زيستريل 5مجم 10 اقراص

12.1 Mechanism of Action Lisinopril inhibits angiotensin-converting enzyme (ACE) in human subjects and animals. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex. The beneficial effects of lisinopril in hypertension and heart failure appear to result primarily from suppression of the renin-angiotensin-aldosterone system. Inhibition of ACE results in decreased plasma angiotensin II which leads to decreased vasopressor activity and to decreased aldosterone secretion. The latter decrease may result in a small increase of serum potassium. In hypertensive patients with normal renal function treated with Zestril alone for up to 24 weeks, the mean increase in serum potassium was approximately 0.1 mEq/L; however, approximately 15% of patients had increases greater than 0.5 mEq/L and approximately 6% had a decrease greater than 0.5 mEq/L. In the same study, patients treated with Zestril and hydrochlorothiazide for up to 24 weeks had a mean decrease in serum potassium of 0.1 mEq/L; approximately 4% of patients had increases greater than 0.5 mEq/L and approximately 12% had a decrease greater than 0.5 mEq/L [see Clinical Studies (14.1) ] . Removal of angiotensin II negative feedback on renin secretion leads to increased plasma renin activity. ACE is identical to kininase, an enzyme that degrades bradykinin. Whether increased levels of bradykinin, a potent vasodepressor peptide, play a role in the therapeutic effects of Zestril remains to be elucidated. While the mechanism through which Zestril lowers blood pressure is believed to be primarily suppression of the renin-angiotensin-aldosterone system, Zestril is antihypertensive even in patients with low-renin hypertension. Although Zestril was antihypertensive in all races studied, Black hypertensive patients (usually a low-renin hypertensive population) had a smaller average response to monotherapy than non Black patients. Concomitant administration of Zestril and hydrochlorothiazide further reduced blood pressure in Black and non-Black patients and any racial differences in blood pressure response were no longer evident.

Zestril is an angiotensin converting enzyme (ACE) inhibitor indicated for: Treatment of hypertension in adults and pediatric patients 6 years of age and older ( 1.1 ) Adjunct therapy for heart failure ( 1.2 ) Treatment of Acute Myocardial Infarction ( 1.3 ) 1.1 Hypertension Zestril is indicated for the treatment of hypertension in adult patients and pediatric patients 6 years of age and older to lower blood pressure. Lowering blood pressure lowers 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. 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 1 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. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal....

Hypertension: Initial adult dose is 10 mg once daily. Titrate up to 40 mg daily based on blood pressure response. Initiate patients on diuretics at 5 mg once daily ( 2.1 ) Pediatric patients with glomerular filtration rate > 30 mL/min/1.73m 2 : Initial dose in patients 6 years of age and older is 0.07 mg per kg (up to 5 mg total) once daily ( 2.1 ) Heart Failure: Initiate with 5 mg once daily. Increase dose as tolerated to 40 mg daily ( 2.2 ) Acute Myocardial Infarction (MI): Give 5 mg within 24 hours of MI. Followed by 5 mg after 24 hours, then 10 mg once daily ( 2.3 ) Renal Impairment: For patients with creatinine clearance ≥ 10 mL/min and ≤ 30 mL/min, halve usual initial dose. For patients with creatinine clearance < 10 mL/min or on hemodialysis, the recommended initial dose is 2.5 mg ( 2.4 ) 2.1 Hypertension Initial Therapy in adults: The recommended initial dose is 10 mg once a day. Dosage should be adjusted according to blood pressure response. The usual dosage range is 20 mg to 40 mg per day administered in a single daily dose. Doses up to 80 mg have been used but do not appear to give greater effect. Use with diuretics in adults If blood pressure is not controlled with Zestril alone, a low dose of a diuretic may be added (e.g., hydrochlorothiazide, 12.5 mg). After the addition of a diuretic, it may be possible to reduce the dose of Zestril. The recommended starting dose in adult patients with hypertension taking diuretics is 5 mg once per day. Pediatric Patients 6 years of age and older with hypertension For pediatric patients with glomerular filtration rate > 30 mL/min/1.73m 2 , the recommended starting dose is 0.07 mg per kg once daily (up to 5 mg total). Dosage should be adjusted according to blood pressure response up to a maximum of 0.61 mg per kg (up to 40 mg) once daily. Doses above 0.61 mg per kg (or in excess of 40 mg) have not been studied in pediatric patients [see Clinical Pharmacology (12.3) ] . Zestril is not recommended in pediatric patients < 6 years or in pediatric patients with glomerular filtration rate < 30 mL/min/1.73m 2 [see (8.4) and Clinical Studies (14.1) ] . 2.2 Heart Failure The recommended starting dose for Zestril, when used with diuretics and (usually) digitalis as adjunctive therapy for systolic heart failure, is 5 mg once daily. The recommended starting dose in these patients with hyponatremia (serum sodium < 130 mEq/L) is 2.5 mg once daily. Increase as tolerated to a maximum of 40 mg once daily....

Common (events 2% greater than placebo) by use: Hypertension: headache, dizziness and cough ( 6.1 ) Heart Failure: hypotension and chest pain ( 6.1 ) Acute Myocardial Infarction: hypotension ( 6.1 ) To report SUSPECTED , contact Upsher-Smith Laboratories, LLC at 1-855-899-9180 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials 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. Hypertension In clinical trials in patients with hypertension treated with Zestril, 5.7% of patients on Zestril discontinued with . The following (events 2% greater on Zestril than on placebo) were observed with Zestril alone: headache (by 3.8%), dizziness (by 3.5%), cough (by 2.5%). Heart Failure In patients with systolic heart failure treated with Zestril for up to four years, 11% discontinued therapy with . In controlled studies in patients with heart failure, therapy was discontinued in 8.1% of patients treated with Zestril for 12 weeks, compared to 7.7% of patients treated with placebo for 12 weeks. The following (events 2% greater on Zestril than on placebo) were observed with Zestril: hypotension (by 3.8%), chest pain (by 2.1%). In the two-dose ATLAS trial [see Clinical Studies (14.2) ] in heart failure patients, withdrawals due to were not different between the low and high groups, either in total number of discontinuation (17% to 18%) or in rare specific reactions (< 1%). The following , mostly related to ACE inhibition, were reported more commonly in the high dose group: Table 1 Dose-related Adverse Drug Reactions: ATLAS trial High Dose (n=1568) Low Dose (n=1596) Dizziness 19% 12% Hypotension 11% 7% Creatinine increased 10% 7% Hyperkalemia 6% 4% Syncope 7% 5% Acute Myocardial Infarction Patients treated with Zestril had a higher incidence of hypotension (by 5.3%) and renal dysfunction (by 1.3%) compared with patients not taking Zestril. Other clinical occurring in 1% or higher of patients with hypertension or heart failure treated with Zestril in controlled clinical trials and do not appear in other sections of labeling are listed below: Body as a whole : Fatigue, asthenia, orthostatic effects. Digestive : Pancreatitis, constipation, flatulence, dry mouth, diarrhea....

Zestril is contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril). Do not administer Zestril within 36 hours of switching to or from sacubitril/valsartan, a neprilysin inhibitor [ see (5.2)] . Zestril is contraindicated in patients with: a history of angioedema or hypersensitivity related to previous treatment with an angiotensin converting enzyme inhibitor hereditary or idiopathic angioedema Do not co-administer aliskiren with ZESTRIL in patients with diabetes [see (7.4) ] . Angioedema or a history of hereditary or idiopathic angioedema ( 4 ) Hypersensitivity ( 4 ) Co-administration of aliskiren with Zestril in patients with diabetes ( 4 , 7.4 )