SPL Set ID: 749e42fb-2fe0-45dd-9268-b43bb3f4081c

TRACLEER ® is the proprietary name for bosentan, an endothelin receptor antagonist that belongs to a class of highly substituted pyrimidine derivatives, with no chiral centers. It is designated chemically as 4-tert-butyl-N-[6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-[2,2´]-bipyrimidin-4-yl]- benzenesulfonamide monohydrate and has the following structural formula: Bosentan has a molecular weight of 569.64 and a molecular formula of C 27 H 29 N 5 O 6 S∙H 2 O. Bosentan is a white to yellowish powder. It is poorly soluble in water (1.0 mg/100 mL) and in aqueous solutions at low pH (0.1 mg/100 mL at pH 1.1 and 4.0; 0.2 mg/100 mL at pH 5.0). Solubility increases at higher pH values (43 mg/100 mL at pH 7.5). In the solid state, bosentan is very stable, is not hygroscopic and is not light sensitive. TRACLEER is available as 62.5 mg and 125 mg film-coated tablets for oral administration, and contains the following excipients: corn starch, ethylcellulose, glyceryl behenate, hydroxypropylmethylcellulose, iron oxide red, iron oxide yellow, magnesium stearate, povidone, pregelatinized starch, sodium starch glycolate, talc, titanium dioxide, and triacetin. Each TRACLEER 62.5 mg tablet contains 64.54 mg of bosentan monohydrate, equivalent to 62.5 mg of anhydrous bosentan. Each TRACLEER 125 mg tablet contains 129.08 mg of bosentan monohydrate, equivalent to 125 mg of anhydrous bosentan. TRACLEER is also available as a 32 mg tablet for oral suspension and contains the following excipients: acesulfame potassium, aspartame (E951), calcium hydrogen phosphate anhydrous, cellulose microcrystalline, croscarmellose sodium, magnesium stearate, silica colloidal anhydrous, tartaric acid, and tutti frutti flavor. Each dispersible tablet contains 1.87 mg of phenylalanine. Each dispersible tablet contains 33.045 mg of bosentan monohydrate, equivalent to 32 mg anhydrous bosentan. Chemical Structure