EDARBI (azilsartan medoxomil) tablet

Azilsartan kamedoxomil is a white to nearly white powder with a molecular weight of 606.62. It is practically insoluble in water and freely soluble in methanol.

Edarbi is available for oral use as tablets. The tablets have a characteristic odor. Each Edarbi tablet contains 42.68 or 85.36 mg of azilsartan kamedoxomil, which is equivalent to containing 40 mg or 80 mg respectively, of azilsartan medoxomil and the following inactive ingredients: mannitol, fumaric acid, sodium hydroxide, hydroxypropyl cellulose, croscarmellose sodium, microcrystalline cellulose, and magnesium stearate.

Mechanism of Action
Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzymes (ACE, kinase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Azilsartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Its action is, therefore, independent of the pathway for angiotensin II synthesis.

An AT2 receptor is also found in many tissues, but this receptor is not known to be associated with cardiovascular homeostasis. Azilsartan has more than a 10,000-fold greater affinity for the AT1 receptor than for the AT2 receptor.

Blockade of the renin-angiotensin system with ACE inhibitors, which inhibit the biosynthesis of angiotensin II from angiotensin I, is widely used in the treatment of hypertension. ACE inhibitors also inhibit the degradation of bradykinin, a reaction catalyzed by ACE. Because azilsartan does not inhibit ACE (kinase II), it should not affect bradykinin levels. Whether this difference has clinical relevance is not yet known. Azilsartan does not bind to or block other receptors or ion channels known to be important in cardiovascular regulation.

Blockade of the angiotensin II receptor inhibits the negative regulatory feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and angiotensin II circulating levels do not overcome the effect of azilsartan on blood pressure.

USE IN SPECIFIC POPULATIONS
Nursing Mothers: Discontinue nursing or drug.

Geriatric Patients: Abnormally high serum creatinine values were more likely to be reported for patients age 75 or older. No overall difference in efficacy versus younger patients, but greater sensitivity of some older individuals cannot be ruled out.

In patients with an activated renin-angiotensin system, as by volume- or salt-depletion, renin-angiotensin-aldosterone system (RAAS) blockers such as azilsartan medoxomil can cause excessive hypotension. In susceptible patients, e.g., with renal artery stenosis, RAAS blockers can cause renal failure.

Pediatrics: Safety and efficacy in children have not been established.

To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals at 1-877-825-3327 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Edarbi may be administered with or without food.

Edarbi may be administered with other antihypertensive agents.

Edarbi is a trademark of Takeda Pharmaceutical Company Limited registered with the U.S. Patent and Trademark Office and used under license by Takeda Pharmaceuticals America, Inc.

©2011 Takeda Pharmaceuticals America, Inc.

April 2011