Description

Hypersensitivity to the active substance or to any of the excipients Moderate to severe hepatic impairment, i.e., Child-Pugh class B or C. Baseline values of liver aminotransferases, i.e., aspartate aminotransferases (AST) and/or alanine aminotransferases (ALT), greater than 3 times the upper limit of normal Concomitant use of cyclosporine A. Pregnancy Special warnings and precautions for use Liver aminotransferase levels must be measured prior to initiation of treatment and subsequently at monthly intervals for the duration of treatment with Bosentan. ln addition, liver aminotransferase levels must be measured 2 weeks after any dose increase.

Treatment with bosentan has been associated with dose dependent elevations in liver aminotransferases and decreases in haemoglobin concentration. Other side effects include Anaemia, haemoglobin decrease, Thrombocytopenia, Neutropenia, leucopenia, Hypersensitivity reactions, Headache, Syncope, Palpitations, Flushing, Hypotension, Gastroesophageal reflux disease, Aminotransferase elevations associated with hepatitis and/or jaundice, Liver cirrhosis, liver failure (rarely), Erythema, Diarrhoea, Oedema, fluid retention.

Bosentan is contraindicated in pregnancy. lt is not known whether bosentan is excreted into human breast milk. Breast-feeding is not recommended during treatment with Bosentan.

Consider discontinuation of therapy if pulmonary oedema occurs. Avoid abrupt withdrawal and consider dose reduction (e.g. half the dose for 3-7 days) to minimise risk of clinical deterioration. Lactation. Bosentan may cause dizziness, which could affect the ability to drive or use machines.

Dosage in hepatic impairment: No dose adjustment is needed in patients with mild hepatic impairment. Bosentan is contraindicated in patients with moderate to severe liver dysfunction. Dosage in renal impairment: No dose adjustment is required in patients with renal impairment. No dose adjustment is required in patients undergoing dialysis. Dosage in elderly patients: No dose adjustment is required in patients over the age of 65 years. Hepatic impairment: ln patients with mildly impaired liver function (Child-Pugh class A) no relevant changes in the pharmacokinetics have been observed. The pharmacokinetics of Bosentan have not been studied in patients with Child-Pugh class B or C hepatic impairment and Pulmoten is contra-indicated in this patient population. Renal impairment: No dose adjustment is required in patients with renal impairment. There is no specific clinical experience in patients undergoing dialysis. Based on physicochemical properties and the high degree of protein binding, bosentan is not expected to be removed from the circulation by dialysis to any significant extent.

Anti-hypertensive, Endothelin receptor antagonist