long as you are taking Bosentan. We suggest you write the date of your most recent test and also of your next test (ask your doctor for the date) on the Patient Alert Package leaflet: Information for the user Card, to help you remember when your next test is due. Bosentan 62.5 mg film-coated tablets Blood tests for liver function These will be done every month for the duration of Bosentan 125 mg film-coated tablets treatment with Bosentan. After an increase in dose an additional test will be done after 2 weeks. bosentan Blood tests for anaemia Read all of this leaflet carefully before you start These will be done every month for the first 4 months taking this medicine because it contains important of treatment, then every 3 months after that, as patients information for you. taking Bosentan may get anaemia. - Keep this leaflet. You may need to read it again. If these results are abnormal, your doctor may decide - If you have any further questions, ask your doctor to reduce your dose or stop treatment with Bosentan or pharmacist. and to perform further tests to investigate the cause. - This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if Children and adolescents their signs of illness are the same as yours. Bosentan is not recommended in paediatric patients - If you get any side effects, talk to your doctor or with systemic sclerosis and ongoing digital ulcer pharmacist. This includes any possible side effects disease. Please see also section 3. How to take not listed in this leaflet. See section 4. Bosentan. What is in this leaflet Other medicines and Bosentan Tell your doctor or pharmacist if you are taking, have 1. What Bosentan is and what it is used for recently taken or might take any other medicines, 2. What you need to know before you take Bosentan including medicines obtained without a prescription. 3. How to take Bosentan It is especially important to tell your doctor if you are 4. Possible side effects taking: 5. How to store Bosentan • cyclosporine A (a medicine used after transplants 6. Contents of the the pack and other information and to treat psoriasis), which must not be used together with Bosentan 1. What Bosentan is and what it is used for • sirolimus or tacrolimus, which are medicines used Bosentan tablets contain bosentan, which blocks a after transplants, as these are not recommended to naturally occurring hormone called endothelin-1 (ET- be used together with Bosentan 1), which causes blood vessels to narrow. Bosentan • glibenclamide (a diabetes medicine), rifampicin (a therefore causes blood vessels to expand and belongs tuberculosis medicine), fluconazole (a medicine to the class of medicines called “endothelin receptor against fungal infections),ketoconazole (a medicine antagonists”. used to treat Cushing’s syndrome), or nevirapine (an HIV medicine) as these medicines are not Bosentan is used to treat: recommended to be used together with Bosentan. • Pulmonary arterial hypertension (PAH): PAH is • other medicines for the treatment of HIV infection, a disease of severe narrowing of the blood vessels which may require special monitoring if used in the lungs resulting in high blood pressure in the together with Bosentan blood vessels (the pulmonary arteries) that carry • hormonal contraceptives, which are not effective blood from the heart to the lungs. This pressure as the sole method of contraception when you take reduces the amount of oxygen that can get into the Bosentan. Inside your pack of Bosentan tablets blood in the lungs, making physical activity more you will find a Patient Alert Card which you should difficult. Bosentan widens the pulmonary arteries, read carefully. Your doctor and/or gynaecologist will making it easier for the heart to pump blood through establish the contraception which is appropriate for them. This lowers the blood pressure and relieves you. the symptoms. • Other medications for the treatment of pulmonary hypertension: sildenafil and tadalafil; Bosentan is used to treat patients with class III • Warfarine (an anticoagulant agent); pulmonary arterial hypertension (PAH) to improve • Simvastatin (used to treat hypercholesterolemia). exercise capacity (the ability to carry out physical activity) and symptoms. The ‘class’ reflects the Bosentan with food, drink and alcohol seriousness of the disease: ‘class III’ involves marked Bosentan can be taken with or without food. limitation of physical activity. Some improvements have Pregnancy, breast-feeding and fertility also been shown in patients with class II PAH. ‘Class If you are pregnant or breast-feeding, think you may II’ involves slight limitation of physical activity. The PAH be pregnant or are planning to have a baby, ask your for which Bosentan is indicated can be: doctor or pharmacist for advice before taking this • primary (with no identified cause or familial); medicine. • caused by scleroderma (also called systemic Women of child-bearing age sclerosis, a