Start Tracleer first Tracleer consistently improved outcomes as first-line therapy   Improved and maintained exercise capacity (FC III, IV)*1,2   Improved hemodynamics in mild to severe patients (FC II, III)*2-4   Maintained or improved functional class status (FC II, III, IV)1-3   Reduced rate of clinical worsening (FC II, III, IV)1-3 *The relationship between hemodynamic effects and 6-minute walk distance is unknown.

FC functional class.

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 Tracleer and exercise capacity

BREATHE-1 Multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of Tracleer (125 mg BID, 250 mg BID) in patients with WHO functional class III or IV pulmonary arterial hypertension (N=213). All patients (n=144 in the Tracleer group and n=69 in the control group) participated in the first 16 weeks. A subset of this population (n=35 in the Tracleer group and n=13 in the control group) continued for up to 28 weeks. Clinical worsening was defined as the combined endpoint of death, hospitalization for treatment related to PAH, discontinuation of therapy due to worsening PAH, or initiation of epoprostenol therapy.^1,5

Study 351 Randomized, double-blind, placebo-controlled study of Tracleer 125 mg BID vs placebo in patients with WHO functional class III or IV pulmonary arterial hypertension (N=32). Clinical worsening defined as right ventricular heart failure or aggravated pulmonary hypertension.²

EARLY Endothelin Antagonist tRial in miLdlY symptomatic PAH patients. The first and only randomized, double-blind, placebo-controlled trial conducted solely in mildly symptomatic (functional class II) patients with PAH (N=185). Patients were randomized to Tracleer (62.5 mg BID, 125 mg BID) or placebo. Trial duration was 6 months. Concomitant use of anticoagulants and calcium channel blockers was allowed. Both the Tracleer group and the placebo group included some patients on sildenafil at baseline (Tracleer, n=14; placebo, n=15). Clinical worsening defined as death, hospitalization due to PAH, or symptomatic progression of PAH.³

BREATHE-5 Randomized, double-blind, placebo-controlled trial in adults with PAH associated with Eisenmenger syndrome (N=54). Patients were randomized to Tracleer (62.5 mg BID, 125 mg BID) or placebo. Background therapies included anticoagulants, vasodilators, diuretics, and supplemental oxygen.⁴

1. Rubin LJ, Badesch DB, Barst RJ, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med. 2002;346:896-903.
2. Channick RN, Simonneau G, Sitbon O, et al. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet. 2001;358:1119-1123.
3. Galiè N, Rubin LJ, Hoeper MM, et al. Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomised controlled trial. Lancet. 2008;371:2093-2100.
4. Galiè N, Beghetti M, Gatzoulis MA, et al. Bosentan therapy in patients with Eisenmenger syndrome: a multicenter, double-blind, randomized, placebo-controlled study. Circulation. 2006;114:48-54.
5. Tracleer (bosentan) full prescribing information. Actelion Pharmaceuticals US, Inc. August 2009.