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

Entresto (sacubitril / valsartan) has been hailed as a “game changer” medication for treating heart failure since its approval in 2015. It’s the first medication of its kind: a combination of an angiotensin II receptor blocker (valsartan) and neprilysin inhibitor (sacubitril). 

Entresto is a first-choice medication for treating heart failure. But like nearly all medications, side effects are possible. Here, we’ll take a close look at five Entresto side effects.

Entresto side effects at a glance

Entresto is generally well tolerated. Still, possible Entresto side effects include: 

• Low blood pressure

• High potassium levels

• Cough

• Dizziness

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

• Severely low blood pressure

• Severely high potassium levels

• Kidney problems

• Swelling of deep tissues (angioedema)

This medication also has a boxed warning for birth defects if taken while pregnant. A boxed warning is the FDA’s strictest warning for medications.

Before starting Entresto, make sure your prescriber knows your full health history and other medications you take. This will help them decide whether Entresto is right for you.

1. Low blood pressure

Hypotension (low blood pressure) is the most commonly reported Entresto side effect. This side effect isn’t surprising, though. Valsartan, one of the medications in Entresto, is prescribed to lower blood pressure. It’s part of a group of medications called ARBs. These medications are prescribed for hypertension (high blood pressure), heart failure, and more.

Certain factors increase your risk of low blood pressure. This includes being of older age, having low blood pressure prior to Entresto treatment, and taking other medications that lower blood pressure.

EXPERT PICKS: WHAT TO READ NEXT

• Entresto basics: Learn how Entresto works and what type of heart failure it treats.

• Generic Entresto: Entresto isn’t available as a generic yet, but it may become available soon.

• Taking Entesto: The typical Entresto dosage is 1 tablet twice daily.

Symptoms of low blood pressure include feeling dizzy, lightheaded, or weak. Let your prescriber know if you experience any of these symptoms. They may recommend lowering your Entresto dosage or the dosage of other medications. But don’t make any changes without talking to your prescriber first.

2. High potassium levels

Hyperkalemia (high potassium levels) is another possible Entresto side effect. Potassium is a mineral you get from food. It plays an essential role in many bodily functions. For example, potassium helps your heart work efficiently and regulates blood pressure. 

Some people may be at an increased risk for hyperkalemia from Entresto. This includes people who:

• Have certain health conditions, such as diabetes, kidney damage, or low aldosterone (hypoaldosteronism)

• Consume a diet that's high in potassium

• Take medications that can increase potassium levels, including spironolactone (Aldactone) and potassium supplements

Symptoms of high potassium can include nausea, muscle weakness, and fatigue. But high potassium often doesn’t cause symptoms until it becomes very high (6 mEq/L or more). Very high potassium levels can cause arrhythmia (irregular heartbeat) and be life-threatening.

Your prescriber will likely monitor your potassium levels with a blood test before and during treatment with Entresto. If your potassium levels increase, your prescriber may lower your Entresto dosage. Or they may recommend another medication altogether.

3. Cough

Developing a dry cough is another possible Entresto side effect. This is due to the valsartan component. All ARBs, including valsartan, may cause a dry, hacking cough. 

But this is much less common with ARBs than it is with angiotensin-converting enzyme (ACE) inhibitors, another group of common blood pressure medications. For example, in the PARADIGM-HF study — the major study that led to Entresto’s FDA approval — cough was more common with the angiotensin-converting enzyme (ACE) inhibitor enalapril (Vasotec, Epaned) than it was with Entresto.

Let your cardiologist know if you develop a dry cough that doesn’t go away 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

Entresto may cause worsening kidney function or even sudden kidney failure. It’s rare, though. In fact, ARBs like valsartan help protect the kidneys in many cases. Still, kidney damage from Entresto is possible, so it’s a good idea to know what symptoms to watch out for. Examples include:

• Producing little or no urine

• Swelling in your ankles or lower legs 

• Tiredness

• Feeling short of breath

• 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 prescriber knows your complete medical history. And let them know what other medications you take as well. Taking certain medications with Entresto can increase your risk of kidney damage. This includes non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil, Motrin).

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

5. Swelling of deep tissues

Angioedema (swelling of deep tissues) is a rare but serious Entresto side effect. It typically presents in areas of the face, like the lips. It can also occur in the throat and neck. In severe cases, it can cause trouble breathing that’s life-threatening.

In the PARADIGM-HF study, Black people were more likely to experience angioedema from Entresto. You’re also at increased risk if you’ve experienced angioedema in the past. So Entresto isn’t recommended if you’ve ever had angioedema (even if it was from another medication, such as an ACE inhibitor).

If you experience swelling of your face, lips, tongue, or throat, or trouble breathing while taking Entresto, stop taking it and call 911 or go to the nearest ER. Most cases of angioedema resolve on their own, but if you develop trouble breathing you’ll need immediate medical care.

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Written by:

Alex Brewer, PharmD, MBA

Alex Brewer, PharmD, MBA, is a licensed pharmacist specializing in chronic disease and health and wellness. Upon completing his residency, he worked in the managed care field, conducting medication therapy management and adherence counseling sessions with Medicaid, Medicare, and private insurance patients, before transitioning to a career in medical writing.

Edited by:

Amy B. Gragnolati, PharmD, BCPS

Amy Gragnolati, PharmD, BCPS, is a pharmacy editor for GoodRx. Amy currently holds her pharmacist license in Georgia and California.

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