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Entresto side effects and how to avoid them

Side effects are possible, but there are ways to manage and avoid them
Leandra Beabout
By | Updated on Mar. 10, 2026 Medically reviewed by Anne Jacobson, MD, MPH & Samantha Marr, DNP, APN, AGPCNP-BC, CCRN
Rx pad with prescription bottle: Entresto side effects

Key takeaways

  • Entresto, a heart failure medication, can cause side effects like low blood pressure, high potassium, cough, and dizziness.

  • Serious Entresto side effects include dangerous blood pressure drops, very high potassium levels, and life-threatening allergic reactions.

  • Patients can reduce the risk of side effects by informing their providers of any health conditions or medication changes, taking their daily doses as prescribed, and avoiding certain foods and drugs.

In this article:

Entresto is a brand-name prescription medication used to reduce the risk of hospitalization and death in people with chronic heart failure. It contains a combination of sacubitril and valsartan, two drugs that relax blood vessels and lower blood pressure. This combination makes Entresto a first-of-its-kind medication in a new class of drugs called angiotensin receptor neprilysin inhibitors (ARNIs). 

Like most medications, Entresto can cause side effects. It’s important to understand the potential side effects and risks of this drug before starting it.

Common side effects of Entresto

The most common side effects of Entresto are low blood pressure (hypotension) and high potassium (hyperkalemia). In clinical trials, 18% of Entresto users developed low blood pressure, and 12% developed high potassium levels.

Entresto side effects that occurred in 6% or more of clinical trial participants include:

What are the worst side effects of Entresto?

Serious side effects of Entresto include:

Serious allergic reactions to Entresto are not common, but it’s still important to monitor for signs of hypersensitivity. Seek medical attention for symptoms of an allergic reaction, including itchiness, hives, and a severe allergic reaction called anaphylaxis, which causes rapid or irregular heartbeat, trouble breathing, and loss of consciousness. 

Entresto side effects in elderly patients

Heart problems are more common in older adults, and research indicates that more than 8% of adults ages 75 and older have heart failure. This means many Entresto users are older adults. Fortunately, clinical trials found no differences in the safety and effectiveness of Entresto in older adults versus younger adults. 

That said, older patients are more likely to have other medical conditions and be on other prescription drugs that could interact with Entresto. Possible side effects like low blood pressure and kidney problems can also be more dangerous for older adults. For instance, low blood pressure can cause dizziness, lightheadedness, or fainting. Additionally, blood pressure drops are linked to an increased risk of falls. Acute kidney failure is also associated with worse outcomes in older adults, including death.

Does Entresto cause weight gain?

No, research does not indicate that Entresto causes weight gain. However, acute kidney failure, an Entresto side effect, can cause rapid weight gain from fluid retention. Seek medical advice for sudden or significant weight gain after starting Entresto.

How soon do Entresto side effects start?

Entresto works within hours of administration, so side effects may develop within the first few days of use. The first noticeable side effect of Entresto is low blood pressure, which is marked by lightheadedness, unusual fatigue, or dizziness, according to Chrissie Ott, MD, a healthcare advocacy consultant in Portland, Oregon, who is double board-certified in internal medicine and pediatrics. “This usually settles on its own, but it is a good reason to monitor your blood pressure at home and report to your provider if it is worrisome.”

Do Entresto side effects go away?

Side effects generally settle over time, but Dr. Ott stresses the importance of regularly monitoring blood pressure and potassium levels. Since Entresto can, in rare cases, negatively impact kidney function, it’s also important for patients with preexisting kidney conditions to discuss the risks versus benefits of Entresto with their healthcare provider.

Research shows that Entresto can offer benefits even at lower doses. Individuals concerned about long-term side effects should consult their healthcare provider about the lowest effective dose. For people whose bodies never fully tolerate the medication, discontinuation may be necessary. 

Entresto interactions

Certain drugs and foods should not be taken with Entresto due to the risk of an adverse interaction. 

Foods to limit or avoid on Entresto include:

Drug types that interact with Entresto include:

  • Angiotensin converting enzyme (ACE) inhibitors
  • Angiotensin II receptor blockers (ARBs)
  • Aliskiren
  • Potassium-sparing diuretics
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) 
  • Lithium

ACE inhibitors

ACE inhibitors like lisinopril, quinapril, and Lotensin (benazepril) are commonly prescribed to treat high blood pressure. Taking one of these medications with Entresto can cause a dangerous drop in blood pressure. 

