Treatment of pulmonary arterial hypertension (PAH) to improve exercise capacity and symptoms in patients with WHO functional class Ill. Efficacy has been shown in: Some improvements have also been shown in patients with PAH WHO functional class ll.
Bosentan is a dual endothelin receptor antagonist (ERA) with affinity for both endothelin A and B (ETA and ETB) receptors. Bosentan decreases both pulmonary and systemic vascular resistance resulting in increased cardiac output without increasing heart rate. The neurohormone endothelin-1 (ET-1) is one of the most potent vasoconstrictors known and can also promote fibrosis, cell proliferation, cardiac hypertrophy and remodelling, and is pro-inflammatory. These effects are mediated by endothelin binding to ETA and ETB receptors located in the endothelium and vascular smooth muscle cells. ET-1 concentrations in tissues and plasma are increased in several cardiovascular disorders and connective tissue diseases, including pulmonary arterial hypertension, scleroderma, acute and chronic heart failure, myocardial ischaemia, systemic hypertension and atherosclerosis, suggesting a pathogenic role of ET-1 in these diseases. In pulmonary arterial hypertension and heart failure, in the absence of endothelin receptor antagonism, elevated ET-1 concentrations are strongly correlated with the severity and prognosis of these diseases. Absorption : In healthy subjects, the absolute bioavailability of bosentan is approximately 50% and is not affected by food. The maximum plasma concentrations are attained within 3-5 hours. Distribution : Bosentan is highly bound (>98%) to plasma proteins, mainly albumin. Elimination : Bosentan is eliminated by biliary excretion following metabolism in the liver by the cytochrome P450 isoenzymes, CYP2C9 and CYP3A4. Less than 3% of an administered oral dose is recovered in urine.
Always consult a registered doctor before taking any medicine. This information is for general knowledge only.
Tablets are to be taken orally morning and evening, with or without food. Pulmonary arterial hypertension : ln adult patients, Bosentan treatment should be initiated at a dose of 62.5 mg twice daily for 4 weeks and then increased to the maintenance dose of 125 mg twice daily. For paediatric patients aged 2 years or older, the optimal maintenance dose has not been defined in well-controlled studies. However, paediatric pharmacokinetic data have shown that Bosentan plasma concentrations in children were on average lower than in adult patients and were not increased by increasing the dose of Bosentan above 2 mg/kg body weight twice daily. Discontinuation of treatment : lf the decision to withdraw Bosentan is taken, it should be done gradually while an alternative therapy is introduced.
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.
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.
Increased bosentan levels with CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, diltiazem), CYP2C9 inhibitors (e.g. amiodarone, fluconazole), tacrolimus. Rifampicin initially increases but subsequently decreases bosentan concentration. May decrease plasma levels of warfarin, statins (e.g. simvastatin, lovastatin), hormonal contraceptives, sildenafil, tadalafil.
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. Pulmoten may cause dizziness, which could affect the ability to drive or use machines.