Candesartan cilexetil

ATACAND is an angiotensin II receptor blocker (ARB) indicated for: • Treatment of hypertension in adults and children 1 to < 17 years of age, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions. • Treatment of heart failure (NYHA class II-IV), ATACAND reduces cardiovascular death and heart failure hospitalization.

Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase 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. Candesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT 1 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. There is also an AT 2 receptor found in many tissues, but AT 2 is not known to be associated with cardiovascular homeostasis.

Starting Dose Target Dose Adult Hypertension 16 mg tablet once daily 8 – 32 mg tablet total daily dose Pediatric Hypertension (1 to < 6 years) 0.20 mg/kg oral suspension once daily 0.05 – 0.4 mg/kg oral suspension once daily or consider divided dose Pediatric Hypertension (6 to < 17 years) < 50 kg 4 – 8 mg tablet once daily >50 kg 8 – 16 mg tablet once daily < 50 kg 4 – 16 mg tablet once daily or consider divided dose > 50 kg 4 – 32 mg tablet once daily or consider divided dose Adult Heart Failure 4 mg tablet once daily 32 mg tablet once daily The target dose is 32 mg once daily, which is achieved by doubling the dose at approximately 2-week intervals, as tolerated by patient.

ATACAND is contraindicated in patients who are hypersensitive to candesartan. Do not co-administer aliskiren with ATACAND in patients with diabetes. Known hypersensitivity to product components.

Boxed warning (fetal toxicity •): When pregnancy is detected, discontinue ATACAND as soon as possible. • Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. WARNING: FETAL TOXICITY • When pregnancy is detected, discontinue ATACAND as soon as possible. • Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. • Observe for signs and symptoms of hypotension. • Monitor renal function and potassium levels. Fetal Toxicity ATACAND can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations.

• Most common adverse reactions which caused adult patients to discontinue therapy for: • Hypertension were headache (0.6%) and dizziness (0.3%). • Heart Failure were hypotension (4.1%), abnormal renal function (6.3%), and hyperkalemia (2.4%).

• Lithium: Increases in serum lithium concentrations and toxicity. • NSAIDs use may lead to increased risk of renal impairment and loss of antihypertensive effect. • Combined inhibition of the renin-angiotensin system: Increased risk of renal impairment, hypotension, and hyperkalemia.

Storage Store at 20° to 25°C (68° to 77°F), excursions permitted at 15° to 30°C (59° to 86°F).