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Entresto washout period: Considerations when switching medications

Entresto cannot be used with ACE inhibitors
Karen Berger medical writer and reviewer headshot
By | Jul. 31, 2024
A clock and two pills: Entresto washout period

Key takeaways

  • A 36-hour washout period between stopping an ACE inhibitor and starting Entresto is crucial to prevent the risk of life-threatening angioedema. This also applies to stopping Entresto and starting an ACE inhibitor—at least 36 hours must elapse.

  • Entresto should not be combined with ACE inhibitors, ARBs, or certain other medications due to the increased risk of severe side effects, including angioedema and kidney problems.

  • Always inform your healthcare provider of all medications you are taking and any medical conditions you have to ensure Entresto is prescribed safely.

In this article:

Entresto (sacubitril/valsartan) is a medicine that is classified as an angiotensin receptor neprilysin inhibitor (ARNI). Sacubitril is a neprilysin inhibitor, and valsartan is an angiotensin II receptor blocker. Entresto is made by the pharmaceutical company Novartis and was approved by the Food and Drug Administration (FDA) in 2015. It can be used along with other medicines to lower the risk of death and hospitalization in adults who have certain types of chronic heart failure and is especially helpful for those with reduced ejection fraction. Entresto can also be used to treat certain types of heart failure in pediatric patients ages 1 year or older. 

You may have heard of an Entresto washout period and wonder what it means. Entresto is contraindicated (cannot be used) with any medicine in the angiotensin-converting enzyme (ACE or ACEI) inhibitor class of drugs, such as lisinopril or enalapril. What’s more, a “washout period” must occur, meaning your healthcare provider may require that you wait a specific amount of time before switching from another drug to Entresto, or vice versa. Continue reading to learn more about the washout period associated with Entresto.

What is the Entresto washout period?

A washout period is the amount of time it takes for a drug to be eliminated from the body or to become ineffective. In regard to Entresto, the Entresto period refers to a period of time between two different treatments. That’s because Entresto cannot be used in combination with an ACE inhibitor drug because of the risk of angioedema, a type of reaction (we’ll talk more about this below). After taking the last dose of an ACE inhibitor, the patient must have a 36-hour washout period before starting Entresto. The opposite also applies—at least 36 hours must elapse if switching from Entresto to an ACE inhibitor.

Some examples of ACE inhibitors include:

This washout period also applies to combination medications that contain an ACE inhibitor, such as lisinopril/hydrochlorothiazide. 

Entresto washout period: Why does it matter?

Angioedema is a reaction that causes swelling beneath the skin. ACE inhibitor drugs are the most common group of drugs that cause angioedema. Angioedema symptoms caused by ACE inhibitors generally occur over several hours and may include swelling of the face, lips, tongue, or upper airway. This type of reaction is a medical emergency. It can be life-threatening if swelling blocks the airways and does not allow air to move in and out of the lungs. About one-third of people with angioedema caused by an ACE inhibitor will require a stay in an intensive care unit, and about 10% will need to be intubated. 

People who take an ACE inhibitor in combination with Entresto (specifically due to the ingredient sacubitril) are at higher risk of angioedema. This is why Entresto and an ACE inhibitor should never be used together. 

The 2022 Guideline for the Management of Heart Failure notes that, for patients who are switched from an ACE inhibitor to an ARNI, at least 36 hours must elapse between the last dose of an ACE inhibitor and the first dose of Entresto. As of 2024, Entresto is the only ARNI on the market), The reverse is also true: A patient who is switching from Entresto to an ACE inhibitor should also wait at least 36 hours between the last dose of Entresto and the first dose of an ACE inhibitor. 

Also, Entresto should not be used in combination with an angiotensin receptor blocker (ARB). However, the American College of Cardiology recommends stopping the ARB and then taking the first dose of Entresto at the time of the next dose, generally in 12 or 24 hours. 

Entresto contraindications

Entresto is not safe for everyone. The following patients should not take Entresto:

  • People who are allergic to sacubitril, valsartan, or any ingredient in Entresto
  • People with a history of angioedema from previous treatment with an ACE inhibitor or an ARB, such as Cozaar (losartan) and Diovan (valsartan) 
  • People who take an ACE inhibitor (due to increased risk of angioedema)
  • People who take an ARB (due to increased risk of low blood pressure, renal impairment, and high serum potassium levels)
  • People who take a medicine called aliskiren and have diabetes
  • People who take aliskiren and have problems with renal function (estimated glomerular filtration rate (eGFR) less than 60)
  • People with severe liver problems
  • Individuals who are pregnant or breastfeeding

Before you take Entresto, tell your healthcare provider about all of your medical conditions. In addition to the above contraindications, Entresto must be used with caution in people with certain other health conditions, such as low blood pressure.

Other drug interactions associated with Entresto

In addition to ACE inhibitors, ARBs, and aliskiren, other Entresto drug interactions include:

  • Potassium-sparing diuretics, potassium supplements, or salt substitutes that contain potassium: Concomitant use of any of these with Entresto can lead to hyperkalemia (high potassium levels).
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) combined with Entresto can lead to kidney problems or kidney failure, especially in older adults or people who take diuretics (water pills) or have kidney problems. Examples of NSAIDs include ibuprofen and naproxen. 
  • Lithium combined with Entresto can cause high lithium levels, which can lead to more severe adverse effects and lithium toxicity. People who take lithium with Entresto must have their blood work closely monitored. 

Before you take Entresto, tell your healthcare provider about all the medications you take, including prescription drugs, over-the-counter medicines, and any natural products like vitamins or supplements. This will help your provider decide whether Entresto can be safely prescribed. If you are not sure whether you are taking an ACE inhibitor or ARB, check with your healthcare provider or pharmacist.