Sacubitril and Valsartan

ENTRESTO is a combination of sacubitril, a neprilisin inhibitor, and valsartan, an angiotensin II receptor blocker, and is indicated: to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure. Benefits are most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal. for the treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older. ENTRESTO reduces NT-proBNP and is expected to improve cardiovascular outcomes.

ENTRESTO contains a neprilysin inhibitor, sacubitril, and an angiotensin receptor blocker, valsartan. ENTRESTO inhibits neprilysin (neutral endopeptidase, NEP) via LBQ657, the active metabolite of the prodrug sacubitril, and blocks the angiotensin II type-1 (AT 1 ) receptor via valsartan. The cardiovascular and renal effects of ENTRESTO in heart failure patients are attributed to the increased levels of peptides that are degraded by neprilysin, such as natriuretic peptides, by LBQ657, and the simultaneous inhibition of the effects of angiotensin II by valsartan. Valsartan inhibits the effects of angiotensin II by selectively blocking the AT 1 receptor, and also inhibits angiotensin II-dependent aldosterone release.

The recommended starting dosage for adults is 49 mg/51 mg orally twice daily. The target maintenance dose is 97 mg/103mg orally twice daily. Adjust adult doses every 2 to 4 weeks to the target maintenance dose, as tolerated by the patient. For pediatric patients, see the Full Prescribing Information for recommended dosage, titrations, preparation and administration instructions. Reduce starting dose to half the usually recommended starting dosage for: patients not currently taking an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) or previously taking a low dose of these agents. patients with severe renal impairment. patients with moderate hepatic impairment.

ENTRESTO is contraindicated: in patients with hypersensitivity to any component in patients with a history of angioedema related to previous ACE inhibitor or ARB therapy with concomitant use of ACE inhibitors. Do not administer within 36 hours of switching from or to an ACE inhibitor with concomitant use of aliskiren in patients with diabetes Hypersensitivity to any component. History of angioedema related to previous ACEi or ARB therapy. Concomitant use with ACE inhibitors. Concomitant use with aliskiren in patients with diabetes.

Boxed warning (fetal toxicity): When pregnancy is detected, discontinue ENTRESTO 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 angioedema and hypotension. Monitor renal function and potassium in susceptible patients.

Clinically significant adverse reactions that appear in other sections of the labeling include: Angioedema Hypotension Impaired Renal Function Hyperkalemia Adverse reactions occurring greater than or equal to 5% are hypotension, hyperkalemia, cough, dizziness, and renal failure.

Avoid concomitant use with aliskiren in patients with estimated glomerular filtration rate (eGFR) less than 60. Potassium-sparing diuretics: May lead to increased serum potassium. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): May lead to increased risk of renal impairment. Lithium: Increased risk of lithium toxicity.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F). Protect from moisture.