Bosentan
DefinitionThis section has been translated automatically.
endothelin receptor antagonist, which is approved for the treatment of rare pulmonary hypertension and is the first to offer a targeted intervention with a new mechanism of action.
Spectrum of actionThis section has been translated automatically.
The peptide endothelin mediates a permanent vasoconstriction, which leads to an increase in pressure in the small circulation. Bosentan specifically blocks the endothelin-1-receptors (ETA-receptor and ETB-receptor) on endothelial cells and on smooth muscle cells and thus influences the acute course of the disease, inflammatory processes and the "remodelling" of the endothelial cells (see endotheline below).
IndicationThis section has been translated automatically.
- Approved for the treatment of pulmonary arterial hypertension (PAH), to improve exercise capacity and symptoms in patients with functional class III.
- Efficacy has been shown in primary pulmonary arterial hypertension (PAH) and scleroderma-associated PAH without significant interstitial lung disease. Pulmonary arterial hypertension is a serious concomitant disease for patients with systemic scleroderma. Although there are no figures on life prolongation with bosentan therapy, there is no doubt that the quality of life has improved.
Limited indicationThis section has been translated automatically.
Painful finger ulcerations in progressive systemic scleroderma: Bosentan therapy in clinical studies over 16 weeks resulted in a significant improvement of symptoms. Since endothelin stimulates fibroblasts to produce collagen, it is conceivable that endothelin inhibition by bosentan may have a beneficial effect on the course of PSS.
Pregnancy/nursing periodThis section has been translated automatically.
No sufficient data on use in pregnancy or lactation known. Should not be prescribed during pregnancy or lactation.
Dosage and method of useThis section has been translated automatically.
Initial: 2 times/day 62.5 mg p.o. over 4 weeks. From week 5: 2 times/day 125 mg p.o.
Undesirable effectsThis section has been translated automatically.
Headaches (approx. 20% of patients), nasopharyngitis (10-20% of patients), flushing symptoms (5-10% of patients), liver dysfunction (reversible increase in liver enzymes), leg edema and anemia, hypotension, palpitations, dyspepsia, fatigue and itching, gastroesophageal reflux disease, rectal hemorrhage, facial telangiectasia.
ContraindicationThis section has been translated automatically.
Liver dysfunction with an increase in liver aminotransferases (AST and/or ALT) to more than three times the upper normal value at the start of therapy. Simultaneous application of Ciclosporin.
PreparationsThis section has been translated automatically.
Tracleer film coated tablets
Note(s)This section has been translated automatically.
- Current Clinical Studies:
- In the RAPIDS2 study, 122 patients with PSS-related finger ulcers received either the endothelin antagonist or placebo for 16 weeks. Bosentan significantly reduced the incidence of new digital ulcers while proving safe and well tolerated. Whether bosentan also acts appropriately in PSS-associated pulmonary fibrosis, which is associated with overexpression of ET-1 in the lung, will be shown in the BUILD3 studies by 2005. According to initial results, the antifibrotic and antiproliferative effect of bosentan may have a disease-modifying effect by influencing remodeling and delaying disease progression.
- Diagnostics before use of bosentan:
- Echocardiography as the screening method of choice to assess cardiac function and exclude left ventricular dysfunction or cardiac vitiation.
- ECG: Pathologic in 2/3 of affected individuals.
- X-ray chest: Dilated pulmonary segment and widening of the descending right pulmonary artery demonstrable in > 90%. Peripheral vessels are often rarefied.
- Doppler echocardiography: Confirmation and quantification of the diagnosis of pulmonary hypertension.
- Angiography and cardiac catheterization should be reserved for specialized centers for the purpose of planning optimal therapy.
LiteratureThis section has been translated automatically.
- Channick RN et al (2001) Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet 358: 1119-1123
- Dietrich CG et al (2002) Bosentan for pulmonary hypertension. N Engl J Med 347: 292-294
- Kenyon KW et al (2003) Bosentan for the treatment of pulmonary arterial hypertension. Ann Pharmacother 37: 1055-1062
- Pereira BN et al (2002) Bosentan for pulmonary hypertension. N Engl J Med 347: 292-294
- Rubin LJ et al (2002) Bosentan therapy for pulmonary arterial hypertension. N Engl J Med 346: 896-903
- Sitbon O et al (2003) Effects of the dual endothelin receptor antagonist bosentan in patients with pulmonary arterial hypertension: a 1-year follow-up study. Chest 124: 247-254