Ambrisentan for the treatment of pulmonary hypertension (PAH)

What is Ambrisentan?

Ambrisentan (brand named Letairis in the U.S., Volibris in the European Union and Canada) is an FDA-approved oral medication for the treatment of pulmonary hypertension. It is recommended by the FDA for patients with WHO class II and class III symptoms of pulmonary arterial hypertension (PAH) to improve exercise tolerance and slow down disease progression. The price for ambrisentan is over $10,000 per month in many countries, you can buy ambrisentan from our online pharmacy at an affordable price.

Ambrisentan is an endothelin receptor antagonist (ETA). It selectively inhibits the endothelin type-A (ETA) receptor. Endothelin-1 (ET-1) is a protein molecule our body makes for the purpose of cell to cell signaling. and ETA and ETB are receptors for ET-1 found on the smooth muscle cells of our blood vessels to mediate the effect of ET-1. When ET-1 binds with ETA  receptors, the blood vessels constrict, and blood pressure rises. When ET-1 binds with ETB receptors, the blood vessels dilate, and blood pressure drops.

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In patients with PAH, there is an estimated 10 fold increase of the ET-1 concentration in the blood and an increase in blood pressure indicates a rise in ETA receptor levels as well. In these cases, ambrisentan acts as the antagonist for ET-1 by binding more strongly to ETA receptors thus preventing ET-1 from binding with ETA receptors. By preventing ET-1 binding with ETA receptors, it also allows more ET-1 to bind with ETreceptors. The overall result is lessened blood vessel constriction coupled with increased blood vessel dilation leading to decreased blood pressure.

Ambrisentan (Letairis) Clinical Trials

Gilead, the manufacturer of Letairis in the United States, received FDA approval for the use of ambrisentan in pulmonary hypertension treatment in 2007 following successful results from their two main clinical trials, ARIES-1 and ARIES-2, both of which were 12-week, randomized, double-blind, placebo-controlled, multicenter studies.

Both the ARIES-1 and ARIES-2 trials were 12-week long, randomized, double-blinded, placebo-controlled, multicentre studies. Both studies compared the efficacy of PAH patients taking different dosages of ambrisentan at 2.5, 5, and 10mg to those who took placebo. The efficacy was measured by how well patients performed in the 6-minute walk distance (6MWD) test. Both studies produced convincing results that patients on ambrisentan had a significantly lowered disease progression rate compared to those who took placebo. Apart from these two studies, another major study, AMBITION, published more recently in 2015 showed that ambrisentan used in combination with tadalafil was more effective in improving patients’ life quality and slowing down disease progression than taking either medication alone.

Dosing for Ambrisentan

The recommended dosage for ambrisentan is 5 mg or 10 mg taken orally once daily. It is generally contraindicated in pregnancy, expecting mothers should seek expert advise regarding the use of ambrisentan during pregnancy. The most common side effects associated with ambrisentan include peripheral edema (swelling of the hands, feet, and lower legs), headache, nasal congestion, cough, flushing, bronchitis, sinusitis, loss of appetite.

 

 

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