Excess ET has diverse effects*1-3

Produced primarily by vascular endothelial cells4
ET-mediated cardiopulmonary vascular and structural changes accompany disease progression in PAH*
*Statements are based on observations reported from in vitro or animal trials. The clinical significance in humans is unknown.

PAH is associated with increased plasma levels of ET in the pulmonary vasculature5

ET concentrations are elevated in plasma and lung tissues in PAH patients, suggesting a pathogenic role for ET in PAH6

Dual endothelin receptor antagonism of both the ETA and ETB receptors modulates the effects of excess ET*

*Statements are based on observations reported from in vitro or animal trials. The clinical significance in humans is unknown.

Dual ERA competitively binding to ETA and ETB in pathologic conditions.

Tracleer is indicated for the treatment of pulmonary arterial hypertension (PAH) 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 the risk of 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.

REFERENCES

1. Braunwald E, Zipes DP, Libby P, eds. Heart Disease. 2 vols. 6th ed. Philadelphia, PA: WB Saunders Co; 2001:1912.

2. Sirois MG, Filep JG, Rousseau A, et al. Endothelin-1 enhances vascular permeability in conscious rats: role of thromboxane A2. Eur J Pharmacol. 1992;214:119–125.

3. 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.

4. Miyauchi T, Masaki T. Pathophysiology of endothelin in the cardiovascular system. Annu Rev Physiol. 1999;61:391–415.

5. 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.

6. Yoshibayashi M, Nishioka K, Nakao K, et al. Plasma endothelin concentrations in patients with pulmonary hypertension associated with congenital heart defects. Evidence for increased production of endothelin in pulmonary circulation. Circulation. 1991;84:2280–2285.