Low Blood Pressure, Dizziness, and More: 5 Entresto Side Effects You Should Know About

Entresto (sacubitril / valsartan) was hailed as a “game-changer” for treating heart failure when it was first FDA approved in 2015. That’s because it was the first medication of its kind: a combination of an angiotensin II receptor blocker (valsartan) and neprilysin inhibitor (sacubitril). 

Over a decade later, Entresto is still a first-choice medication for treating heart failure. But like nearly all medications, it has potential side effects. Here’s what you should know.

Entresto side effects at a glance

Entresto is generally well tolerated. Before starting Entresto, make sure your healthcare professional knows your full health history and about any other medications you take. This will help them decide whether Entresto is right for you.

Common Entresto side effects include: 

• Mild hypotension (low blood pressure)

• Mild hyperkalemia (high potassium levels)

• Cough

• Dizziness

• Mild anemia (low red blood cell levels)

Entresto can also lead to more serious risks in rare cases, such as: 

• Severely low blood pressure

• Severely high potassium levels

• Kidney problems

• Angioedema (a severe allergic reaction that can cause swelling of the lips, throat, and deep tissues)

Entresto also has a boxed warning about the possibility of birth defects if you take it while pregnant. A boxed warning is the FDA’s strictest warning for medications.

Let’s take a closer look at five Entresto side effects and how to manage them.

1. Low blood pressure

Low blood pressure is the most commonly reported Entresto side effect. Sacubitiril and valsartan (the active ingredients in Entresto) work in different ways. But they can both lower your blood pressure, in addition to treating heart failure.

In most cases, the drop in blood pressure isn’t significant. But you may feel dizzy or lightheaded, especially when you first start taking Entresto. Move slowly when changing positions (such as sitting up or standing) to reduce the risk of falls until you know how Entresto affects you.

It’s less common, but a severe drop in blood pressure is also possible with Entresto. Certain factors can increase the risk of this side effect. These include being older, having low blood pressure prior to starting Entresto, and taking other medications that lower blood pressure.

Let your healthcare team know if you experience severe dizziness or lightheadedness while taking Entresto. They may recommend lowering your Entresto dosage or the dosage of other medications you take. But don’t make any changes without talking to your prescriber first.

2. High potassium levels

Entresto can raise your potassium levels. In most cases, this is a mild side effect that doesn’t cause any noticeable symptoms. But in rare cases, very high potassium levels are possible. This can lead to nausea, muscle weakness, or even an irregular heartbeat in severe cases.

The risk of high potassium levels while taking Entresto is greater if you:

• Are living with a health condition like diabetes, kidney damage, or hypoaldosteronism (low aldosterone levels)

• Consume a diet that's high in potassium

• Take other medications that can increase potassium levels, such as spironolactone (Aldactone) or potassium supplements

Your healthcare team will likely check your potassium levels with a blood test before you start Entresto and periodically while you’re taking it. If your potassium levels increase, your prescriber may lower your Entresto dosage. Or they may recommend switching to a different medication that’s less likely to cause this side effect.

3. Cough

A dry cough is another possible Entresto side effect related to valsartan. This side effect is more common with enalapril (Vasotec, Epaned) and other angiotensin-converting enzyme (ACE) inhibitors than with valsartan and other angiotensin II receptor blockers (ARBs). But it can still occur in some people taking Entresto.

Let your healthcare team know if you develop a persistent dry cough while you’re taking Entresto. They can help you figure out if this is due to Entresto or related to something else.

4. Kidney problems

Valsartan and other ARBs typically help protect the kidneys. But in rare cases, Entresto may cause worsening kidney function or even sudden kidney failure. 

Because kidney problems are possible with Entresto, it’s important to recognize the warning signs. Watch for symptoms such as:

• Producing little or no urine

• Swelling in your ankles or lower legs

• Feeling shorter of breath or more tired than usual

• Confusion

• Nausea

If you have existing kidney problems, you may be at higher risk for kidney-related side effects from Entresto. So be sure your healthcare team knows your complete medical history.

Taking certain medications with Entresto can also increase your risk of kidney damage. This includes nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil, Motrin).

Your prescriber should order lab tests (such as a creatinine blood test) to check your kidney function before and after you start taking Entresto. If your kidney function is lower than expected before treatment, they may start you at a lower Entresto dosage. If your kidney function worsens after starting this medication, you may need to lower your dosage or switch to another medication entirely.

5. Angioedema

Angioedema is a rare but serious side effect of Entresto. It can lead to severe swelling in the face, throat, and neck. In severe cases, it can also cause trouble breathing.

The risk of angioedema may be higher for Black people taking Entresto. There’s also an increased risk if you’ve experienced angioedema from any medication in the past.

If you experience swelling of your face, mouth, or throat or trouble breathing while taking Entresto, call 911 or go to the nearest ER.

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Written by:

Dena Westphalen, PharmD

Dena Westphalen, PharmD, serves as the director of scientific affairs for Cogent Biosciences, a biotechnology company developing treatments for genetically driven diseases. Westphalen’s career spans over 15 years with experience in research and hospital settings.

Edited by:

Stacia Woodcock, PharmD

Stacia Woodcock, PharmD, is a pharmacy editor for GoodRx. She earned her Doctor of Pharmacy degree from the University of Kentucky and is licensed in New York and Massachusetts.

Reviewed by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and served as a pharmacy editor for GoodRx.

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