Apo-Bosentan: Uses, Side Effects and Dosage

ABOUT THIS MEDICATION

What the medication is used for:

APO-BOSENTAN (bosentan) tablets are prescribed for the treatment of pulmonary arterial hypertension (high blood pressure in the blood vessels between the heart and the lungs).

What it does:

APO-BOSENTAN reduces abnormally high blood pressure by relaxing these blood vessels. APO-BOSENTAN tablets belong to the class of medicines known as endothelin receptor antagonists.

Before you take APO-BOSENTAN:

Tests your doctor will do before treatment:

• a blood test for liver function;

• a blood test for anemia (reduction in red blood

  cells);

• a pregnancy test.

When it should not be used:

Do not use APO-BOSENTAN if you:

• are hypersensitive (allergic) to bosentan or any

  other ingredients in the tablet (See What the important nonmedicinal ingredients are);

• have liver problems;

• are pregnant or planning to become pregnant

  (hormonal contraceptives alone are not effective when you take APO-BOSENTAN);

• are a woman of childbearing age and not using

  adequate contraceptive methods;

• are being treated with cyclosporine A, or

  glyburide.

Tell your doctor immediately if you are pregnant or plan to become pregnant in the near future. This is

because APO-BOSENTAN may harm your unborn baby and you must not take APO-BOSENTAN if you are pregnant. You must also not become pregnant while taking APO-BOSENTAN. If you are a woman of childbearing age, your doctor or gynecologist will advise you about adequate contraceptive methods while taking APO-BOSENTAN. Because APO-BOSENTAN may make hormonal contraception (e.g., oral, injection, implant or skin patches) ineffective, this method on its own 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). Monthly pregnancy tests are recommended while you are taking APO-BOSENTAN and you are of childbearing age.

Tell your doctor immediately if you are breastfeeding. You are advised to stop breastfeeding if APO-BOSENTAN is prescribed for you because it is not known if this drug passes into the milk in women who are taking APO-BOSENTAN.

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

If you feel dizzy while taking APO-BOSENTAN, do not drive or operate any tools or machines.

APO-BOSENTAN is not recommended for children.

What the medicinal ingredient is:

Bosentan monohydrate.

What the important nonmedicinal ingredients are:

Colloidal silicon dioxide, crospovidone, magnesium stearate, methyl cellulose and poloxamer. The film-coating is composed of hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyethylene glycol, titanium Dioxide, euroxide red iron oxide and yellow iron oxide.

What dosage forms it comes in:

APO-BOSENTAN 62.5 mg is available as orange-white coloured, round-shaped biconvex film-coated tablets engraved "APO" on one side and "62.5" on the other side.

APO-BOSENTAN 125 mg is also available as orange-white coloured, oval-shaped biconvex film-coated tablets engraved "APO" on one side and "125" on the other side.

WARNINGS AND PRECAUTIONS

Warnings and Precautions

Before you use APO-BOSENTAN 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;
• breastfeeding;
• hypersensitive (allergic) to bosentan or any other ingredients of APO-BOSENTAN.

Before starting APO-BOSENTAN 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 APO-BOSENTAN);

• 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 bosentan 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 APO-BOSENTAN. When your blood test results for liver function return to normal, your doctor may decide to restart treatment with APO-BOSENTAN.

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 APO-BOSENTAN 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 APO-BOSENTAN.

INTERACTIONS WITH THIS MEDICATION

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

PROPER USE OF THIS MEDICATION

Always take APO-BOSENTAN 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 APO-BOSENTAN.

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 APO-BOSENTAN, 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 APO-BOSENTAN may lead to a worsening of your symptoms. Do not stop taking APO-BOSENTAN unless your doctor tells you to. Your doctor may tell

you to reduce the dose over a few days before stopping completely.

SIDE EFFECTS AND WHAT TO DO ABOUT THEM

Like all medicines, APO-BOSENTAN 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 APO-BOSENTAN or if any of the side effects mentioned above worries you, please inform your doctor or pharmacist.

This is not a complete list of side effects. For any unexpected effects while taking APO-BOSENTAN, contact your doctor or pharmacist.

HOW TO STORE IT

Keep out of reach and sight of children. Store at room temperature 15 °C to 30 ºC. Do not use after the expiry date stated on the blister or bottles.

Reporting Side Effects

You can report any suspected side effects associated with the use of health products to Health Canada by:

• Visiting the Web page on Adverse Reaction

  Reporting (https://www.canada.ca/en/health-canada/services/drugs-health-products/medeffect-canada/adverse-reaction-reporting.html) for information on how to report online, by mail or by fax; or

• Calling toll-free at 1-866-234-2345.

NOTE: Contact your health professional if you need information about how to manage your side effects.

The Canada Vigilance Program does not provide medical advice.

MORE INFORMATION

If you want more information about APO-BOSENTAN:

• Talk to your healthcare professional

• Find the full product monograph that is prepared for healthcare professionals and includes this patient medication information by visiting the Health Canada website (https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-database.html); the manufacturer’s website

  http://www.apotex.ca/products, or by calling 1-800-667-4708.

Date of revision: October 23, 2018