Azilsartan (EDARBI): A New Angiotensin Receptor Blocker (ARB) for Hypertension

Approved by the FDA for Marketing in the USA

Randa Hilal-Dandan


AccessMedicine from McGraw-Hill 

In This Article

Clinical Pharmacology

In the renin-angiotensin system, angiotensin II (AngII) is the principal vasoactive peptide that contributes to vasoconstriction, cardiac remodeling, aldosterone release, Na+ reabsorption in the renal tubules, and water retention. These effects of angiotensin II are primarily mediated via activation of the angiotensin II type 1 receptor (AT1). Azilsartan, the active moiety of the prodrug azilsartan medoxomil, is a highly selective AT1 receptor antagonist that inhibits these effects of AngII. Azilsartan medoxomil (20 mg, 40 mg, 80 mg) lowers the 24-hour mean systolic blood pressure in a dose-dependent manner.[4]

Azilsartan medoxomil was approved by the FDA based on the results of seven randomized, double blind, multicenter studies (6-24 weeks duration, involving over 5900 patients with hypertension) that demonstrated the significant antihypertensive effects of azilsartan medoxomil compared to placebo.[2,4,5,6] In one study on patients with primary hypertension, azilsartan medoxomil 80 mg showed superior efficacy in lowering 24-hour mean systolic BP (-14.3 mm Hg) compared to valsartan 320 mg (-10.0 mm Hg) and olmesartan 40 mg (-11.7 mm Hg).[5] The superior antihypertensive effect of azilsartan medoxomil 80 mg was not associated with any increase in adverse events when compared to maximal doses of the ARBs olmesartan 40 mg and valsartan 320 mg.[4,5,6] The 40 mg dose of azilsartan medoxomil was shown to have similar efficacy as olmesartan in lowering mean systolic blood pressure.[4,5]

In February of 2011, Takeda submitted a New Drug Application (NDA) for the investigational fixed-dose combination pill of azilsartan medoxomil (20 mg, 40 mg, and 80 mg) and the diuretic chlorthalidone (12.5 mg and 25 mg) for the treatment of hypertension.[7,8] The NDA was based on findings from four phase 3 clinical trials involving over 4000 patients with hypertension. The azilsartan medoxomil/chlorthalidone combination dose was reported to be superior to olmesartan/hydrochlorothiazide (HCTZ) in lowering blood pressure. The combination caused greater decreases in systolic BP compared to monotherapy with comparable doses of azilsartan medoxomil or olmesartan.[7]

On December 20, 2011, the FDA approved EDARBYCLOR (azilsartan medoxomil and chlorthalidone) for the treatment of hypertension. It is the only approved fixed-dose therapy in the US that combines an ARB with a diuretic. Fixed combination doses are available as 40/12.5 mg and 40/25 mg once-daily single tablets. The recommended starting dose is 40/12.5 mg and the maximum dose is 40/25 mg.[7]