Tap below to see additional Important Safety Information and full Prescribing Information, including Boxed WARNING.
Prescribing Information, including Boxed WARNING
Important Safety Information
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INDICATION

ENTRESTO 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.

LVEF is a variable measure, so use clinical judgment in deciding whom to treat.

IMPORTANT SAFETY INFORMATION

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

ENTRESTO is contraindicated in patients with hypersensitivity to any component. ENTRESTO is contraindicated in patients with a history of angioedema related to previous angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy.

ENTRESTO is contraindicated with concomitant use of ACE inhibitors. Do not administer within 36 hours of switching from or to an ACE inhibitor. ENTRESTO is contraindicated with concomitant use of aliskiren in patients with diabetes.

Angioedema: ENTRESTO may cause angioedema. Angioedema associated with laryngeal edema may be fatal. ENTRESTO has been associated with a higher rate of angioedema in Black patients and in patients with a prior history of angioedema. ENTRESTO should not be used in patients with hereditary angioedema. If angioedema occurs, discontinue ENTRESTO immediately, provide appropriate therapy, and monitor for airway compromise. ENTRESTO must not be re‑administered.

Hypotension: ENTRESTO lowers blood pressure and may cause symptomatic hypotension. Patients with an activated renin-angiotensin system, such as volume- and/or salt-depleted patients (e.g., those being treated with high doses of diuretics), are at greater risk. Correct volume or salt depletion prior to administration of ENTRESTO or start at a lower dose. If hypotension persists despite dose adjustment of diuretics, concomitant antihypertensive drugs, and treatment of other causes of hypotension (e.g., hypovolemia) reduce the dosage or temporarily discontinue ENTRESTO. Permanent discontinuation of therapy is usually not required.

Impaired Renal Function: Decreases in renal function may be anticipated in susceptible individuals treated with ENTRESTO. In patients whose renal function depends upon the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe congestive heart failure), treatment with ACE inhibitors and angiotensin receptor antagonists has been associated with oliguria, progressive azotemia and, rarely, acute renal failure and death. Closely monitor serum creatinine, and down-titrate or interrupt ENTRESTO in patients who develop a clinically significant decrease in renal function.

ENTRESTO may increase blood urea and serum creatinine levels in patients with bilateral or unilateral renal artery stenosis. In patients with renal artery stenosis, monitor renal function. Avoid use with aliskiren in patients with renal impairment (eGFR <60 mL/min/1.73 m2).

In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs), including COX-2 inhibitors, with ENTRESTO may result in worsening of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically.

Hyperkalemia: Hyperkalemia may occur with ENTRESTO. Monitor serum potassium periodically and treat appropriately, especially in patients with risk factors for hyperkalemia such as severe renal impairment, diabetes, hypoaldosteronism, or a high potassium diet. Dosage reduction or interruption of ENTRESTO may be required.

Concomitant use of potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium, may lead to increases in serum potassium.

ARBs: Avoid use of ENTRESTO with an ARB, because ENTRESTO contains the angiotensin II receptor blocker valsartan.

Lithium: Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists. Monitor serum lithium levels during concomitant use with ENTRESTO.

Common Adverse Events: In a clinical trial of patients with heart failure with reduced ejection fraction, the most commonly observed adverse events with ENTRESTO vs enalapril, occurring at a frequency of at least 5% in either group, were hypotension (18%, 12%), hyperkalemia (12%, 14%), cough (9%, 13%), dizziness (6%, 5%), and renal failure/acute renal failure (5%, 5%). No new adverse reactions were identified in a trial of the remaining indicated population.

Tap to bookmark page QUICK REFERENCE Initiation and Dosing

YOU CAN MAKE A DIFFERENCE NOW — START ENTRESTO®
IN THE HOSPITAL

A first-choice treatment for stabilized HF patients1,2

HF=heart failure.

INDICATION

ENTRESTO 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.

LVEF is a variable measure, so use clinical judgment in deciding whom to treat.

IMPORTANT SAFETY INFORMATION

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

GETTING ADULT PATIENTS WITH HF STARTED ON ENTRESTO® IN THE HOSPITAL

 

Dosing information1:

  • Dose options are 24/26 mg, 49/51 mg, or 97/103 mg administered twice daily. Dose should be titrated up after 2-4 weeks as tolerated by the patient, up to target dose of 97/103 mg twice daily. Recommended starting dose is 49/51 mg twice daily for patients currently taking a high-dose ACEi or ARB†

Additional dosing considerations1:

  • If patient is on an ACEi, stop using it for 36 hours (1.5 days) before starting ENTRESTO
  • Correct volume or salt depletion prior to administration of ENTRESTO or start at a lower dose

Use a starting dose of 24/26 mg twice daily for1:

  • Patients not currently taking an ACEi or ARB or previously taking a low dose of those agents‡
  • Patients with severe renal or moderate hepatic impairment

ENTRESTO is contraindicated with concomitant use of an ACEi and in patients with a history of angioedema related to previous ACEi or ARB therapy. Please see Prescribing Information for additional dosing recommendations.

ACEi=angiotensin-converting enzyme inhibitor; ADHF=acute decompensated heart failure; ARB=angiotensin II receptor blocker; BP=blood pressure; EF=ejection fraction; HFrEF=heart failure with reduced ejection fraction; IV=intravenous; LVEF=left ventricular ejection fraction.

*Multicenter, randomized, double-blind trial of in-hospital initiation of ENTRESTO (n=440) compared with enalapril (n=441) among HF patients with reduced EF (LVEF ≤40%) who had been stabilized following admission for ADHF in the US.

†High-dose ACEi: total daily dose of >10 mg of enalapril or therapeutically equivalent dose of another ACEi. High-dose ARB: total daily dose of >160 mg of valsartan or therapeutically equivalent dose of another ARB.4

‡Low-dose ACEi: total daily dose of ≤10 mg of enalapril or therapeutically equivalent dose of another ACEi. Low-dose ARB: total daily dose of ≤160 mg of valsartan or therapeutically equivalent dose of another ARB.4

Inititate Entresto in the hospital
 

References: 1. ENTRESTO [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; February 2021. 2. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017;136(6):e137-e161. 3. Velazquez EJ, Morrow DA, DeVore AD, et al; for the PIONEER-HF Investigators. Angiotensin–neprilysin inhibition in acute decompensated heart failure. N Engl J Med. 2019;380(6):539-548. 4. Senni M, McMurray JJV, Wachter R, et al. Initiating sacubitril/valsartan (LCZ696) in heart failure: results of TITRATION, a double-blind, randomised comparison of two uptitration regimens. Eur J Heart Fail. 2016;18(9)(suppl):1193-1202. doi:10.1002/ejhf.548. Accessed January 4, 2021. Supplementary material accessed at https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Fejhf.548&file=ejhf548-sup-0001-AppendixS1.doc

If you have any questions relating to this communication from Novartis Pharmaceuticals Corporation, please call 1-888-NOW-NOVA (1-888-669-6682), Monday through Friday, 8:30 AM to 5:00 PM ET. You may also submit your question in writing to: Novartis Pharmaceuticals Corporation, One Health Plaza, Customer Interaction Center, East Hanover, NJ 07936-1080.

ENTRESTO and the ENTRESTO logo are registered trademarks of Novartis AG.

Novartis Pharmaceuticals Corporation
East Hanover, New Jersey 07936-1080

© 2021 Novartis

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