Key takeaways:
Entresto (sacubitril / valsartan) is a medication that treats heart failure. It has a number of interactions to know about.
Key Entresto interactions include lisinopril (Zestril, Qbrelis), losartan (Cozaar), and ibuprofen (Advil, Motrin). It also interacts with aliskiren (Tekturna), spironolactone (Aldactone), and potassium supplements.
Some Entresto interactions should be avoided due to the risk of severe side effects. With other interactions, your healthcare team may monitor your potassium levels or kidney function more closely.
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When Entresto was FDA approved in 2015, it changed the way heart failure was treated. It’s a unique combination of two medications: sacubitril and valsartan. Now, Entresto is a first-choice medication for treating heart failure.
Like all medications, Entresto has possible side effects and drug interactions. Here, we’ll cover six of the most important Entresto interactions you should know about.
Entreso interactions
The following medications and supplements interact with Entresto:
Angiotensin-converting enzyme (ACE) inhibitors, such as lisinopril (Zestril, Qbrelis)
Angiotensin II receptor blockers (ARBs), such as losartan (Cozaar)
Aliskiren (Tekturna)
Medications that raise potassium levels, such as spironolactone (Aldactone)
Potassium supplements
Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil, Motrin)
Lithium (Lithobid)
This isn’t a complete list. So be sure to tell your healthcare team about all the medications and supplements you take. Below, we’ll dig deeper into what you should know about six Entresto interactions.
1. ACE Inhibitors such as lisinopril
You shouldn’t take Entresto with ACE inhibitors. Examples of ACE inhibitors include:
Enalapril (Vasotec)
Benazepril (Lotensin)
Quinapril
Ramipril
Captopril
Fosinopril
The reason for this interaction is the sacubitril ingredient in Entresto. Taking sacubitril and an ACE inhibitor increases your risk of angioedema. This is a swelling of the deep tissues in the body. This commonly includes the tongue, throat, lips. It can also happen in the face and neck. If the swelling is severe, it can cause your airways to close up and make it difficult to breathe. If you have trouble breathing, it requires emergency medical treatment. This is why it’s best to avoid taking Entresto with ACE inhibitors.
Good to know: ACE inhibitors are commonly used to treat many conditions. This includes heart failure and high blood pressure. If you take an ACE inhibitor and your prescriber recommends Entresto for heart failure, you’ll have to stop your ACE inhibitor. You should wait at least 36 hours (1.5 days) after your last dose of the ACE inhibitor to start Entresto. Follow your prescriber’s instructions for making this switch.
2. ARBs such as losartan
Entresto contains an ARB called valsartan. So you shouldn’t take an additional ARB if you’re taking Entresto. Doing so raises your risk of side effects, including low blood pressure, kidney problems, and high potassium levels (hyperkalemia).
Examples of ARBs include:
Olmesartan (Benicar)
Telmisartan (Micardis)
Valsartan (Diovan)
Irbesartan (Avapro)
Candesartan (Atacand)
Azilsartan (Edarbi)
If you’ve been taking an ARB, your prescriber should have you stop it before starting Entresto. But don’t make the switch without specific instructions from your prescriber about how to do so.
3. Aliskiren
Most people shouldn’t take Entresto with the blood pressure medication aliskiren. This is due to the valsartan ingredient in Entresto. Taking valsartan (or any ARB) and aliskiren together can raise the risk for kidney problems, low blood pressure, and high potassium levels.
People with diabetes or kidney problems have an even greater risk for these complications. That’s why taking Entresto and aliskiren together is contraindicated for people with these conditions. A contraindication is a situation when you shouldn’t take a medication because the risks outweigh the benefits for most people.
Entresto side effects: Many Entresto (sacubitril / valsartan) interactions raise the risk for side effects, such as low blood pressure and high potassium levels.
Is there a generic for Entresto? Pharmacists answer this and other Entresto frequently asked questions.
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If you take aliskiren, let your prescriber know before starting Entresto. They’ll likely have you stop taking aliskiren. But if they do recommend taking both, your prescriber should routinely check your kidney function and potassium levels. It’s important to go for all of your blood tests on time.
4. Medications that increase potassium
Entresto can increase the amount of potassium in your blood. So it can interact with other medications and substances that have the same effect. Examples include:
Aldosterone antagonists, such as spironolactone (Aldactone)
Potassium-sparing diuretics (water pills), such as triamterene (Dyrenium)
Keep in mind that many over-the-counter (OTC) supplements and multivitamins contain potassium. And even a diet high in potassium or using salt substitutes that contain potassium can raise your risk of high potassium levels.
Before and during treatment with Entresto, your prescriber should check your potassium levels. If they’re too high, they may make changes to your medication regimen. If you experience symptoms of high potassium — such as tiredness, muscle weakness, and a numbness or tingling sensation — let your prescriber know. In rare cases, high potassium can cause abnormal heart rhythms.
