Bosentan Teva

Package leaflet: Information for the user

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

Generic medicine
Please 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 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 yours, because it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

What is in this leaflet

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

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

Bosentan Teva tablets contain bosentan, which blocks a hormone naturally present in the body called endothelin-1 (ET-1), responsible for narrowing of blood vessels. Bosentan Teva therefore causes dilation of blood vessels and belongs to a class of medicines known as "endothelin receptor antagonists".

Bosentan Teva 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 pulmonary blood, making physical activity more difficult. Bosentan Teva 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 alleviation of symptoms.

Bosentan Teva 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" indicates a marked limitation in physical activity. Some benefits have also been observed in patients with PAH in class II. "Class II" involves less limitation in physical activity. The PAH for which Bosentan Teva is indicated may be:

• idiopathic (without identifiable or familial cause);

• 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 fingers and toes) in adult patients with a condition called scleroderma. Bosentan Teva reduces the number of new finger and toe ulcers.

2. What you need to know before taking Bosentan Teva

Do not take Bosentan Teva

• 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. Read the information provided under “Contraceptives” and “Other medicines and Bosentan Teva”
• if you are being treated with cyclosporine A (a medicine used after organ transplant or for the treatment of psoriasis).

If you are in any of these conditions, inform your doctor.
Warnings and precautions
Examinations required by your doctor before treatment

• a blood test to check your liver function
• a blood test to check for possible anemia (low hemoglobin)
• a pregnancy test if you are a woman of childbearing potential. In some patients treated with Bosentan Teva, abnormal liver function tests and anemia (low hemoglobin) have been observed.

Examinations your doctor will prescribe during treatment
During treatment with Bosentan Teva, your doctor will regularly request blood tests to monitor any changes in liver function and hemoglobin levels.
For all these tests, refer also to the Patient Information Card (included in the Bosentan Teva tablet packaging). It is important that you undergo these blood tests at regular intervals throughout the entire period of taking Bosentan Teva. 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 you do not forget the date of your next test.
Liver function blood tests
These will be performed every month for the entire duration of treatment with Bosentan Teva. After a dose increase, an additional test will be performed after 2 weeks.
Blood tests for anemia
These will be performed every month for the first 4 months of treatment and then every 3 months, as patients taking Bosentan Teva may develop anemia.
If these results are abnormal, your doctor may decide to reduce the dose or discontinue treatment with Bosentan Teva and perform further tests to determine the cause.
Children and adolescents
Bosentan Teva is NOT recommended in pediatric patients with systemic sclerosis and active digital ulcers. See also section 3 How to take Bosentan Teva.
Other medicines and Bosentan Teva
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those not requiring a prescription. It is particularly important that you 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 Teva
• sirolimus or tacrolimus, which are medicines used after transplants, and whose use together with Bosentan Teva is not recommended
• glibenclamide (a medicine for diabetes), rifampicin (a medicine for tuberculosis), fluconazole (a medicine for 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 Teva is not recommended
• other medicines for HIV infection, which may require special monitoring when used together with Bosentan Teva
• hormonal contraceptives, which are not effective as the sole method of contraception when you are taking Bosentan Teva. Inside the Bosentan Teva tablet packaging, you will find a Patient Information Card that you must read carefully. Your doctor and/or gynecologist will advise you on the appropriate contraceptive method for you
• other medicines for pulmonary hypertension: sildenafil and tadalafil
• warfarin (an anticoagulant)
• simvastatin (used to treat hypercholesterolemia)

Women of childbearing potential
DO NOT take Bosentan Teva if you are pregnant or planning a pregnancy.
Pregnancy test
Bosentan Teva may harm the unborn child conceived before or during treatment. If you are a woman of childbearing potential, your doctor will ask you to take a pregnancy test before starting Bosentan Teva and then regularly during treatment with Bosentan Teva.
Contraceptives
If you are a woman of childbearing potential, use a reliable method of birth control (contraception) while taking Bosentan Teva. Your doctor or gynecologist will advise you on reliable contraceptive methods during treatment with Bosentan Teva. Since Bosentan Teva may render hormonal contraception ineffective (e.g., oral and injectable contraceptives, implants, 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 condom). Inside the Bosentan Teva tablet packaging, you will find a Patient Information Card. You must complete it and bring it to your doctor at your next visit, so that your doctor or gynecologist can assess whether you need additional or alternative reliable contraceptive methods. During treatment with Bosentan Teva, and if you are of childbearing potential, it is recommended to perform a pregnancy test every month.
Inform your doctor immediately if you become pregnant during treatment with Bosentan Teva, or if you are planning to become pregnant in the near future.
Breast-feeding
Bosentan Teva is excreted in breast milk. It is recommended to DISCONTINUE breast-feeding if you are prescribed Bosentan Teva, as it is not known whether Bosentan Teva in breast milk could harm the infant. Consult a doctor.
Fertility
If you are a man being treated with Bosentan Teva, this medicine may reduce sperm count. It cannot be excluded that this may affect the ability to father a child. Consult your doctor for any questions or concerns regarding this issue.
Driving and use of machines
Bosentan Teva does not affect or has a negligible effect on the ability to drive or use machines. However, Bosentan Teva may cause hypotension (lowered blood pressure), which may cause dizziness, affect vision, and influence your ability to drive or use machines. Therefore, if you experience dizziness or blurred vision during treatment with Bosentan Teva, DO NOT drive and DO NOT use tools or machines of any kind.
Bosentan Teva contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per film-coated tablet, i.e. essentially ‘sodium-free’.

