Key takeaways:
Entresto (sacubitril / valsartan) is used to treat heart failure. It combines an older heart medication with a newer type of heart medication.
Entresto works by reducing stress on the heart and strengthening its pumping function.
Entresto can improve symptoms and quality of life for people with certain types of chronic (long-lasting) heart failure. In some cases, it can also decrease the risk of being hospitalized or dying from heart failure.
There are many ways to save on Entresto, which is currently only available as a brand-name medication. If you’re eligible, a manufacturer savings card can help you get Entresto for as little as $10 per prescription. A patient assistance program is also available.
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Entresto (sacubitril / valsartan) is the first and only medication in its class. It’s FDA approved for two types of heart failure:
Heart failure with reduced ejection fraction (HFrEF): This condition occurs when the left side of the heart doesn't pump out enough blood with each heartbeat. With HFrEF, a person’s ejection fraction is less than or equal to 40%. This means that no more than 40% of the total amount of blood in the heart is pumped out with each contraction.
Heart failure with preserved ejection fraction (HFpEF): This is when the left side of the heart can pump normally, but it doesn’t fill properly during the relaxation phase of each heartbeat. With HFpEF, a person’s ejection fraction is over 40%.
Here, we cover some key facts about this medication, including what Entresto is, how it works, and what side effects to watch out for when taking it.
What is Entresto?
Entresto combines two medications:
Valsartan (Diovan): Valsartan is an angiotensin II receptor blocker (ARB) that’s commonly used to treat heart conditions and high blood pressure.
Sacubitril: Sacubitril is a neprilysin inhibitor and the ingredient that makes Entresto unique compared to other ARBs.
Entresto comes as an oral tablet in three doses: 24 mg / 26 mg, 49 mg / 51 mg, and 97 mg / 103 mg of sacubitril / valsartan. Entresto tablets can also be made into an oral liquid by your pharmacist if you can’t swallow tablets.
Alternatively, Entresto Sprinkle comes as a capsule that contains oral pellets. The capsule is meant to be opened. The oral pellets can then be sprinkled on a teaspoon or two of soft food for immediate consumption. Entresto Sprinkle comes in two doses: 6mg / 6mg and 15mg / 16mg of sacubitril / valsartan.
What is Entresto used for?
Entresto is used to treat chronic heart failure and improve symptoms of heart failure in adults. Symptoms of heart failure include shortness of breath, fatigue, and swelling.
Originally, Entresto was approved for adults with HFrEF only. Research has shown that Entresto can improve HFrEF and prevent hospitalization or death from this type of heart failure.
In 2021, the FDA expanded its approval of Entresto to include adults with HFpEF. However, Entresto isn’t considered as effective at treating HFpEF as it is at treating HFrEF. For example, a major study on Entresto called the PARAGON-HF trial found that Entresto didn’t reduce the risk of hospitalization or death from HFpEF more than valsartan alone.
What this tells us is that Entresto is most effective for people with HFrEF. For people with HFpEF, Entresto may be helpful when added to a sodium-glucose cotransporter 2 (SGLT2) inhibitor. SGLT2 inhibitors are considered the mainstay of treatment for HFpEF.
What drug class is Entresto in?
Entresto is an angiotensin receptor-neprilysin inhibitor, or ARNI for short. As mentioned, it combines an ARB with a neprilysin inhibitor. Entresto is the only medication in this drug class.
How does Entresto work?
Entresto works by taking stress off of the heart. It can also help improve the heart’s pumping function. Both of these actions can improve the symptoms of heart failure, including breathlessness, low energy levels, and swelling.
More specifically, the valsartan in Entresto works by blocking a hormone called angiotensin II. Typically, angiotensin II causes blood vessels to narrow. By blocking this hormone, valsartan expands blood vessels and decreases blood pressure. This makes it easier for the heart to pump blood to the rest of the body and improves your ejection fraction.
The sacubitril in Entresto blocks the protein neprilysin. Blocking neprilysin increases certain substances in the body that benefit the heart, blood vessels, and kidneys. This can improve blood flow in people with heart failure. Sacubitril also helps the body get rid of extra fluid, reducing fluid retention — a common problem in people with chronic heart failure.
