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 heart failure treatment for the better. Entresto is a unique combination of two medications: sacubitril and valsartan. It’s a first-choice medication for treating heart failure.
Like all medications, Entresto has drug interactions that can affect its safety and effectiveness. Here, we’ll cover Entresto interactions you should know about.
Entresto interactions
There are several Entresto interactions to be aware of. Below, we’ve listed interactions to avoid and those requiring extra monitoring. Keep in mind that this isn’t a comprehensive list. Your prescriber will decide whether or not it’s safe to combine Entresto with an interacting medication based on your medical history. So be sure to provide them with your full medication list to review before you start taking it.
Medications to avoid while taking Entresto:
Angiotensin-converting enzyme (ACE) inhibitors, such as lisinopril (Zestril, Qbrelis)
Angiotensin II receptor blockers (ARBs), such as losartan (Cozaar)
Aliskiren (Tekturna), especially for people living with diabetes
Medications that require extra monitoring if combined with Entresto:
Medications that raise potassium levels, such as spironolactone (Aldactone)
Potassium supplements
Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil, Motrin)
Lithium (Lithobid)
Below, we’ll dig deeper into what you should know about six of the most significant 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. It commonly includes the tongue, throat, and 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, which requires emergency medical treatment.
If you’re taking an ACE inhibitor, it’s recommended to stop it at least 36 hours (1.5 days) before starting Entresto to avoid this interaction.
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 of kidney problems, low blood pressure, and high potassium levels.
People with diabetes or kidney problems have an even greater risk of 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.
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 this effect. Examples include:
Aldosterone antagonists, such as spironolactone
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. They can also worsen heart failure, and typically aren’t recommended for people living with this condition. This is especially true if you take NSAIDs at high doses or for long periods of time.
NSAIDs are sometimes 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 both Advil PM (ibuprofen / diphenhydramine) and Advil Cold and Sinus (ibuprofen / pseudoephedrine). Read all OTC labels to check for NSAIDs 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.
It isn’t likely that you’ll experience withdrawal symptoms or other concerning side effects if you stop taking Entresto abruptly. But stopping Entresto without replacing it with another medication can leave your heart failure untreated. And this can lead to major problems with your heart function. So you shouldn’t stop taking Entresto without talking to your healthcare team for guidance.
There isn’t an interaction between vitamin D and Entresto. So it should be fine to take them together. But keep in mind that most people get enough vitamin D from their diet and sun exposure. And taking too much vitamin D can be harmful. So you should only take a vitamin D supplement if your prescriber recommends 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.
It isn’t likely that you’ll experience withdrawal symptoms or other concerning side effects if you stop taking Entresto abruptly. But stopping Entresto without replacing it with another medication can leave your heart failure untreated. And this can lead to major problems with your heart function. So you shouldn’t stop taking Entresto without talking to your healthcare team for guidance.
There isn’t an interaction between vitamin D and Entresto. So it should be fine to take them together. But keep in mind that most people get enough vitamin D from their diet and sun exposure. And taking too much vitamin D can be harmful. So you should only take a vitamin D supplement if your prescriber recommends 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. (2021). Infographic | Safe prescribing and use of sacubitril/valsartan (Entresto).
American Kidney Fund. (2025). Acute kidney injury (AKI) symptoms, treatment and prevention.
Heart Failure Society of America. (2015). FDA approves Entresto.
Heart Failure Society of America. (2016). New analysis of Novartis’ Entresto data shows long-term benefits on heart failure readmissions and total cardiovascular deaths.
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. (2025). Entresto - sacubitril and valsartan tablet, film coated; Entresto - sacubitril and valsartan pellet [package insert].
