Angiotensin II [formed from angiotensin I in a reaction catalyzed by angiotensin converting enzyme (ACE, kininase II)] is a potent vasoconstrictor, the primary vasoactive hormone of the renin-angiotensin system, and an important component in the pathophysiology of hypertension. It also stimulates aldosterone secretion by the adrenal cortex. Losartan and its principal active metabolite block the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT receptor found in many tissues, (e.g., vascular smooth muscle, adrenal gland). There is also an AT receptor found in many tissues but it is not known to be associated with cardiovascular homeostasis. Neither losartan nor its principal active metabolite exhibits any partial agonist activity at the AT receptor, and both have much greater affinity (about 1000-fold) for the AT receptor than for the AT receptor. In vitro binding studies indicate that losartan is a reversible, competitive inhibitor of the AT receptor. The active metabolite is 10 to 40 times more potent by weight than losartan and appears to be a reversible, non competitive inhibitor of the AT receptor. Neither losartan nor its active metabolite inhibits ACE (kininase II, the enzyme that converts angiotensin I to angiotensin II and degrades bradykinin), nor do they bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.

COZAAR is an angiotensin II receptor blocker (ARB) indicated for:

• Treatment of hypertension, to lower blood pressure in adults and children greater than 6 years old.
  Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. 
• Reduction of the risk of stroke in patients with hypertension and left ventricular hypertrophy. There is evidence that this benefit does not apply to Black patients. 
• Treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria in patients with type 2 diabetes and a history of hypertension. 

Hypertension

• Usual adult dose: 50 mg once daily. 
• Usual pediatric starting dose: 0.7 mg per kg once daily (up to 50 mg). 

Hypertensive Patients with Left Ventricular Hypertrophy

• Usual starting dose: 50 mg once daily.
• Add hydrochlorothiazide 12.5 mg and/or increase COZAAR to 100 mg followed by an increase to hydrochlorothiazide 25 mg if further blood pressure response is needed.

Nephropathy in Type 2 Diabetic Patients

• Usual dose: 50 mg once daily.
• Increase dose to 100 mg once daily if further blood pressure response is needed.

Most common adverse reactions (incidence ≥2% and greater than placebo) are: dizziness, upper respiratory infection, nasal congestion, and back pain.

Hypersensitivity to any component.
Coadministration with aliskiren in patients with diabetes.

Hypotension: Correct volume or salt depletion prior to administration of COZAAR.
Monitor renal function and potassium in susceptible patients.