Bosentan therapy for pulmonary arterial hypertension - Toxicity Limits

Bosentan therapy for pulmonary arterial hypertension
Jun 2004
H Cohen, C Chahine, A Hui, and R Mukherji
American Journal of Health-System Pharmacy
PURPOSE: The etiology, epidemiology, pathophysiology, diagnosis, and manifestations of pulmonary arterial hypertension (PAH) are described, and the role of bosentan in the management of PAH is reviewed.
SUMMARY: The incidence of primary pulmonary hypertension, a subcategory of PAH, is estimated to be one to two new cases per million people annually in the general population. PAH has definitively been linked with several appetite suppressants. Disease-induced causes of PAH include connective tissue diseases, portal hypertension or liver disease, and human immunodeficiency virus infection. The clinical diagnosis of early PAH is difficult because its symptoms are nonspecific. Exertional dyspnea, the most common symptom of PAH, occurs in 60% of patients and indicates a severely compromised cardiac output. Three dependent elements are integral to the development of elevated mean pulmonary arterial pressure and PAH: vascular wall remodeling, thrombosis in situ, and vasoconstriction. Bosentan undergoes extensive hepatic metabolism. Bosentan-induced hepatotoxicity is common and must be monitored carefully throughout therapy. Since PAH is common in women of childbearing age, the use of bosentan in these patients requires careful review. Limited data exist on the use of bosentan in children, but one small study found that treatment with the drug resulted in hemodynamic improvement for pediatric patients with PAH.
CONCLUSION: Prostacyclin analogues are the most effective agents for managing PAH, but their use is hampered by the need for parenteral therapy. Oral bosentan is a novel treatment alternative for patients with PAH. Further trials are necessary to determine bosentan's onset of action, consistency, durability, and magnitude of effect in different populations with PAH and its impact on survival.
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