What are the most common side effects of Entresto?
Entresto’s side effects are similar to those of ARBs and a group of similar medications called angiotensin-converting enzyme (ACE) inhibitors. Examples of common Entresto side effects include:
Hypotension (low blood pressure)
Dizziness and lightheadedness
High potassium levels
Cough
More rarely, kidney problems, extremely high potassium levels, and severely low blood pressure can occur. Angioedema, a severe reaction that can cause throat swelling and trouble breathing, is also a rare but serious side effect of Entresto.
Before and during treatment with Entresto, your prescriber will ask you to complete blood tests to measure your potassium and kidney function. They will also monitor your blood pressure closely while you’re taking the medication.
What medications shouldn’t be taken with Entresto?
Entresto can be safely taken alongside many medications, but it does have possible drug interactions. For example, Entresto can interact with:
Medications that lower blood pressure, such as ACE inhibitors and ARBs
Medications that increase potassium, such as potassium supplements and spironolactone (Aldactone)
Medications that increase the risk of kidney problems, such as the nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen (Advil, Motrin) and aspirin
Lithium (Lithobid)
Some of these potential interactions may need to be avoided completely. In other cases, your prescriber may just recommend watching for signs of an interaction.
For more information on what medications to avoid with Entresto, head to this GoodRx Health article on possible interactions.
What is the Entresto ‘washout period’?
Because Entresto works similarly to ACE inhibitors and ARBs, a “washout period” of 36 hours is required between taking one of these medications and Entresto. This means you will need to stop taking any ACE inhibitor or ARB you’ve been prescribed for 36 hours prior to starting Entresto.
The washout period helps to lower your chances of side effects from taking too much of the same type of medication.
Who shouldn’t take Entresto?
Certain people may need to avoid Entresto, including people who:
Have low systolic blood pressure (less than 100 mmHg)
Have a history of angioedema
Have an allergy to Entresto
Have severe liver disease
Are pregnant or breastfeeding
Take an ACE inhibitor or ARB
Have diabetes and take aliskiren (Tekturna)
Can't reliably afford Entresto, which may lead to inconsistency in treatment
There may be other reasons to avoid Entresto. So talk with your healthcare professional about which heart failure medications are best for you.
How to save on Entresto
Entresto is currently only available as a brand-name medication. The FDA approved a generic version of the medication in May 2024, but it won’t be available until Entresto’s first patent expires in July 2025 (at the earliest). In the meantime, there are a few ways to save on brand-name Entresto:
Receive a free month of Entresto. Entresto’s manufacturer offers a one-time, free 30-day supply of Entresto. Anyone can redeem this free trial, regardless of whether they have insurance.
Use a manufacturer savings card. If you have commercial insurance, you may be eligible to receive Entresto for as little as $10 per prescription with a copay savings card from the manufacturer.
Enroll in a patient assistance program. If you’re uninsured or underinsured, you may qualify for Entresto’s patient assistance program. You could receive Entresto free of cost if you’re eligible.
Frequently asked questions
Tylenol (acetaminophen) is one over-the-counter pain reliever that’s considered safe to take with Entresto.
NSAIDs like ibuprofen and naproxen (Aleve, Naprosyn) can increase your risk of kidney problems when taken with Entresto. Still, your prescriber may think short-term NSAID use is safe for you, depending on your kidney health. So talk to them about what the best pain reliever for you is.
If you suddenly stop taking Entresto, you may experience worsening symptoms of heart failure, like fatigue and shortness of breath. You could also be at higher risk for complications from heart failure and hospitalization.
If you’re experiencing bothersome Entresto side effects, let your prescriber know. They may recommend a different heart failure medication. But you shouldn’t make changes to your medication regimen or suddenly stop taking Entresto on your own. One exception would be if you experience angioedema, or swelling of the face, throat, and neck. This can be a life-threatening reaction and requires immediate medical care.
Several heart failure medications are known to improve life expectancy for people with the condition, including Entresto. They do this by reducing the risk of hospitalization and death from heart failure.
