Entresto
Entresto (sacubitril / valsartan) is a combination medication called an angiotensin receptor-neprilysin inhibitor (ARNI). It's used for heart failure in adults and children ages 1 year and older. It helps lower the risk of hospital stays and heart-related death in adults with heart failure. You usually take the medication by mouth twice a day. Entresto is available as tablets. It also comes as Entresto Sprinkle, which are capsules you open and mix the pellets inside with soft food. Side effects include low blood pressure and cough. As of early 2025, there's no generic version of this medication.
What is Entresto (sacubitril / valsartan)?
What is Entresto (sacubitril / valsartan) used for?
Heart failure in people ages 1 year or older
How Entresto (sacubitril / valsartan) works
Entresto (sacubitril / valsartan) is made of two medications that work together to treat heart failure. This combination is called an angiotensin receptor-neprilysin inhibitor (ARNI).
Sacubitril is a neprilysin inhibitor. It blocks a protein in your body called neprilysin. This stops neprilysin from breaking down substances called natriuretic peptides. It helps these natriuretic peptides stick around in the body longer. This helps relax your blood vessels and lower your blood pressure. This is important for preventing heart failure from getting worse.
Valsartan is an angiotensin receptor blocker (ARB). It works by blocking angiotensin II, a hormone that usually narrows blood vessels. By blocking this hormone, valsartan relaxes blood vessels. This lowers your blood pressure and makes it easier for more blood to get to your heart and other parts of the body.
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What are the side effects of Entresto (sacubitril / valsartan)?
Common Side Effects
- Low blood pressure (18%)
- High potassium levels (12%)
- Cough (9%)
- Dizziness (6%)
- Kidney problems (5%)
Other Side Effects
- Rash
- Itching
Serious Side Effects
- Angioedema: swelling of the eyes, face, tongue, throat, hands, feet, legs, or genitals
- Severely low blood pressure: lightheadedness, dizziness, feeling faint or very tired, confusion
- Serious kidney problems: urinating less often than usual; swelling in your feet, ankles, or hands; unexplained weight gain
- High potassium levels: nausea, tiredness, chest pain, muscle weakness, tingling or numbness, pounding heart
Source: DailyMed
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The following side effects have also been reported
Side effects that you should report to your care team as soon as possible:
- Allergic reactions or angioedema—skin rash, itching or hives, swelling of the face, eyes, lips, tongue, arms, or legs, trouble swallowing or breathing
- High potassium level—muscle weakness, fast or irregular heartbeat
- Kidney injury—decrease in the amount of urine, swelling of the ankles, hands, or feet
- Low blood pressure—dizziness, feeling faint or lightheaded, blurry vision
Side effects that usually do not require medical attention (report to your care team if they continue or are bothersome):
Pros and cons of Entresto (sacubitril / valsartan)
Pros
First-choice treatment for some people with heart failure
Can lower the risk of hospital visits related to heart failure in adults
Combines two medications into one pill for convenience
Available as tablets, oral pellets, or a prepared oral solution
Cons
Need to take twice daily
Can cause dizziness and low blood pressure
Not safe during pregnancy
Pharmacist tips for Entresto (sacubitril / valsartan)
You can take Entresto (sacubitril / valsartan) with or without food.
Tell your prescriber if you have trouble swallowing the Entresto tablets. They can help you find another option. Some pharmacies can make an oral liquid for you from the tablets. Another option is Entresto Sprinkle, which are small pellets of the medication that you can mix with soft food. Follow the specific instructions for each version of the medication.
You might feel dizzy the first few days after starting Entresto (sacubitril / valsartan) and with doses changes. This should get better or go away as your body adjusts to your new blood pressure. If you feel too dizzy or lightheaded, speak to your prescriber. They might adjust your medications.
Entresto (sacubitril / valsartan) can raise your potassium levels. This can sometimes make you feel tired, have weak muscles, or have an irregular heartbeat. Your care team might suggest eating food with a lot of potassium in moderation. Don't use salt substitutes that contain potassium in your food.
Follow a heart-healthy diet while taking Entresto (sacubitril / valsartan). Ask your care team for tips on choosing low-salt foods. This can help lower your blood pressure, lessen extra fluid in your body, and reduce some stress on your heart.
Tell your prescriber and pharmacist about all the medications you take or plan to take. Entresto (sacubitril / valsartan) can interact with other medications, which can raise your risk of side effects. This includes ACE inhibitors and ibuprofen (Advil). Your care team can check that your medications are safe to take together.
