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Canadian Med Center

Managing Entresto Side Effects

Monday 8 April 2024
8 minute(s) read

Table of Contents

I. Common Entresto Side Effects

II. Serious Entresto Side Effects

i. Kidney Disease

ii. High Potassium Level

iii. Low Blood Pressure

iv. Angioedema

III. Entresto Drug Interactions

i. Entresto and Diuretics

ii. Entresto and Angiotensin Converting Enzyme (ACE) Inhibitors

iii. Entresto and Lithium

iv. Entresto and Angiotensin II Receptor Blockers (ARBs)

IV. Entresto Overdose

V. Conclusion

Entresto has emerged as a revolutionary medication for managing heart failure in both adults and children. While its effectiveness in improving heart health is well-documented, it is essential to be aware of potential side effects that may arise in some individuals. It's worth noting that not everyone will experience adverse reactions, and the effects can vary from person to person. [1]

This article will discuss symptoms associated with Entresto side effects, common Entresto drug interactions, and signs of an overdose.

Common Entresto Side Effects

Entresto is generally well-tolerated, but some people may experience mild side effects. In clinical trials, the most common side effects that occurred in more than 5% of participants taking Entresto were:

  • Cough (9%)
  • Low blood pressure (18%)
  • High potassium levels (12%)
  • Dizziness (6%) [1]

The good news is that these side effects are usually mild and temporary. However, you should always talk to your doctor or pharmacist if any symptoms are persistent or concerning. Do not stop taking Entresto unless instructed by your doctor. [1]

Serious Entresto Side Effects

In rare cases, Entresto may cause more serious side effects that require immediate medical attention. These potential side effects include:

  • Dangerously low blood pressure
  • Severely high potassium
  • Kidney disease
  • Angioedema [1]

Kidney Disease

picture of kidneys under a magnifying glass

While kidney problems are uncommon with Entresto, they can occur in some people. About 5% of clinical trial participants taking Entresto experienced kidney failure. [1]

Entresto works by inhibiting the renin-angiotensin-aldosterone system, which involves the kidneys. For this reason, decreases in kidney function may happen in susceptible individuals, including those with congestive heart failure. [1]

If you take Entresto, your doctor will monitor your serum creatinine closely to watch for any changes in kidney function. [1]

Some kidney failure symptoms to look out for include:

  • Foamy or bubbly urine
  • Needing to urinate more or less often
  • Dry, itchy skin
  • Feeling tired or weak
  • Nausea
  • Loss of appetite
  • Losing weight without trying [1]

Your doctor will check your kidney function with blood tests before starting Entresto and periodically during treatment.

  • If your kidney function is below normal before starting Entresto, your doctor may prescribe a lower starting dose for you.
  • If your kidney function declines after beginning Entresto, your doctor may lower your dosage or have you switch to a different medication entirely. [1]

High Potassium Level

When starting Entresto, it's important to be aware that it may lead to increased potassium levels in the blood, a condition called hyperkalemia. This side effect tends to happen more often in those with certain medical conditions that make them prone to high potassium. [1] These include:

  • Severe kidney impairment
  • Diabetes
  • Hypoaldosteronism
  • A diet high in potassium [1]

Before prescribing Entresto, your doctor will check your potassium levels. They’ll likely continue to monitor them periodically while you’re on the medication. This helps ensure your potassium doesn't get too high while you’re taking Entresto. [1]

Low Blood Pressure

One of Entresto's side effects is a drop in blood pressure. This is expected since Entresto contains valsartan, a medication that lowers blood pressure. [1]

While a blood pressure decrease is part of how Entresto helps heart failure, it can sometimes cause symptoms like

  • Dizziness
  • Fatigue
  • Fainting
  • Blurry vision
  • Confusion
  • Nausea [2]

Certain factors raise the risk of low blood pressure on Entresto:

  • Older age
  • Pre-existing low blood pressure
  • Use of other blood pressure medications
  • Taking diuretics [1]

If you fall into these categories, your doctor may correct sodium or fluid levels before starting Entresto. This can help stabilize your blood pressure in advance. If you still experience hypotension on Entresto, your doctor may adjust the dosage to alleviate side effects. [1]


Entresto can potentially cause a severe allergic reaction in some people, known as angioedema. [1] This reaction causes swelling beneath the skin that can occur anywhere on the body. The most affected areas include the eyes, lips, genitals, hands, and feet. [3]

While angioedema is rare, research shows it's more likely to occur with Entresto compared to other blood pressure medications. In clinical trials, about 0.5% of people taking Entresto experienced angioedema versus 0.2% of those taking the blood pressure medication enalapril. [1]