One study showed that Entresto extended life expectancy for people with heart failure by an average of 1 to 2 years. This was in a study comparing enalapril (Vasotec) to Entresto. Enalapril is a type of ACE inhibitor and a popular treatment option for many people with heart failure.
No, Entresto is currently available only as a brand-name medication. The FDA approved the first generic versions of Entresto in 2024. But these generics can’t be marketed because the patents on brand-name Entresto haven’t expired yet. Generic versions of Entresto could be available as early as July 2025 based on projected patent expirations.
Tylenol (acetaminophen) is one over-the-counter pain reliever that’s considered safe to take with Entresto.
NSAIDs like ibuprofen and naproxen (Aleve, Naprosyn) can increase your risk of kidney problems when taken with Entresto. Still, your prescriber may think short-term NSAID use is safe for you, depending on your kidney health. So talk to them about what the best pain reliever for you is.
If you suddenly stop taking Entresto, you may experience worsening symptoms of heart failure, like fatigue and shortness of breath. You could also be at higher risk for complications from heart failure and hospitalization.
If you’re experiencing bothersome Entresto side effects, let your prescriber know. They may recommend a different heart failure medication. But you shouldn’t make changes to your medication regimen or suddenly stop taking Entresto on your own. One exception would be if you experience angioedema, or swelling of the face, throat, and neck. This can be a life-threatening reaction and requires immediate medical care.
Several heart failure medications are known to improve life expectancy for people with the condition, including Entresto. They do this by reducing the risk of hospitalization and death from heart failure.
One study showed that Entresto extended life expectancy for people with heart failure by an average of 1 to 2 years. This was in a study comparing enalapril (Vasotec) to Entresto. Enalapril is a type of ACE inhibitor and a popular treatment option for many people with heart failure.
No, Entresto is currently available only as a brand-name medication. The FDA approved the first generic versions of Entresto in 2024. But these generics can’t be marketed because the patents on brand-name Entresto haven’t expired yet. Generic versions of Entresto could be available as early as July 2025 based on projected patent expirations.
The bottom line
Entresto is a prescription-only heart failure medication that combines valsartan, an angiotensin II receptor blocker (ARB), and sacubitril, a neprilysin inhibitor. It’s the first and only angiotensin receptor neprilysin inhibitor (ARNI). And it’s been shown to decrease the risk of hospitalization and death in people with certain types of heart failure. For many people with heart failure, Entresto is recommended as an alternative to ARBs and angiotensin-converting enzyme inhibitor (ACE) inhibitors.
Always follow your prescriber’s instructions for taking Entresto. There may be specific directions for how to start or stop the medication.
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References
American Heart Association. (2023). Ejection fraction heart failure measurement.
Claggett, B., et al. (2015). Estimating the long-term treatment benefits of sacubitril–valsartan. The New England Journal of Medicine.
Hubers, S. A., et al. (2016). Combined angiotensin receptor antagonism and neprilysin inhibition. Circulation.
Januzzi, J. L., Jr., et al. (2019). Association of change in N-terminal pro-B-type natriuretic peptide following initiation of sacubitril-valsartan treatment with cardiac structure and function in patients with heart failure with reduced ejection fraction. JAMA.
Kittleson, M. M., et al. (2023). 2023 ACC expert consensus decision pathway on management of heart failure with preserved ejection fraction: A report of the American College of Cardiology Solution Set Oversight Committee. Journal of the American College of Cardiology.
McMurray, J. J. V., et al. (2014). Angiotensin-neprilysin inhibition versus enalapril in heart failure. The New England Journal of Medicine.
Novartis International AG. (2021). Novartis Entresto granted expanded indication in chronic heart failure by FDA. GlobeNewswire.
Solomon, S. D., et al. (2019). Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction. The New England Journal of Medicine.
Wang, T. D., et al. (2017). Effects of sacubitril/valsartan (LCZ696) on natriuresis, diuresis, blood pressures, and NT-proBNP in salt-sensitive hypertension. Hypertension.