3. How to take Bosentan Teva

Treatment with Bosentan Teva 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. If you have any doubts, consult your doctor or pharmacist.
Bosentan Teva with food and drink
Bosentan Teva may be taken on an empty stomach or with food.
Recommended dose
Adults
In adults, treatment usually starts with one 62.5 mg tablet twice daily (morning and evening) for the first 4 weeks; thereafter, your doctor will usually recommend increasing to one 125 mg tablet twice daily, depending on your response to Bosentan Teva.
Children and adolescents
The recommended dose in children applies only to PAH. For children aged 1 year and older, treatment with bosentan usually starts at 2 mg per kg body weight twice daily (morning and evening). Your doctor will advise you on the correct dosage.
Please note that bosentan is also available in a dispersible tablet formulation of 32 mg, which allows easier administration of the correct dose in children, patients with low body weight, or patients who have difficulty swallowing film-coated tablets.
If you think that the effect of Bosentan Teva is too strong or too weak, contact your doctor to evaluate whether a dose adjustment is necessary.
How to take Bosentan Teva
Take the tablets (morning and evening) with water. The tablets may be taken on an empty stomach or with food.
If you take more Bosentan Teva than you should
If you take more tablets than prescribed, contact your doctor immediately.
If you forget to take Bosentan Teva
If you forget to take Bosentan Teva, take one 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 forgotten tablet.
If you stop taking Bosentan Teva
Suddenly stopping treatment with Bosentan Teva may lead to worsening of symptoms. DO NOT stop taking Bosentan Teva unless your doctor tells you to. Your doctor may instruct you to gradually reduce the dose a few days before completely stopping treatment.
If you have further 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 associated with bosentan are:

• liver function abnormalities, which may affect more than 1 in 10 people
• anaemia (reduction in blood test values), which may affect up to 1 in 10 people. Anaemia may occasionally require a blood transfusion. Your blood and liver test values will be monitored during treatment with Bosentan Teva (see section 2). It is important that you undergo these checks as prescribed by your doctor.

Signs of impaired 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)

Contact your doctor immediately if you notice any of these symptoms.
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 rash)
• gastroesophageal reflux disease (acid reflux)
• diarrhoea
• syncope (fainting)
• palpitations (rapid or irregular heartbeat)
• low blood pressure
• nasal congestion

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

• thrombocytopenia (low number of platelets in the blood)
• neutropenia/leucopenia (low number of white blood cells in the blood)
• increased liver function test values, 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 the eyes, lips, tongue or throat)
• liver cirrhosis (scarring), 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 Teva are the same as those reported in adults.
Reporting of side effects
If you experience any side effects, 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 Teva

Keep this medicine out of the sight and reach of children.
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.
Store below 30°C.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer used. This will help protect the environment.

6. Package contents and other information

What Bosentan Teva contains

• The active substance is bosentan.
  • Each film-coated tablet contains 62.5 mg of bosentan (as monohydrate)
  • Each film-coated tablet contains 125 mg of bosentan (as monohydrate)
• The other components are:
  • Tablet core: maize starch, pregelatinized starch, sodium starch glycolate (type A), povidone, glycerol dibehenate and magnesium stearate.
  • Film coating: hypromellose, triacetin, talc, titanium dioxide, yellow iron oxide (E172), red iron oxide (E172) and aqueous dispersion of ethylcellulose (containing ethylcellulose, sodium lauryl sulfate and cetyl alcohol).

Description of the appearance of Bosentan Teva and contents of the pack
(62.5 mg) Bosentan Teva film-coated tablets are pink-orange, round (6 mm diameter), biconvex tablets, with "62.5" engraved on one side.
(125 mg) Bosentan Teva film-coated tablets are pink-orange, oval (dimensions: 11 mm x 5 mm), with "125" engraved on one side.
(62.5 mg) Bosentan Teva is available in packs containing 7, 14, 28, 56, 60 and 112 film-coated tablets in blisters or 7x1, 14x1, 28x1, 56x1, 60x1 and 112x1 film-coated tablets in perforated blister packs for single doses.
(125 mg) Bosentan Teva is available in packs containing 7, 14, 28, 56, 60, 112 and 120 film-coated tablets in blisters or 7x1, 14x1, 28x1, 56x1, 60x1, 112x1 and 120x1 film-coated tablets in perforated blister packs for single doses.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Teva Italia S.r.l. - Piazzale Luigi Cadorna, 4 - 20123 Milano - Italy

Manufacturers responsible for batch release
PLIVA Hrvatska d.o.o. (PLIVA Croatia Ltd.)
Prilaz baruna Filipovica 25, Zagreb
10000 Croatia