What to Know About Entresto (sacubitril/valsartan)

A combination medication for heart failure

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Entresto (sacubitril/valsartan) is a medication that's prescribed for treating chronic heart failure in adults and certain types of heart failure in children over age 1. Approved by the Food and Drug Administration on July 7, 2015, with an expansion of its indication in 2021, Entresto belongs to a class of drugs known as angiotensin receptor neprilysin inhibitors (ARNIs). It combines two medications—valsartan, which also is prescribed independently to treat heart failure (under the brand name Diovan), and sacubitril, which can be found only in Entresto. Most people take Entresto as a pill, but it can be formulated as a liquid for children and adults who are unable to swallow pills.

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Uses

Entresto is approved to treat:

  • Adults who have class II, III, or IV heart failure with a reduced ejection fraction (HFrEF).
  • Adults who have heart failure with preserved ejection fraction (HFpEF).
  • Children over age 1 who have left ventricular systolic dysfunction and are experiencing symptoms of the condition.

Heart failure involves mild to severe limitations of activity and varying degrees of symptoms and discomfort at rest and/or with activity. The goal of treatment is to reduce the need for hospitalization and death from chronic heart failure.

In studies of adults, Entresto has been found to be superior to other heart failure medications in reducing hospitalization and death from chronic heart failure. In a study of more than 8,000 people with heart failure, the drug was shown to help people live longer and out of the hospital compared to Enalapril, another leading heart failure medication.

The two active ingredients in Entresto lower blood pressure via different mechanisms:

  • Valsartin, an angiotensin II receptor blocker (ARB), prevents blood vessels from narrowing by blocking the actions of certain enzymes and peptides, thereby reducing blood pressure and improving blood flow.
  • Sacubitril, a neprilysin inhibitor, raises the levels of several peptides (small proteins) that have beneficial effects on blood flow in patients with heart failure.

Entresto typically is prescribed along with other heart failure medications in place of either another ARB or instead of an angiotensin-converting enzyme (ACE) inhibitor.

Before Taking

Your healthcare provider may prescribe Entresto for you if you have a low ejection fraction and are experiencing symptoms such as pain during exercise or at rest or limitations in your physical activity due to heart failure. It also may be prescribed if you've been hospitalized for heart failure in the previous 12 months.

Before you being taking Entresto, make sure your healthcare provider is up-to-date on your medical history. Of particular concern:

  • Any chronic medical conditions, especially involving your kidneys or liver
  • A history of allergies that trigger hives and swelling

Your healthcare provider also needs to know about all prescription, over-the-counter medications, and nutritional supplements that you take—including but not limited to:

If you are taking an ACE inhibitor, you will need to stop taking it and wait at least 36 hours before you can start Entresto.

Precautions and Contraindications

Entresto may not be safe for you if you:

  • Are allergic to sacubitril or valsartan
  • Have had an allergic reaction (symptom such as swelling of your face, lips, tongue, or throat or trouble breathing) to an ACE inhibitor or ARB. It has been found that people who are Black are more likely to have such a reaction to Entresto.
  • Have diabetes and take Tekturna (aliskiren) or a medication that contains aliskiren

Entresto can harm a developing baby. If you are pregnant or plan to be, or if you are breastfeeding, you should not take this medication unless there is no alternative and your healthcare provider determines that the benefits outweigh the risk to your child. Likewise, if you become pregnant while already taking Entresto, tell your healthcare provider right away so they can find a safer medication for you.

Entresto does not have a long history of use, so little is known about how it might affect conditions such as Alzheimer's disease or prostate cancer.

While taking Entresto, you should not use salt substitutes containing potassium.

Dosage

Entresto comes as a film-coated tablet in three doses:

  • 24 milligrams (mg) of sacubitril/26 mg of valsartan
  • 49 mg of sacubitril/51 mg of valsartan
  • 97 mg of sacubitril/103 mg of valsartan

The manufacturer advises adults start with the middle dose of 49/26 mg and increase to 97/103 mg after two to four weeks if the drug is tolerated well.

All listed dosages are according to the drug manufacturer. Check your prescription and talk to your healthcare provider to make sure you are taking the right dose for you.

Modifications

The manufacturer further advises that children be given the liquid form of Entresto twice a day, in doses based on body weight, also starting with a low dose and advancing to a higher dose if needed and if it is well tolerated.

How to Take and Store

You can take Entresto with food or on an empty stomach. Take each dose at the same time each day. If you forget a dose, take it as soon as you realize you missed it unless it's nearly time for your next dose, in which case wait until then. When giving liquid Entresto to a child, shake the bottle before measuring out the dose.

Entresto should be kept in the container it came in, tightly closed, and out of sight and reach of children. Store tablets at room temperature and away from excess heat and moisture (not in the bathroom). Store liquid Entresto at room temperature for up to 15 days; do not refrigerate it.

Side Effects

As with any medication, Entresto can have side effects.

Common

  • Cough
  • Extreme fatigue
  • Dizziness, lightheadedness, and fainting after getting up too quickly from a prone position
  • Increased potassium levels

Severe

  • Angioedema, which is a rash, itching, or swelling of the tongue, throat or face, causing trouble breathing and death
  • Low blood pressure (hypotension)
  • Kidney problems

Warnings and Interactions

You should not take Entresto if you are taking an ACE inhibitor or an ARB, or if you've ever had an allergic reaction with swelling to an ACE inhibitor or ARB therapy.

Heart Failure Healthcare Provider Discussion Guide

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