Bosentan

• While taking bosentan you should see your treating specialist regularly to make sure the treatment is working and to minimise any possible side effects.
• Bosentan should be taken at the same time each day.
• You should not stop your treatment unless your doctor tells you to.
• You should not increase or reduce the dose of bosentan unless your doctor tells you to.
• Contact your doctor at once if you experience symptoms such as nausea, stomach pain, fever, loss of appetite, dark urine, clay-coloured stools or jaundice (yellowing of the skin and/or eyes).
• Bosentan interacts with many other drugs. Discuss with your doctor whether you need to change the doses of these drugs or avoid using them together with bosentan (such as cyclosporin and the diabetes medication glibenclamide).

Bosentan helps lower blood pressure in the lungs by opening up the lung blood vessels. This helps your heart pump blood more efficiently through the blood vessels in the lungs.

Bosentan can reduce the symptoms of PAH and in some cases prolong life expectancy. It may take 2 months or more before your symptoms start to improve.

Before bosentan can be prescribed, a specialist will assess you. This may be a rheumatologist, immunologist, cardiologist (heart) or a respiratory (lung) physician who has experience in managing PAH.

You will be asked to have the following tests:

• an ultrasound scan of your heart (echocardiogram)
• a right heart catheter – this is a test to measure the blood pressure in your heart and lungs. It involves inserting a tube into your heart from an artery in your neck, arn or groin.
• a six minute walk test (6MWT) to measure how far you can walk in six minutes.

Every six months you will be asked to have the echocardiogram and the 6MWT to check that bosentan is still helping your condition.

Bosentan is a tablet. It comes in two strengths (62.5 mg and 125mg).

What is the dosage and when should it be taken?

For the first month, the dose is one 62.5 mg tablet twice a day. If tests to check blood counts and liver function are satisfactory, the dose is then increased to one 125mg tablet twice a day. Adults who weigh < 40kg may remain on a lower dose.

Bosentan should be taken at the same time each day. It is usually taken in the morning and at night. If you forget to take a dose you can take it later in the day. If it is the next day, take the normal dose (do not take a double dose). Bosentan does not have to be taken with food.

Can other medicines be taken with bosentan?

Bosentan may be taken in combination with other medicines including:

• steroid medicines such as prednisolone
• anti-inflammatory medicines (NSAIDs) such as naproxen (Naprosyn) or ibuprofen (Brufen/Nurofen) provided your kidney and heart function is normal
• pain-relieving medicines such as paracetamol.
• calcium channel blockers (for Raynaud’s disease)
• diuretics (fluid tablets)
• warfarin (blood-thinning medicine)
• other treatments for PAH.

There are a number of medicines that should not be taken when you are taking bosentan (see Precautions).

How long is the treatment continued?

Bosentan may be given on a long term basis provided it does not cause problems and continues to help your condition. It is usually given for as long as the 6-monthly tests (echocardiogram and the 6MWT) show that it is of benefit.

Do not stop taking bosentan without first talking to your doctor. If your doctor decides to stop the treatment, you may need to reduce the dose gradually before you stop the medicine completely.

Most people who take bosentan do not experience side effects. Tell your doctor if you are worried about possible side effects. Having a lower dose may reduce side effects so that you can continue taking bosentan.

Most common possible side effects

• The most common side effects include stomach upset, nausea, diarrhea and headache.
• Other side effects include inflamed throat, irritated nose passages or skin rash.
• Dizziness due to low blood pressure, flushing, ankle and/or leg swelling can occur.
• Irregular heart beats or tiredness have been reported.

Less common or rare possible side effects

• Bosentan can cause severe liver problems. Symptoms include nausea, stomach pain, low-grade fever, loss of appetite, dark urine, clay-coloured stools and jaundice (yellowing of the skin and/or eyes). Call your doctor at once if you have any of these symptoms.
• Low haemoglobin (anaemia) can be detected on blood tests but rarely causes symptoms.
• There are also a number of other rare side effects.

Blood tests

• Your liver function and blood counts for haemoglobin will need to be tested before you start taking bosentan, and again each month during your treatment.

Use with other medicines

• Bosentan can interact with other medicines. You should tell your doctor (including your GP, rheumatologist and other health professionals) about all medicines you are taking or plan to take. This includes over-the-counter or herbal/naturopathic medicines.
• The following medicines should NOT be taken with bosentan.
  • Ciclosporin (Cicloral, Neoral, Sandimmune)
  • Glibenclamide (a medication used to treat diabetes).
• The following are some of the medicines that may interfere with bosentan. Some should not be taken with bosentan. For others, the dose may need to be adjusted:
  • warfarin (a blood thinning medicine) – close monitoring is required if you start bosentan while taking warfarin as the warfarin dose may need to be adjusted;
  • hormone-based birth control, such as contraceptive pills, shots, patches and implants (see under ‘pregnancy and breastfeeding’);
  • imatinib (a cancer treatment)
  • some cholesterol lowering medicines;
  • anti-fungal medicines;
  • HIV/AIDS medicines such as lopinavir or ritonavir (Kaletra, Norvir);
  • tacrolimus (used to prevent rejection of liver or kidney transplants);
  • rifampicin (used for tuberculosis).

Fertility

• Most vaccines can be given safely with bosentan. Pnewmovax and yearly flu vaccinations are safe and recommended to reduce your risk of those infections. Talk with your rheumatologist before receiving any vaccines.

Fertility

• Bosentan may lower sperm counts in some men. This may affect your ability to father children.

Use during pregnancy and breastfeeding

• Bosentan should not be taken if you are planning pregnancy, during pregnancy or when breastfeeding.
• If you are a woman of childbearing age, you should use effective contraception while taking bosentan. Bosentan may make the contraceptive pill unreliable, therefore you should use barrier methods of contraception. It is important to discuss this with your doctor before you start bosentan.
• If you are planning a family or become pregnant during your treatment, you should discuss this with your doctor as soon as possible.

• Store bosentan at room temperature, away from heat, moisture and light (e.g. not in the bathroom).
• Keep all medicines out of reach of children.