Tracleer (Bosentan)

Serious Warnings and Precautions

Before you use TRACLEER talk to your doctor or pharmacist if you are:

• known to have liver problems;
• pregnant or thinking of becoming pregnant;
• a woman of childbearing age and not using adequate contraceptive methods;
• breast-feeding;
• hypersensitive (allergic) to bosentan or any other ingredients of TRACLEER.

Before starting TRACLEER treatment, tell your doctor and your pharmacist if you are taking or have recently taken any other medicines, even those you have bought yourself. It is especially important to tell your doctor if you are taking:

• hormonal contraceptives (as these may not be effective as the sole method of contraception when you take TRACLEER);
• glyburide (for diabetes);
• cyclosporine A (a medicine used after transplants and to treat psoriasis), or any other drugs used to prevent rejection of transplanted organs;
• fluconazole (to treat fungal infections);
• rifampicin (to treat tuberculosis);
• vasodilators (drugs used to treat high blood pressure).

Tests during treatment:

Some patients taking TRACLEER were found to have abnormal liver function values (increase in liver enzymes) and some patients developed anemia (reduction in red blood cells). Because these findings may not cause symptoms you can feel or observe yourself, your doctor will do regular blood tests to assess any changes in your liver function and hemoglobin level.

Liver function:

This blood test will be done:

• every month or more frequently, if needed.

If you develop abnormal liver function, your doctor may decide to reduce your dose or stop treatment with TRACLEER. When your blood test results for liver function return to normal, your doctor may decide to restart treatment with TRACLEER.

Anemia:

This blood test will be done:

• after 1 month and after 3 months of treatment;
• every 3 months during treatment thereafter.

If you develop anemia, your doctor may decide to perform further tests to investigate the cause.

Your regular blood tests, both for liver function and anemia, are an important part of your treatment. We suggest you write in a diary the date of your most recent test and also that of your next test (ask your doctor for the date) to help you remember when your next test is due.

Pregnancy tests for women of childbearing age:

Due to the risk of failure of hormonal contraception when taking TRACLEER and the risk in patients with pulmonary hypertension of rapid and severe deterioration of the disease, monthly pregnancy tests are recommended before and during treatment with TRACLEER.

Like all medicines, TRACLEER can have side effects even when used as directed.

If you notice yellowing of the skin or eyes (jaundice) or other symptoms such as nausea, vomiting, fever, abdominal pain or unusual tiredness, see your doctor immediately because this may be related to abnormal liver function.

Headaches were the most common side effect in clinical studies.

You may also notice one or more of the following side effects:

• flushed appearance, inflammation of the throat and nasal passages, swelling of the legs and ankles, or other signs of fluid retention, low blood pressure, irregular heartbeat, heartburn, tiredness, itching, nasal congestion, nausea. If these side effects become bothersome, contact your doctor.

Other less common side effects that you might notice:

• vomiting, abdominal pain, diarrhea, skin rash.

If you notice any other side effects or signs of allergic reaction (e.g. swelling of the face or tongue, rash, pruritus) while you are taking TRACLEER or if any of the side effects mentioned above worries you, please inform your doctor or pharmacist.

Drugs that may interact with TRACLEER include: warfarin, simvastatin and other statins, glyburide, ketoconazole, cyclosporine A, tacrolimus, sirolimus and hormonal contraceptives.

Always take TRACLEER exactly as your doctor has instructed you. You should check with your doctor or pharmacist if you are unsure.

Usual dose:

The usual dose is one tablet, swallowed twice daily (morning and evening), consistently with or without food. Swallow the tablet with water. For the first 4 weeks, you will take a 62.5 mg tablet twice daily, from then on, your doctor will advise you to take a 125 mg tablet twice daily, depending on how you react to TRACLEER.

Overdose:

If you take more tablets than you have been told to take, see a doctor or go to a hospital immediately.

Missed dose:

If you forget to take TRACLEER, take a dose as soon as you remember, then continue to take your tablets at the usual time. Do not take a double dose to make up for forgotten tablets.

Stopping treatment:

Suddenly stopping your treatment with TRACLEER may lead to a worsening of your symptoms. Do not stop taking TRACLEER unless your doctor tells you to. Your doctor may tell you to reduce the dose over a few days before stopping completely.