5. NSAIDs such as ibuprofen
Entresto also interacts with NSAIDs. Examples of NSAIDs include:
Naproxen (Aleve, Naprosyn)
Diclofenac (Cambia, Cataflam)
Celecoxib (Celebrex, Elyxyb)
Taking Entresto and an NSAID at the same time raises your risk for kidney problems. This interaction can lead to acute (sudden) kidney damage, although this is rare. Symptoms include peeing very little or not at all, feeling weak or tired, and having swelling in your ankles and feet. If you experience kidney problems due to this interaction, your prescriber will likely recommend stopping your NSAID or Entresto (or both).
What’s more, NSAIDs can increase blood pressure and raise the risk of heart attacks. This is especially true if you take NSAIDs at high doses or for long periods of time.
NSAIDs can be used to manage chronic inflammatory conditions. So it’s possible you may need to take both Entresto and an NSAID. But your prescriber should help you find the lowest NSAID dose that helps manage your symptoms. This helps lower the risks of this Entresto interaction.
Before and during treatment with Entresto, your prescriber will monitor your kidney function with blood tests. If your kidneys aren’t working as well as expected, they may lower the dosage of one or more of your medications. Your prescriber will also likely monitor your heart health closely if this Entreto interaction can’t be avoided.
Keep in mind: NSAIDs are in many OTC products, including cough and cold medications. For example, ibuprofen is in several OTC products, such as Advil PM (ibuprofen / diphenhydramine) and Advil Cold and Sinus (ibuprofen / pseudoephedrine). Read all OTC labels or ask a pharmacist if an OTC product is safe to combine with Entresto.
6. Lithium
Entresto also interacts with lithium, a mood stabilizer. Entresto can cause lithium levels to rise in your blood. High lithium levels can cause many side effects, including vomiting, confusion, and seizures. In severe cases, it can be life-threatening.
It’s possible that you’ll need to take both Entresto and lithium. In this case, your prescriber should closely monitor your blood lithium levels. If your levels go too high, they’ll likely lower your lithium dosage.
Frequently asked questions
There are no foods you need to completely avoid while taking Entresto. But you may need to be cautious of how much potassium you consume. Potassium-rich foods include avocados, dried apricots, and lentils. Acorn squash, raisins, and baked potatoes also contain a lot of this electrolyte. Discuss whether you should make dietary changes with your healthcare team while taking Entresto.
Yes, you can take Tylenol (acetaminophen) and Entresto at the same time, as long as you can safely take each medication on its own. These two medications don’t interact.
Yes, you can take Cialis (tadalafil) with Entresto. They don't interact with each other. But erectile dysfunction pills may not be safe for people with certain heart conditions. So make sure your Cialis prescriber knows your health history before you take it.
There are no foods you need to completely avoid while taking Entresto. But you may need to be cautious of how much potassium you consume. Potassium-rich foods include avocados, dried apricots, and lentils. Acorn squash, raisins, and baked potatoes also contain a lot of this electrolyte. Discuss whether you should make dietary changes with your healthcare team while taking Entresto.
Yes, you can take Tylenol (acetaminophen) and Entresto at the same time, as long as you can safely take each medication on its own. These two medications don’t interact.
Yes, you can take Cialis (tadalafil) with Entresto. They don't interact with each other. But erectile dysfunction pills may not be safe for people with certain heart conditions. So make sure your Cialis prescriber knows your health history before you take it.
The bottom line
Entresto (sacubitril / valsartan) is a heart failure medication. It interacts with several other medications. For example, you shouldn’t take Entresto with angiotensin-converting enzyme (ACE) inhibitors such as lisinopril (Zestril, Qbrelis). You also shouldn't take Entresto with angiotensin II receptor blockers (ARBs) such as valsartan (Cozaar).
Entresto also interacts with lithium (Lithobid) and nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil, Motrin). It interacts with medications that raise potassium levels, such as spironolactone (Aldactone) and potassium supplements, as well.
Review your medication list with your prescriber and pharmacist before taking Entresto. They can determine if a possible Entresto interaction exists and what to do next.
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References
American College of Cardiology. (2015). FDA approves new heart failure drug.
American Kidney Fund. (2025). Acute kidney injury (AKI) symptoms, treatment and prevention.
Heidenreich, P. A., et al. (2022). 2022 AHA/ACC/HFSA guideline for the management of heart failure: Executive summary: A report of the American College of Cardiology/American Heart Association joint committee on clinical practice guidelines. Circulation.
LXO US. (2023). Tekturna- aliskiren hemifumarate tablet, film coated [package insert].
Nicolas, D., et al. (2024). Sacubitril-valsartan. StatPearls.
Novartis Pharmaceuticals Corporation. (2024). Entresto - sacubitril and valsartan tablet, film coated [package insert].