If you notice any concerning symptoms while taking Entresto, it's important to contact your doctor right away. Angioedema can rapidly progress and block the airway, so prompt medical attention is vital. [3] Your doctor may advise you to stop taking Entresto and switch to an alternative medication that's less likely to cause this reaction. [1]

Entresto Drug Interactions

When incorporating Entresto into your treatment plan, it's crucial to be mindful of its potential interactions with other medications. Entresto can interact with medications in the following drug classes:

  • Diuretics
  • Angiotensin Converting Enzyme (ACE) inhibitors
  • Lithium
  • Angiotensin II Receptor Blockers (ARBs) [1]

Entresto and Diuretics

Diuretics are medications that help your kidneys remove excess fluid from your body. Some diuretics, known as potassium-sparing diuretics, have the added benefit of preventing your body from losing too much potassium. However, for some people, potassium-sparing diuretics can cause potassium levels to become too high when taken along with other drugs like Entresto. [1]

Entresto can increase potassium levels in the body. Taking Entresto and a potassium-sparing diuretic together could potentially push your potassium up to dangerous levels, a condition called hyperkalemia. [1] Hyperkalemia can cause symptoms such as

  • Muscle weakness
  • Numbness
  • Tingling
  • Nausea
  • Chest pain
  • Shortness of breath
  • Heart palpitations [4]

To avoid the risks associated with high potassium, be sure to tell your doctor if you take any potassium-sparing diuretics. Your doctor can monitor your potassium levels closely while you are on Entresto to catch any spikes early on. [1]

Entresto and Angiotensin Converting Enzyme (ACE) Inhibitors

Taking Entresto and an ACE inhibitor at the same time is not recommended. Using these two medications together raises your chance of experiencing unwanted side effects like:

  • Angioedema
  • Low blood pressure
  • Acute kidney injury
  • Increased potassium levels [1]

To prevent any potential issues, it is crucial to separate the timing of taking Entresto and an ACE inhibitor by at least 36 hours. This time gap allows sufficient time for the ACE inhibitor medication to fully metabolize and exit your body. [1]

Entresto and Lithium

If you are currently using lithium, it is crucial to be aware of the potential interaction between lithium and Entresto.

Entresto has the potential to increase the levels of lithium in your blood, which means that your body may not be able to eliminate lithium as efficiently as it normally would. This can result in an accumulation of lithium in your bloodstream, leading to a condition known as lithium toxicity. [1]

Symptoms of lithium toxicity include:

  • Fatigue
  • Nausea
  • Vomiting
  • Muscle tremors [5]

If you’re taking lithium along with Entresto, your doctor will closely monitor your lithium levels. Based on the test results and any symptoms you're experiencing, your doctor may adjust your lithium dosage. [1]

Entresto and Angiotensin II Receptor Blockers (ARBs)

Entresto contains valsartan, which belongs to a class of drugs called angiotensin II receptor blockers (ARBs). These medications work by relaxing blood vessels to lower blood pressure. [1]

If you take Entresto along with another ARB medication, it can lead to unsafe levels of similar drugs building up in your body. This puts you at risk of side effects like

  • Dizziness
  • Cough
  • Low blood pressure
  • High potassium levels [1]

To avoid these issues, your doctor will have you stop taking any other ARB before beginning treatment with Entresto. This ensures your body only has a safe amount of this type of medication at one time. [1]

Entresto Overdose

prescription medications spilling out of medication bottle

There is limited data available on Entresto overdose, as clinical studies have only evaluated the effects of high doses in healthy volunteers. However, these studies give us some idea of what to expect with an overdose.

In one study, volunteers took a single high dose of 583 mg of sacubitril and 617 mg of valsartan. This massive single dose was well tolerated by the healthy participants. [1]

In another study, volunteers took high daily doses of 437 mg of sacubitril and 463 mg of valsartan for 14 days. Again, these large, repeated doses did not cause significant issues for the healthy volunteers. [1]

It is important to note that, given Entresto's ability to lower blood pressure, the most likely effect of an overdose would be a drop in blood pressure. If you suspect that you or someone you know has taken an overdose of Entresto, it is crucial to seek emergency medical care. [1]


Entresto is a valuable medication for managing heart failure, but like all medications, it comes with potential side effects and risks.

By understanding the side effects of Entresto, being aware of potential drug interactions, and avoiding overdose, patients can effectively manage their treatment and optimize their outcomes.

To stay informed about Entresto, visit our Entresto blog for more information.

The content in this article is intended for informational purposes only. This website does not provide medical advice. In all circumstances, you should always seek the advice of your physician and/or other qualified health professionals(s) for drug, medical condition, or treatment advice. The content provided on this website is not a substitute for professional medical advice, diagnosis, or treatment.