ADVANT (Candesartan cilexetil) a prodrug is hydrolyzed to candesartanduring absorption from the gastrointestinal tract. Candesartan is a selective AT1 sub-type angiotensin II receptor antagonist. ADVANT Tablets 8 mg: Each tablet contains Candesartan cilexetil 8 mg. THERAPEUTIC INDICATIONS: Hypertension- ADVANT (Candesartan cilexetil) is indicated for the treatment of hypertension in adults and children 1 to < 17 years of age. It may be used alone or in combination with other antihypertensive agents. Heart Failure: -ADVANT (Candesartan cilexetil) is indicated for the treatment of heart failure (NYHA class II-IV) in adults with left ventricular systolic dysfunction(<40%) to reduce cardiovascular death and to reduce heart failurehospitalizations. ADVANT (Candesartan cilexetil) also has an added effect on these outcomes when used with an ACE inhibitor. MECHANISM OF ACTION: Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (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 re-absorption of sodium. Candesartan 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 pathways for angiotensin II synthesis. Candesartan cilexetil is rapidly converted to the active drug candesartan by ester hydrolysis during absorption from the gastrointestinal tract. Candesartan is an angiotensin II receptor antagonist selective for AT1receptors with tight binding to and slow dissociation from the receptor. It has no agonist activity. ACE inhibitors also inhibit the degradation of bradykinin a reaction also catalyzed by ACE. Because candesartan does not inhibit ACE (kinase II) it does not affect the response to bradykinin. Candesartan does not bind to or block other hormone receptors or ion channels known to be important in cardio vascular regulation. Blockade of the angiotensin II receptor inhibits the negative regulatoryfeedback of angiotensin II on renin secretion but the resulting increased plasma renin activity and angiotensin II circulating levels do not overcome the effect of candesartan on blood pressure.