TRACLEER 62.5 mg FILM-COATED TABLETS

2. What you need to know before you take Tracleer

Do not take Tracleer

• to bosentanor any of the other ingredients of this medicine (listed in section 6)
• (ask your doctor)
• because you are not using reliable contraceptive methods. Please read the information in the sections “Contraceptives” and “Other medicines and Tracleer”
• (a medicine used after transplants or to treat psoriasis)

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

Warnings and precautions

Tests that your doctor will perform before prescribing the treatment

• a blood test to assess liver function
• a blood test to detect if you have anemia (low hemoglobin)
• a pregnancy test if you are a woman of childbearing age

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

Blood tests that your doctor will perform during treatment

During treatment with Tracleer, your doctor will schedule regular blood tests to

monitor changes in your liver function and hemoglobin levels.

For all these tests, please refer to the Patient Alert Card (inside the box of Tracleer tablets). It is essential that you have regular blood tests while taking Tracleer. We suggest that you write the date of the most recent test and also your next test (ask your doctor for the date) on the Patient Alert Card to help you remember when you have your next visit.

Liver function blood tests

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

Anemia blood tests

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

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

Children and adolescents

Tracleer is not recommended in pediatric patients with systemic sclerosis with active digital ulcers. See also section 3. How to take Tracleer.

Other medicines and Tracleer

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines, including those obtained without a prescription. It is especially important that you inform your doctor if you are taking:

• ciclosporin A (a medicine used after transplants or to treat psoriasis) that must not be taken with Tracleer.
• sirolimus or tacrolimus, which are medicines used after transplants, and are not recommended to be taken with Tracleer.
• glibenclamide (a medicine for diabetes), rifampicin (a medicine for tuberculosis), fluconazole (an antifungal medicine), ketoconazole (a medicine used to treat Cushing's syndrome), or nevirapine (a medicine for HIV) as these medicines are not recommended to be taken with Tracleer.

• other medicines for the treatment of HIV infection, which when taken with Tracleer may require special monitoring.
• oral contraceptives, which are not effective as the only contraceptive method when taking Tracleer. Inside the box of Tracleer tablets, you will find a Patient Alert Card that you must read carefully. Your doctor and/or gynecologist will determine the appropriate contraceptive method for you.
• other medicines for the treatment of pulmonary hypertension: sildenafil and tadalafil;
• warfarin (an anticoagulant);
• simvastatin (used to treat high cholesterol).

Driving and using machines

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

Women of childbearing age

Do not take Tracleer if you are pregnant or planning to become pregnant.

Pregnancy tests

Tracleer may affect unborn children conceived before or during treatment. If you are a woman of childbearing age, your doctor will ask you to have a pregnancy test before starting treatment with Tracleer and regularly while taking Tracleer.

Contraceptives

If you may become pregnant, use a reliable contraceptive method (contraception) while taking Tracleer. Your doctor or gynecologist will advise you on reliable contraceptive methods while taking Tracleer. Since Tracleer may make hormonal contraception ineffective (e.g., oral, injection, implant, or transdermal 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 also use a condom). Inside the box of Tracleer tablets, you will find a Patient Alert Card. You must complete this card and bring it to your doctor at your next visit so that your doctor or gynecologist can determine if you need an alternative or additional reliable contraceptive method. It is recommended to have a monthly pregnancy test while taking Tracleer and being of childbearing age.

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

Breast-feeding

Tell your doctorimmediately if you are breast-feeding. You are advised to stop breast-feeding if you are prescribed Tracleer, as it is not known whether this medicine passes into breast milk.

Fertility

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

Tracleer contains sodium

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

3. How to take Tracleer

Treatment with Tracleer should only be started and controlled by a doctor who has experience in the treatment of PAH or systemic sclerosis. Follow exactly the administration instructions of this medicine as indicated by your doctor. If you are in doubt, consult your doctor or pharmacist again.

Use of Tracleer with food and drinks

Tracleer can be taken with or without food.

The recommended dose is

Adult

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

Children and adolescents

The recommended dose in children is only for PAH. For children from 1 year of age, treatment with Tracleer usually starts with 2 mg per kg of body weight twice a day (morning and evening). Your doctor will advise you on the dose.

