Canada Pharmacy Depot

Managing Entresto Side Effects and Drug Interactions

Wednesday 3 April 2024
6 minute(s) read

Table of Contents

I. Entresto Side Effects

i. Low Blood Pressure (Hypotension)

ii. High Potassium Levels (Hyperkalemia)

iii. Kidney Issues

iv. Allergic Reaction

II. Entresto Drug Interactions

i. Angiotensin Converting Enzyme (ACE) Inhibitors

ii. Angiotensin II Receptor Blockers (ARBs)

iii. Diuretics

iv. Lithium

III. Conclusion

Entresto is prescribed for patients with heart failure with reduced ejection fraction to help manage symptoms and reduce hospitalization risk. [1] While this medication can provide significant benefits, it's important to be aware of potential side effects and drug interactions.

In this article, we'll discuss the potential side effects and drug interactions to watch out for with Entresto so you can have an informed discussion with your doctor.

Entresto Side Effects

For most people, Entresto is well-tolerated, and side effects are mild. But knowing the potential side effects is essential so you know what to watch out for.

The most common Entresto side effects include: 

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

These side effects are often mild, but you should immediately let your doctor know if you experience them.

Entresto can occasionally lead to more serious side effects that require medical attention. These include:

  • Dangerously low blood pressure
  • Severely high potassium
  • Kidney problems
  • Angioedema (swelling beneath the skin)
  • Birth defects if taken during pregnancy [1]

 Low Blood Pressure (Hypotension)

man taking his blood pressure

The most common side effect of Entresto is low blood pressure, also known as hypotension. This is expected given that one of Entresto's active ingredients, valsartan, is a blood pressure-lowering medication. Valsartan works by blocking angiotensin II receptors, which raise blood pressure. [1]

Certain factors can increase your risk of experiencing low blood pressure from Entresto.

  • Older age
  • Already having low blood pressure
  • Taking other blood pressure medications
  • Taking diuretics [1]

If you notice symptoms of low blood pressure, notify your doctor right away. They may recommend decreasing your dose of Entresto to help manage this side effect. [1]

High Potassium Levels (Hyperkalemia)

Taking Entresto can potentially lead to high blood potassium levels in some people. This side effect, known as hyperkalemia, tends to occur in those who already have conditions or factors that increase potassium levels, such as: [1]

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

To monitor this, your doctor will likely check your potassium levels before starting you on Entresto. They may also periodically check it while you are on the medication. [1]

Kidney Issues

While rare, kidney problems can occur while taking Entresto. [1] Some possible symptoms of kidney issues include:

  • Foamy urine
  • Change in urination frequency
  • Itchy or dry skin
  • Tiredness
  • Nausea
  • Loss of appetite
  • Unintentional weight loss [2]

Your doctor will check your kidney function with blood tests before you start Entresto and during treatment. If your kidney function is lower than normal, they may start you on a lower dose. If it worsens after starting Entresto, your dose may need to be lowered, or you may need to switch to a different medication. [1]

Allergic Reaction

For some people, Entresto can cause an allergic reaction known as angioedema. This severe reaction causes swelling in the deeper layers of the skin. [1] This can affect any part of the body, but the most common areas are:

  • Eyes
  • Lips
  • Genitals
  • Hands
  • Feet [3]

In clinical studies, angioedema occurred in 0.5% of participants taking Entresto, compared to 0.2% of those taking enalapril. So, while rare, Entresto does seem to increase the risk. [1]

If you experience any concerning symptoms while taking Entresto, contact your doctor right away. A severe reaction like swelling or trouble breathing is an emergency. You may need to stop Entresto and switch medications. Don't hesitate to call 911 if your allergic reaction seems life-threatening. [1]

Entresto Drug Interactions

prescription medication bottles

When taking Entresto, it's important to be aware of potential interactions with other medications. This heart failure drug can interact with several substances, which may impact how well it works or lead to increased side effects.

To avoid issues, have an open discussion with your doctor and pharmacist about everything you take before starting Entresto. Be sure to tell them about all prescription and over-the-counter medications, vitamins, herbs, and other supplements you use. Providing this complete picture helps them screen for possible interactions and recommend appropriate precautions.

Angiotensin Converting Enzyme (ACE) Inhibitors

Taking Entresto and an angiotensin converting enzyme (ACE) inhibitor at the same time can be risky. Using these two medications together raises your chance of angioedema, which is a severe allergic reaction. To avoid this problem, you need to separate the timing of Entresto and an ACE inhibitor by at least 36 hours. That allows enough time for the ACE inhibitor medication to leave your body. [1]

Some common ACE inhibitor drugs include:

  • Lisinopril (Zestril)
  • Quinapril (Accupril)
  • Ramipril (Altace)

If your doctor has prescribed an ACE inhibitor for you, be sure to discuss your Entresto treatment with them. They can advise you on properly timing the two medications and help you transition safely. With some planning and coordination with your doctor, you can take Entresto while avoiding negative interactions with ACE inhibitors. [1]

Angiotensin II Receptor Blockers (ARBs)

Entresto contains the active ingredient valsartan, which belongs to a class of medications called angiotensin II receptor blockers (ARBs). These drugs work by relaxing blood vessels, allowing blood to flow more easily and causing blood pressure to go down. [1] Other examples of ARBs include:

It's important to know that taking Entresto together with another ARB can increase levels of the drugs in your body, which raises your risk of side effects. For this reason, your doctor will likely have you stop taking any other ARB before starting treatment with Entresto. This helps ensure you don't end up with unsafe amounts of similar medications in your system. [1]


Diuretics, also called water pills, help your body eliminate extra fluid. However, some diuretics, known as potassium-sparing diuretics, also allow your body to hold onto potassium. Examples include:

  • Spironolactone (Aldactone)
  • Amiloride (Midamor)
  • Eplerenone (Inspra)

Entresto can also increase potassium levels. So, taking Entresto along with a potassium-sparing diuretic may push potassium levels too high. This side effect is called hyperkalemia. [1]

To prevent dangerous spikes in potassium, tell your doctor if you take any potassium-sparing diuretics. They can check your potassium levels throughout your Entresto treatment. [1]


If you are taking lithium, it is important to be aware that Entresto may increase lithium levels in your blood. Your body may not be able to eliminate lithium as quickly, causing the amount of lithium in your blood to rise. [1] This increase can potentially lead to lithium toxicity, which can cause:

  • Nausea
  • Vomiting
  • Tiredness
  • Muscle tremors [4]

To ensure your safety, your doctor will need to closely monitor your lithium levels through regular blood tests if you start taking Entresto. They may need to adjust your lithium dosage to keep levels in the right range based on your test results and symptoms. [1]


Entresto can be a helpful medication for people living with heart failure. However, as with any drug, it's critical to understand the risks and take the proper precautions. If you experience severe or worrisome side effects at any time, contact your healthcare provider right away.

To learn more about Entresto, visit our Entresto blog for more topics.

The content provided in this article is based on thorough research and in some cases, reviewed by a medical professional. Our goal for the information is to provide helpful, general health informational. It is not intended as a substitute for professional medical advice.