Endothelin is an important mediator
in pulmonary arterial hypertension

Endothelin (ET-1) levels are elevated in plasma and lung tissues of pulmonary arterial hypertension patients¹

 Elevated levels of ET-1 in plasma and lung tissues suggest a pathogenic role for endothelin in PAH¹

Excess ET-1 has diverse effects^*2-4

Acute Chronic Inflammation Cell proliferation Vascoconstriction Fibrosis   Inflammation   Hypertrophy

Effects of ET-1 are mediated by ET_A and ET_B receptors^*1

ETA activity in PAH ETB activity in PAH Cell proliferation5 Cell proliferation Vascoconstriction4 Vascoconstriction4 Inflammation6 Inflammation6   Fibrosis7   Hypertrophy3

*Statements are based on observations reported from in vitro, animal, and human trials. The clinical significance is unknown.



Tracleer is indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) in patients with WHO Class II-IV symptoms, to improve exercise ability and decrease the rate of clinical worsening. Patients with WHO Class II symptoms showed reduction in the rate of clinical deterioration and a trend for improvement in walk distance. Physicians should consider whether these potential benefits are sufficient to offset liver injury in WHO Class II patients, which may preclude future use as their disease progresses.

Important safety information

Because of the associated risks, Tracleer may be prescribed only through the Tracleer Access Program.

Potential for serious liver injury (including, after prolonged treatment, rare cases of liver failure and unexplained hepatic cirrhosis in a setting of close monitoring)—Liver monitoring of all patients is essential prior to initiation of treatment and monthly thereafter.

High potential for major birth defects—Pregnancy must be excluded and prevented through the use of reliable forms of birth control; monthly pregnancy tests should be obtained.

Contraindicated for use with cyclosporine A and glyburide.

Please see full prescribing information including BOXED WARNING.

Review updated treatment algorithm for PAH

1. Tracleer (bosentan) full prescribing information. Actelion Pharmaceuticals US, Inc. August 2009.
2. Rich S, McLaughlin VV. Pulmonary hypertension. In: Libby P, Bonow RO, Mann DL, Zipes DE, eds. Braunwald's Heart Disease. 2 vols. 8th ed. Philadelphia, PA: Saunders Elsevier; 2008:1883-1914.
3. Giaid A, Yanagisawa M, Langleben D, et al. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med. 1993;328:1732-1739.
4. Miyauchi T, Masaki T. Pathophysiology of endothelin in the cardiovascular system. Annu Rev Physiol. 1999;61:391-415.
5. Davie N, Haleen SJ, Upton PD, et al. ET(A) and ET(B) receptors modulate the proliferation of human pulmonary artery smooth muscle cells. Am J Respir Crit Care Med. 2002;165:398-405.
6. Muller DN, Mervaala EM, Schmidt F, et al. Effect of bosentan on NF-kappaB, inflammation, and tissue factor in angiotensin II-induced end-organ damage. Hypertension. 2000;36:282-290.
7. Katwa LC, Guarda E, Weber KT. Endothelin receptors in cultured adult rat cardiac fibroblasts. Cardiovasc Res. 1993:27:2125-2129.