What Are Sacubitril/Valsartan (Entresto)?

Reviewed by: HU Medical Review Board | Last reviewed: November 2019 | Last updated: March 2023

Sacubitril/valsartan, known by the brand name Entresto,® is an Angiotensin-Receptor Neprilysin Inhibitor (ARNI). It is a new drug combining a neprilysin inhibitor and an angiotensin II receptor blocker (ARB).1-2 Sacubitril/valsartan 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.2

Sacubitril/valsartan helps lower the risk of hospitalization and death from worsening heart failure symptoms.1-2 It is prescribed in place of an ACE inhibitor/ARB.2 It is also indicated for the treatment of symptomatic heart failure with left ventricular systolic dysfunction in children over age one.2

What are the ingredients in sacubitril/valsartan?

The active ingredients are sacubitril and valsartan.2

How does sacubitril/valsartan work?

The drug combination contains sacubitril and valsartan, two medicines that work in different ways. Valsartan is an ARB that has been used in heart failure treatment for years. Angiotensin II receptor blockers (ARBs) are a type of vasodilator, a drug that widens blood vessels to lower blood pressure, improve blood flow, and decrease the workload on the heart.1-3 They do this by blocking angiotensin II, a hormone in the body that acts as a vasoconstrictor, causing the blood vessels to narrow (constrict).

Sacubitril is a new medicine that is only found in the Entresto brand. Sacubitril is a neprilysin inhibitor that prevents the breakdown of certain vasoactive peptides in the body causing the blood vessels to widen. Together the medicines work to relax blood vessels and improve blood flow to help a weakened and enlarged heart to pump more effectively.1-2

What are the possible side effects of sacubitril/valsartan?

Any medication has possible adverse effects, and it’s important to be aware of the potential side effects when starting a new drug. Common side effects include coughing, dizziness, and lightheadedness. Some people experience lower blood pressure (hypotension), increased potassium (hyperkalemia), and increased serum creatinine levels. This is not a complete list of side effects.1-3

Things to know about sacubitril/valsartan

Sacubitril/valsartan is available as film-coated tablets and as an oral suspension. Tablets come in three strengths.2

They can contain:

  • 24 mg of sacubitril and 26 mg of valsartan
  • 49 mg of sacubitril and 51 mg of valsartan
  • 97 mg of sacubitril and 103 mg of valsartan

An oral suspension can be prepared by a pharmacist for patients unable to swallow tablets.1-2

Sacubitril/valsartan has been shown to reduce HF hospitalizations and death better than ACE inhibitors. They can also improve heart function or delay the progression of heart failure, reduce symptoms, and help people feel better.

You should not take sacubitril and valsartan if you are allergic to sacubitril or valsartan or any of its ingredients. If you have had a prior severe allergic reaction to ACE inhibitors or ARBs discuss this with your doctor before starting on sacubitril/valsartan.1-2

Be sure to tell the doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Different medicines can interact with each other and may affect the way they work or cause serious side effects.1-2

Do not take sacubitril/valsartan if you take an ACE inhibitor. If your doctor recommends that you switch from an ACE inhibitor to sacubitril/valsartan make sure to wait 36 hours between taking the two drugs to avoid any drug interactions.2

Talk to your doctor before starting sacubitril/valsartan if you:1-2

  • are pregnant or planning to become pregnant
  • have diabetes, especially if you take the medication aliskiren
  • have kidney or liver disease
  • hereditary angioedema
  • take potassium supplements
  • take nonsteroidal anti-inflammatory drugs (NSAIDs) or lithium
  • are breastfeeding

Dosing information

The recommended starting dose of sacubitril/valsartan is 49/51 mg orally twice a day. The dose is typically doubled after 2 to 4 weeks until achieving the maintenance dose of 97/103 mg twice daily, as tolerated.2 An oral suspension can be substituted at the recommended dosage in patients unable to swallow tablets.1-2

Dose Adjustments can be prescribed for adults and children with severe renal impairment, moderate hepatic impairment and for patients not currently taking an ACE or an ARB.1-2

Sacubitril/valsartan should be stored at room temperature. Bottles should be kept tightly closed and protected from light.2 The oral suspension can be stored for up to 15 days. It should be stored at room temperature and not be refrigerated. Shake before each use.

For more information, read the full prescribing information of sacubitril/valsartan.

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