ARBs

Entresto contains valsartan, an ARB. Taking Entresto in addition to another ARB like losartan (generic Cozaar), Diovan (valsartan), candesartan, and Avapro (irbesartan) at the same time is essentially like double-dosing the ARB. This dramatically increases the risk of severe side effects like high potassium, very low blood pressure, and acute kidney damage. 

Aliskiren

Aliskiren is the generic version of the brand-name drug Tekturna. Like ACE inhibitors, aliskiren is primarily used to lower blood pressure. Combining it with Entresto can cause dangerously low blood pressure, which may trigger extreme lightheadedness or loss of consciousness.

Potassium-sparing diuretics

Potassium-sparing diuretics, such as spironolactone, triamterene, and amiloride, are often prescribed for high blood pressure. Diuretics, also called water pills, flush out the kidneys by increasing urine output. As the name implies, potassium-sparing diuretics “spare” potassium from being excreted. Combining these with Entresto, which can cause high blood potassium levels, only increases the chance of hyperkalemia.

NSAIDs

NSAIDs like ibuprofen offer over-the-counter pain relief and fever reduction. They can also lead to the development of kidney problems, which is already a risk of taking Entresto. NSAIDS should be used with caution while taking Entresto.

Lithium

Entresto increases lithium in the blood. Given that, taking lithium while on Entresto can pose a risk of lithium toxicity. If these two medications are accidentally combined, tell your healthcare provider and monitor for signs of toxicity, such as tremors or loss of consciousness.

Who should not take Entresto?

People with the following conditions should also avoid taking Entresto:

  • Pregnancy
  • Severe hepatic impairment (liver disease)
  • Diabetic high blood pressure that’s being treated with Tekturna (aliskiren) 
  • History of angioedema after taking an ACE inhibitor or ARB
  • History of allergic reaction to any of Entresto’s ingredients

Entresto has a boxed warning (black box warning) against use during pregnancy. The label states that Entresto can cause injury or death to a developing fetus. Tell your provider immediately if you are pregnant or planning to become pregnant while taking Entresto. It’s also essential to consult a healthcare provider before breastfeeding while taking Entresto.

How to avoid Entresto side effects

Some Entresto side effects can be managed or avoided with a few simple strategies:

  1. Take Entresto at the same time each day. “Taking Entresto at the same time each day is more important than whether or not you take it with food,” Dr. Ott says. “Entresto is a twice-daily medication, so scheduling a morning and evening time for dosing about twelve hours apart is ideal.” Consistent timing ensures that the medication stays at a steady level in the body from day to day.
  2. Start with a low dose. Entresto dosage starts at 24/26 mg tablets taken twice daily. Ask your provider about staying at this low dose until your body gets used to the medication. After that, most patients advance to 97/103 mg tablets taken twice daily.
  3. Communicate any medication and supplement changes to your provider. Your prescribing healthcare provider needs to review a complete medication list, including over-the-counter medicines and supplements, before you start Entresto. Once treatment has started, don’t forget to inform your provider about changes to avoid dangerous drug interactions.
  4. Report concerns to your provider. Entresto is typically taken long-term. Still, it’s important to report new, persistent, or worsening side effects. “If you have severe or persistent dizziness, your dose may need to be adjusted, “ Dr. Ott says.
  5. Monitor your diet. Remember, Entresto increases the risk of high potassium. It’s very important to avoid potassium supplements and salt supplements while on Entresto, according to Juliana Vocca, RD, a registered dietitian at Prime Women Nutrition in Moorestown, New Jersey.
  6. Keep your follow-up appointments. Dr. Ott says blood tests should be done within one to two weeks of starting Entresto to make sure potassium levels are still in the safe zone. 
  7. Focus on a heart-healthy lifestyle. People on Entresto already have heart problems. “[Follow] a heart-healthy diet by eating fruits, vegetables, and whole grains, low-fat dairy, and limiting foods high in saturated fat and sodium,” Vocca says. She also emphasizes the importance of regular exercise.

How to save on Entresto

Entresto can be expensive without insurance or discounts. Fortunately, there are ways to save on brand-name Entresto and its generic form, sacubitril-valsartan.

One way to save is by using SingleCare coupons or a SingleCare prescription discount card. For instance, the average retail price of Entresto is $970 for 60, 24-26 mg tablets. With a SingleCare coupon, you could pay $48 for 60, 24–26 mg tablets of generic sacubitril-valsartan, depending on your choice of pharmacy.

RELATED: How does SingleCare work?

The SingleCare prices in this article are the most accurate at the time of publishing in ZIP code 23666 as of Feb. 13, 2026. Prices vary by pharmacy. Visit our Entresto coupon page for updated Entresto prices near you.

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