Pulmoten

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

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.

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.

Pregnancy: Bosentan is contraindicated in pregnancy.

Use during lactation: lt is not known whether bosentan is excreted into human breast milk. Breast-feeding is not recommended during treatment with Bosentan.

Effects on ability to drive and use machines: Bosentan may cause dizziness, which could affect the ability to drive or use machines.

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.

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.

Anti-hypertensive, Endothelin receptor antagonist

Symptoms: Nausea, vomiting, hypotension, dizziness, sweating and blurred vision.

Management: Symptomatic and supportive treatment.

Store below 30°C. Store in a cool and dry place, protected from light. Keep out of children’s reach.