disease where there is abnormal growth Do NOT take Bosentan if you are pregnant or planning of the connective tissue that supports the skin and to become pregnant. other organs); • caused by congenital (inborn) heart defects with Pregnancy tests shunts (abnormal passageways) causing abnormal Bosentan may harm unborn babies conceived before flow of blood through the heart and lungs. starting or during treatment. If you are a woman who • Digital ulcers: (sores on the fingers and toes) in could become pregnant, your doctor will ask you to adult patients with a condition called scleroderma. take a pregnancy test before you start taking Bosentan, Bosentan reduces the number of new finger and and regularly while you are taking Bosentan. toe ulcers that appear. Contraceptives If it is possible that you could become pregnant, use 2. What you need to know before you take a reliable form of birth control (contraception) while Bosentan you are taking Bosentan. Your doctor or gynaecologist Do not take Bosentan: will advise you about reliable contraceptive methods • if you are allergic to bosentan or any of the other while taking Bosentan. Because Bosentan may make ingredients of this medicine (listed in section 6) hormonal contraception (e.g., oral, injection, implant, or • if you have liver problems (ask your doctor) skin patches) ineffective, this method on its own is not • if you are pregnant, or could get pregnant reliable. Therefore, if you use hormonal contraceptives because you are not using reliable contraceptive you must also use a barrier method (e.g., female methods. Please read the information under condom, diaphragm, contraceptive sponge, or your “Contraceptives” and “Other medicines and partner must also use a condom). Inside your pack of Bosentan tablets you will find a Patient Alert Card. You Bosentan” should complete this card and take it to your doctor • (a medicine used if you are taking cyclosporine A at your next visit so that your doctor or gynaecologist after a transplant or to treat psoriasis) can assess whether you need additional or alternative If any of these apply to you, tell your doctor. reliable contraceptive methods. Monthly pregnancy tests are recommended while you are taking Bosentan Warnings and precautions and are of child-bearing age. Talk to your doctor or pharmacist before taking Bosentan. Breast-feeding Tell your doctor immediately if you are breast-feeding. Tests your doctor will do before treatment You are advised to stop breast-feeding if Bosentan is • a blood test to check your liver function prescribed for you, because it is not known whether • a blood test to check for anaemia (low this medicine passes into breast milk. haemoglobin) • a pregnancy test if you are a woman of child- Fertility bearing potential If you are a man taking Bosentan, it is possible that this medicine may lower your sperm count. It cannot Some patients taking Bosentan have been found to be excluded that this may affect your ability to father a have abnormal liver function tests and anaemia (low child. Talk to your doctor if you have any questions or haemoglobin). concerns about this. Tests your doctor will do during treatment Driving and using machines During treatment with Bosentan, your doctor will Bosentan has no or negligible influence on the ability to arrange for regular blood tests to check for changes in drive and use machines. your liver function and haemoglobin level. However, Bosentan can induce hypotension For all these tests please refer also to the Patient (decrease of your blood pressure) which can make Alert Card (inside your pack of Bosentan tablets). It is you feel dizzy, affect your vision and affect your ability important that you have these regular blood tests as to drive and use machines. N11948 Therefore, if you feel dizzy or that your vision is Uncommon (may affect up to one in 100 people): blurred while taking Bosentan, do not drive or • Thrombocytopenia (low number of blood platelets) operate any tools or machines. • Neutropenia/leukopenia (low number of white blood cells) Bosentan contains Sodium: • Elevated liver function tests with hepatitis This medicine contains less than 1 mmol (23 (inflammation of the liver) including possible mg) of sodium per dose, that is to say it is exacerbation of underlying hepatitis and/or jaundice essentially‘sodium-free’. (yellowing of the skin or the whites of the eyes) 3. How to take Bosentan Rare (may affect up to one in 1000 people): • Anaphylaxis (general allergic reaction), angioedema Treatment with Bosentan should only be started and (swelling, most commonly around the eyes, lips, monitored by a doctor who has experience in the tongue or throat) treatment of PAH or systemic sclerosis. Always take • Cirrhosis (scarring) of the liver, liver failure (serious this medicine exactly as your doctor has told you. disturbance of liver function) Check with your doctor or pharmacist if you are not sure.