Tracleer (bosentan) is an endothelin receptor antagonist (ERA) manufactured by Actelion Pharmaceuticals in the U.S., the European Union, and other countries. It is approved by the U.S. Food and Drug Administration (FDA) for the treatment of both adults and children with pulmonary arterial hypertension (PAH).

The drug is aimed at improving the ability of PAH patients to exercise and reduce disease progression by slowing clinical deterioration. 

How Tracleer works

Tracleer is a molecule that blocks the actions of endothelin-1 (ET-1), a protein that causes blood vessels to constrict. In healthy people, ET-1 helps maintain a balance between high and low blood pressure. However, patients with PAH produce too much ET-1, with abnormally high levels of ET-1 in both the bloodstream and inside the lining of blood vessels (the endothelium).

ET-1 exerts its effects on blood vessels by binding to one of two endothelin receptors — ETA or ETB. Tracleer binds to these receptors to block ET-1 from stimulating blood vessel constriction, which helps the vessels relax and increases blood flow to the lungs.

Tracleer in clinical trials

Tracleer was approved by the FDA to be used in adults with WHO functional classes 2 to 4 PAH in August 2009 based on the results of a Phase 3 clinical trial (NCT00091715) called EARLY. The results showed a considerable reduction in pulmonary vascular resistance (22.6 percent) and a 77 percent decrease in the clinical worsening in participants who were given Tracleer compared to placebo as measured by the six-minute walk test.

In September 2017, Tracleer was approved by the FDA to be used in children, making it the first FDA-approved medication for children with PAH. Indicated for patients ages 3 and older who have either idiopathic or congenital PAH, its approval was based on clinical studies that showed Tracleer is as safe and effective in children as it is for adults. 

A series of multicenter, open-label studies called FUTURE-1 (NCT00319267), FUTURE-2 (NCT00319020), and FUTURE-3 (NCT01338415) tested the safety and tolerability of Tracleer in children and established the drug’s optimum dose.

FUTURE-1 included 36 children who received 2 mg/kg of Tracleer twice a day for four weeks, followed by 4 mg/kg twice a day for eight weeks. Based on the results, published in the British Journal of Clinical Pharmacology in 2009, the authors concluded that a dose of 2 mg/kg twice a day achieved an acceptable risk/benefit profile.

FUTURE-2 and FUTURE-3 were extension studies that included children who completed FUTURE-1. They confirmed the long-term safety of Tracleer in children and continued to explore optimal dosing.

Other information

Tracleer is an oral formulation, available as 32 mg (for children), 62.5 mg, and 125 mg tablets. It should be taken with or without food, twice a day unless prescribed otherwise. Dosing in children is based on both the child’s weight and age, with doses for children younger than 12 ranging from 16 mg to 64 mg twice a day.  The 32 mg tablets can be broken in half and should be dissolved in water before being given to the child.

Patients with liver or kidney disease should consult a specialist before taking Tracleer, and the drug should not be used in those already taking drugs like Bosulif (bosutinib), Jevtana (cabazitaxel), Sandimmune (cyclosporine), or glyburide.

Tracleer can cause major birth defects if taken during pregnancy, so women of childbearing age must have a negative pregnancy test before starting treatment and use reliable forms of contraception during treatment. Liver toxicity and anemia are also potential side effects, so liver function and hematocrit should be monitored regularly during treatment.

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