كاندلكان 16مجم 14 قرص

12.1 Mechanism of Action 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. Candesartan has much greater affinity (>10,000-fold) for the AT 1 receptor than for the AT 2 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 also catalyzed by ACE. Because candesartan does not inhibit ACE (kininase II), it does not affect the response to bradykinin. Whether this difference has clinical relevance is not yet known. Candesartan does not bind to or block other hormone 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 candesartan on blood pressure.

Candesartan cilexetil tablets are 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 (1.1). · Treatment of heart failure (NYHA class II-IV); candesartan cilexetil tablets reduces cardiovascular death and heart failure hospitalization (1.2) 1.1 Hypertension Candesartan cilexetil tablets are indicated for the treatment of hypertension in adults and in 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. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit....

Starting Dose Target Dose Adult Hypertension (2.1) 16 mg tablet once daily 8 to 32 mg tablet total daily dose Pediatric Hypertension (1 to ˂6 years) (2.2) 0.2 mg/kg oral suspension once daily 0.05 to 0.4 mg/kg oral suspension once daily or consider divided dose Pediatric Hypertension (6 to ˂17 years) (2.2) <50 kg 4 to 8 mg tablet once daily >50 kg 8 to 16 mg tablet once daily <50 kg 4 to 16 mg tablet once daily or consider divided dose >50 kg 4 to 32 mg tablet once daily or consider divided dose Adult Heart Failure (2.3) 4 mg tablet once daily 1 The target dose is 32 mg once daily, which is achieved by doubling the dose at approximately 2-week intervals, as tolerated by patient 2.1 Adult Hypertension Dosage must be individualized. Blood pressure response is dose related over the range of 2 to 32 mg. The usual recommended starting dose of candesartan cilexetil tablet is 16 mg once daily when it is used as monotherapy in patients who are not volume depleted. Candesartan cilexetil tablets can be administered once or twice daily with total daily doses ranging from 8 mg to 32 mg. Larger doses do not appear to have a greater effect, and there is relatively little experience with such doses. Most of the antihypertensive effect is present within 2 weeks, and maximal blood pressure reduction is generally obtained within 4 to 6 weeks of treatment with candesartan cilexetil tablets. Use in Hepatic Impairment: Initiate with 8 mg candesartan cilexetil tablets in patients with moderate hepatic insufficiency. Dosing recommendations cannot be provided for patients with severe hepatic insufficiency [see Clinical Pharmacology (12.3)] . Candesartan cilexetil tablets may be administered with or without food. If blood pressure is not controlled by candesartan cilexetil tablets alone, a diuretic may be added. Candesartan cilexetil tablets may be administered with other antihypertensive agents. 2.2 Pediatric Hypertension 1 to <17 Years of Age Candesartan cilexetil tablets may be administered once daily or divided into two equal doses. Adjust the dosage according to blood pressure response. For patients with possible depletion of intravascular volume (e.g., patients treated with diuretics, particularly those with impaired renal function), initiate candesartan cilexetil tablets under close medical supervision and consider administration of a lower dose [see (5.3)]. Children 1 to <6 years of age: The dose range is 0.05 to 0.4 mg/kg per day. The recommended starting dose is 0....

· Most common which caused adult patients to discontinue therapy for: o Hypertension were headache (0.6%) and dizziness (0.3%) (6.1). o Heart Failure were hypotension (4.1%) (5.3), abnormal renal function (6.3%) (5.4), and hyperkalemia (2.4%) (5.5). To report SUSPECTED , contact Alembic Pharmaceuticals Limited at 1-866-210-9797 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. Adult Hypertension Candesartan cilexetil has been evaluated for safety in more than 3600 patients/subjects, including more than 3200 patients treated for hypertension. About 600 of these patients were studied for at least 6 months and about 200 for at least 1 year. In general, treatment with candesartan cilexetil was well tolerated. The overall incidence of adverse events reported with candesartan cilexetil was similar to placebo. The rate of withdrawals due to adverse events in all trials in patients (7510 total) was 3.3% (i.e., 108 of 3260) of patients treated with candesartan cilexetil as monotherapy and 3.5% (i.e., 39 of 1106) of patients treated with placebo. In placebo- controlled trials, discontinuation of therapy due to clinical adverse events occurred in 2.4% (i.e., 57 of 2350) of patients treated with candesartan cilexetil and 3.4% (i.e., 35 of 1027) of patients treated with placebo. The most common reasons for discontinuation of therapy with candesartan cilexetil were headache (0.6%) and dizziness (0.3%). The adverse events that occurred in placebo-controlled clinical trials in at least 1% of patients treated with candesartan cilexetil and at a higher incidence in candesartan cilexetil (n = 2350) than placebo (n = 1027) patients included back pain (3% vs. 2%), dizziness (4% vs. 3%), upper respiratory tract infection (6% vs. 4%), pharyngitis (2% vs. 1%), and rhinitis (2% vs. 1%). Pediatric Hypertension Among children in clinical studies, 1 in 93 children age 1 to <6 and 3 in 240 age 6 to <17 experienced worsening renal disease. The association between candesartan and exacerbation of the underlying condition could not be excluded....

Candesartan cilexetil tablets are contraindicated in patients who are hypersensitive to candesartan. Do not co-administer aliskiren with candesartan cilexetil tablets in patients with diabetes [see (7.4)]. Known hypersensitivity to product components (4). Do not co-administer aliskiren with candesartan cilexetil tablets in patients with diabetes (4).