Please note that Tracleer is also available in 32 mg dispersible tablets, which may facilitate dosing in children and patients with low weight or difficulty swallowing film-coated tablets.

If you feel that the effect of Tracleer is too strong or too weak, talk to your doctor to check if you need a dose adjustment.

How to take Tracleer

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

If you take more Tracleerthan you should

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

If you forget to take Tracleer

If you forget to take Tracleer, take the dose as soon as you remember and then continue taking it at your usual schedule. Do not take a double dose to make up for forgotten doses.

If you stop taking Tracleer

If you suddenly stop taking Tracleer, your symptoms may worsen. Do not stop taking Tracleer unless your doctor tells you to. Your doctor may advise you to reduce the dose for a few days before stopping it completely.

If you have any further questions on the use of this medicine, ask 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 with Tracleer are:

• Abnormal liver function that may affect more than 1 in 10 people
• Anemia (low blood value) that may affect more than 1 in 10 people. Anemia may occasionally require blood transfusion.

Your liver and blood values will be tested during treatment with Tracleer (see section 2). It is essential that you have these tests as your doctor has prescribed.

Signs that your liver may not be working properly include:

• nausea (feeling sick)
• vomiting
• fever (high temperature)
• stomach pain (abdomen)
• jaundice (yellowing of the skin or the whites of the eyes)
• dark-colored urine
• itching of the skin
• lethargy or fatigue (unusual tiredness or exhaustion)
• Pseudoflu syndrome (joint and muscle pain with fever)

If you have any of these symptoms, consult your doctor immediately

Other side effects

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

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

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

• flushing (redness of the skin)

• hypersensitivity reactions (including skin inflammation, itching, and skin rash)
• gastroesophageal reflux (acid reflux)
• diarrhea

• fainting (fainting)
• palpitations (rapid or irregular heartbeats)
• low blood pressure

• nasal congestion

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

• thrombocytopenia (decrease in platelet count)
• neutropenia/leukopenia (decrease in white blood cell count)
• elevated liver function tests with hepatitis (inflammation of the liver) including possible exacerbation of hepatitis and/or jaundice (yellowing of the skin or the whites of the eyes)

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

• anaphylaxis (generalized allergic reaction), angioedema (swelling, most frequently around the eyes, lips, tongue, or throat)
• liver cirrhosis (fibrosis), liver failure (severe impairment of liver function)

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

Side effects in children and adolescents

The side effects that have been observed in children treated with Tracleer are the same as in adults.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible that they are not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Tracleer

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 on the blister after “EXP”.

For high-density polyethylene white bottles, use within 30 days of first opening.

For PVC/PE/PVDC/aluminum blisters:

Do not store above 30 °C.

For high-density polyethylene white bottles:

No special storage conditions are required.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Tracleer

• Tracleer 62.5mg film-coated tablets:The active substance is bosentan monohydrate. Each tablet contains 62.5 mg of bosentan (as monohydrate).

• The other componentsof the tablet core are cornstarch, pregelatinized starch, sodium carboxymethyl starch (Type A), povidone, glycerol dibehenate, and magnesium stearate. The film coatingcontains hypromellose, glycerol triacetate, talc, titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172), and ethylcellulose.

Appearance and Package Contents

Tracleer 62.5 mg are round, orange-white, film-coated tablets engraved with «62.5» on one side.

PVC/PE/PVDC/aluminum blisterscontaining 14 film-coated tablets. The packs contain 14, 56, or 112 film-coated tablets (Tracleer 62.5 mg film-coated tablets).

High-density polyethylene (HDPE) white bottles with a silica gel desiccantcontaining 56 film-coated tablets. Cardboard box containing 56 film-coated tablets (Tracleer 62.5 mg film-coated tablets).

Do not swallow the desiccant.

Only some pack sizes may be marketed.

Marketing Authorization Holder:

Janssen-Cilag International NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

Manufacturer:

Actelion Manufacturing GmbH

Emil-Barell-Strasse 7

79639 Grenzach-Wyhlen

Germany

Janssen Pharmaceutica NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

You can request more information about this medicinal product by contacting the local representative of the Marketing Authorization Holder.

Date of the Last Revision of this Leaflet:

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu/.