FDA approved Tracleer (bosentan) for Pulmonary Arterial HypertensionFDA approved New Oral Drug Tracleer for a Rare Type of High Blood Pressure in the Lungs

Bosentan is an endothelin receptor antagonist. The label does not provide further mechanistic details.

Tracleer is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1): - In adults to improve exercise ability and to decrease clinical worsening. Studies establishing effectiveness included predominantly patients with WHO Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (60%), PAH associated with connective tissue diseases (21%), and PAH associated with congenital heart disease with left-to-right shunts (18%). - In pediatric patients aged 3 years and older with idiopathic or congenital PAH to improve pulmonary vascular resistance (PVR), which is expected to result in an improvement in exercise ability.

Administer orally twice daily. Dosing recommendations: - Patients >12 years of age and >40 kg: initial 62.5 mg twice daily for 4 weeks, then 125 mg twice daily. - Patients >12 years of age and <40 kg: 62.5 mg twice daily for 4 weeks, then 62.5 mg twice daily. - Patients ≤12 years of age: weight-based dosing: - ≥4-8 kg: 16 mg twice daily - >8-16 kg: 32 mg twice daily - >16-24 kg: 48 mg twice daily - >24-40 kg: 64 mg twice daily Doses above 125 mg twice daily did not appear to confer additional benefit sufficient to offset the increased risk of hepatotoxicity. Film-coated tablets and tablets for oral suspension (dispersible tablets) should be administered orally twice daily. Disperse tablets for oral suspension, or dispersible tablet half, in a minimal amount of water immediately before administration. Store divided dispersible tablet pieces at 20 ºC to 25 ºC (68 ºF to 77 ºF) in the opened blister for up to 7 days. Required monitoring: Healthcare professionals who prescribe Tracleer must enroll in the Bosentan REMS and must comply with the required monitoring. Measure liver aminotransferase levels prior to initiation of treatment and then monthly. Exclude pregnancy before initiating treatment with Tracleer in females of reproductive potential. Dosage adjustments for aminotransferase elevations: - >3 and ≤5 × ULN: Confirm by another aminotransferase test; if confirmed, in adults and pediatric patients >12 years and >40 kg, reduce the daily dose to 62.5 mg twice daily or interrupt treatment, and monitor aminotransferase levels at least every 2 weeks. If levels return to pretreatment values, treatment may continue or be reintroduced at 62.5 mg twice daily, with reassessment within 3 days. In all other pediatric patients, interrupt treatment with no prior dose reduction. If levels return to pretreatment values, reintroduce at the dose used prior to treatment interruption, with reassessment within 3 days. - >5 and ≤8 × ULN: Confirm by another aminotransferase test; if confirmed, stop treatment and monitor aminotransferase levels at least every 2 weeks. Once levels return to pretreatment values, in adults and pediatric patients >12 years and >40 kg, consider reintroduction at 62.5 mg twice daily, with reassessment within 3 days. In all other pediatric patients, consider reintroduction at the dose used prior to treatment interruption, with reassessment within 3 days. - >8 × ULN: Stop treatment permanently. There is no experience with reintroduction in these circumstances. Discontinue Tracleer if liver aminotransferase elevations are accompanied by clinical symptoms of hepatotoxicity (such as nausea, vomiting, fever, abdominal pain, jaundice, or unusual lethargy or fatigue) or bilirubin ≥2 × UL