Ambrisentan (U.S. trade name Letairis; E.U. trade name Volibris; India trade name Pulmonext by MSN labs) is a drug indicated for use in the treatment of pulmonary hypertension. The peptide endothelin constricts muscles in blood vessels, increasing blood pressure. Ambrisentan, which relaxes those muscles, is an endothelin receptor antagonist, and is selective for the type A endothelin receptor (ET_A). Ambrisentan significantly improved exercise capacity (6-minute walk distance) compared with placebo in two double-blind, multicenter trials (ARIES-1 and ARIES-2). Like all endothelin receptor antagonists, Ambrisentan is contraindicated in pregnant women as well as those who are trying to become pregnant, due to the potential for teratogenic effects on the fetus. Patients who are on the Ambrisentan must enroll in the Ambrisentan (Letairis) REMS Program. Ambrisentan was approved by the U.S. Food and Drug Administration (FDA) and the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...

(EMA), and designated an

orphan drug An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment of ...

, for the treatment of pulmonary hypertension.

Clinical uses

Ambrisentan is indicated for the treatment of pulmonary arterial hypertension (WHO Group 1) in patients with WHO class II or III symptoms to improve exercise capacity and delay clinical worsening.

Mechanism of action

Ambrisentan is a drug that blocks endothelin, an endogenous hormone found in higher quantities in patients with pulmonary arterial hypertension. Endothelin binds to two receptors, ET_A and ET_B. ET_A is responsible for cell growth in the vessels as well as vasoconstriction, while ET_B plays a role in vasodilation, endothelin 1 clearance, and anti

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of cells.

Birth defects

Endothelin receptor activation mediates strong pulmonary vasoconstriction and positive inotropic effect on the heart. These physiologic effects are vital for the development of the fetal cardiopulmonary system. In addition to this, endothelin receptors are also known to play a role in neural crest cell migration, growth, and differentiation. As such, endothelin receptor antagonists such as Ambrisentan are known to be teratogenic. Ambrisentan has a high risk of liver damage, and of birth defects if a woman becomes pregnant while taking it. In the U.S., doctors who prescribe it, and patients who take it, must enroll in a special program, the LETAIRIS Education and Access Program (LEAP), to learn about those risks. Ambrisentan is available only through specialty pharmacies.

Hepatic impairment

Ambrisentan is not recommended in patients with moderate or severe

hepatic impairment Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Signs and symptoms Some of the sig ...

. The medication should also be discontinued if the liver aminotransferase enzymes for the patients are increased more than fivefold, or if the elevations are more than twofold and are accompanied by changes in

bilirubin Bilirubin (BR) (Latin for "red bile") is a red-orange compound that occurs in the normal catabolic pathway that breaks down heme in vertebrates. This catabolism is a necessary process in the body's clearance of waste products that arise from the ...

Publications

References

External links

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