 1000 people):

• Anaphylaxis (generalized allergic reaction), angioedema (swelling, often around the eyes, lips, tongue, or throat)

• Cirrhosis (fibrosis) of the liver, liver failure (severe alteration of liver function)

Unknown (frequency cannot be estimated from available data):

• Blurred vision

Other side effects in children and adolescents:

The side effects observed in children treated with Bosentan Cipla are the same as in adults.

Reporting of side effects:

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect not listed in this prospectus. You can also report them directly through the Spanish System of Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the box and on the blister after “CAD”. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Medications should not be disposed of through drains or in the trash. Dispose of the packaging and medications you no longer need at the SIGRE collection point of the pharmacy or any other medication collection system. If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition of Bosentan Cipla

The active ingredient is bosentan

-Bosentan Cipla62.5 mg film-coated tablets:

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

The other components are:

• Core tablet:Maize starch, sodium starch glycolate (type B), povidone K-30, pregelatinized maize starch, dibehenate of glycerol and magnesium stearate.
• Film-coating:Hydroxypropylmethylcellulose, titanium dioxide (E171), triacetin, talc, iron oxide yellow (E172) and iron oxide red (E172), ethylcellulose, cetomacrogol and sodium lauryl sulfate.

Appearance of the product and contents of the pack

Bosentan Cipla 62.5 mg film-coated tablets: round, biconvex, cream to light yellow coloured tablets, marked with "62.5" on one face and plain on the other face. Diameter 6.10±0.20mm.

PVC/PE/PVDC aluminium blisters containing 14, 56 and 112 film-coated tablets.

Single-dose perforated blisters: PVC/PE/PVDC aluminium blisters containing 14x1, 56x1 and 112x1 film-coated tablets.

Not all pack sizes may be marketed.

Marketing authorisation holder and manufacturer:

Marketing authorisation holder

Cipla Europe NV

De Keyserlei 58-60, Box-19,

2018 Antwerp, Belgium

Manufacturer

Cipla Europe NV

De Keyserlei 58-60 Box 19

2018 Antwerp, Belgium

S&D Pharma CZ, spol. s.r.o

Theodor 28, 273 08 Pchery, (Pharmos a.s. facility)

Czech Republic

Local representative

Cipla Europe NV subsidiary in Spain

C/Guzmán el Bueno, 133 Edificio Britannia

28003 Madrid

Phone 91 534 1673

This medicinal product is authorised in the Member States of the European Economic Area under the following names:

Last revision date of this leaflet: September 2019

For detailed and updated information on this medicinal product, please consult the website of the Spanish Agency of Medicines and Medical Devices (AEMPS):http://www.aemps.gob.es