Don't take Entresto (sacubitril / valsartan) if you're pregnant. This medication can harm an unborn baby if it's taken during pregnancy. Talk to your prescriber right away if you're pregnant or thinking of getting pregnant.
Tips for the Entresto liquid prepared by the pharmacy
Store the liquid at room temperature (up to 77ºF). Don't put it in the refrigerator.
The liquid is good for 15 days. Throw the bottle away after 15 days at room temperature, even if there's leftover medication.
Make sure to shake the liquid bottle well before each time you measure out the dose. Only use an oral syringe from the pharmacy to measure the dose. Don't use regular kitchen spoons; they aren't accurate and using them can make you take the wrong dose.
Tips for the Entresto Sprinkle pellets
Entresto Sprinkle comes as capsules that contain pellets inside. Don't swallow the capsules whole. The capsules are meant to be opened.
To prepare your dose: Hold the capsule over about 1 to 2 teaspoons of soft food, like applesauce or yogurt. Gently pinch the middle of the capsule and pull the two ends apart. Be careful not to spill the pellets. Sprinkle all the pellets onto the soft food.
To take your dose: Eat all the food with the pellets on top right away. This makes sure you've taken all the medication for your dose. Don't chew or crush the pellets because it can change how the medication tastes. Throw away the empty capsule shells in the trash.
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Frequently asked questions about Entresto (sacubitril / valsartan)
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What are the risks and warnings for Entresto (sacubitril / valsartan)?
Entresto (sacubitril / valsartan) can cause some serious health issues. This risk may be even higher for certain groups. If this worries you, talk to your doctor or pharmacist about other options.
Not safe during pregnancy
Entresto (sacubitril / valsartan) can cause serious harm to an unborn baby if taken during the second or third trimester of pregnancy. If you become pregnant while taking Entresto (sacubitril / valsartan), stop taking it right away and talk to your prescriber. They can help you find a safer option.
Swelling of face, tongue, or throat (angioedema)
Risk factors: Black people | History of angioedema
Angioedema is a reaction that some people can have while taking Entresto (sacubitril / valsartan). It can happen at any time during treatment. Don't take Entresto (sacubitril / valsartan) if you've had angioedema from an ACE inhibitor or ARB before.
Angioedema can cause swelling in your face, lips, tongue, throat, or other parts of your body. Swelling of the tongue or throat can make it hard to breathe, which can be very dangerous. Get medical help right away if you see any swelling, if you have trouble breathing, or if you have stomach pain.
Low blood pressure
Risk factors: Dehydration (not enough fluid in the body) | Lots of diarrhea or vomiting | Low salt levels in the body | Taking higher doses of diuretics
Entresto (sacubitril / valsartan) lowers your blood pressure. This can sometimes make you feel dizzy, tired, or lightheaded.
These side effects are more common when you first start taking this medication. They can also happen when your dose goes up. The risk is higher if you're dehydrated or have problems that cause dehydration, like lots of diarrhea or vomiting.
Make sure to stay well-hydrated while taking Entresto (sacubitril / valsartan). If you feel dizzy, sit down slowly while holding onto something. Tell your prescriber if you feel lightheaded, faint, tired, or confused while taking this medication. If needed, they can adjust your treatment plan. If you fall and hit your head, get medical help right away.
Kidney problems
Risk factors: Severe heart failure | Kidney problems | Not enough fluid in your body | Taking other medications that can cause kidney damage
Entresto (sacubitril / valsartan) can affect your kidneys and cause them to not work as well. This can happen to anyone. But the effects can be more severe in people with heart failure or kidney problems. They can also be more severe for those who take medications that can worsen kidney function.
Your prescriber might order lab tests every so often while you're taking Entresto (sacubitril / valsartan). These tests help check that your kidneys are healthy. Tell your prescriber if you're urinating less often than usual. This could be a sign that your kidneys aren't working as well.
If you have kidney problems or if they get worse, your prescriber might lower your dose or stop Entresto (sacubitril / valsartan).
High potassium levels
Risk factors: Severe kidney problems | Diabetes | Low aldosterone levels | High potassium diet | Taking other medications that can raise potassium levels
Entresto (sacubitril / valsartan) can cause high potassium levels. This can be dangerous if left untreated. The risk is higher if you have severe kidney problems. You also might be at risk if you take other medications, like spironolactone (Aldactone) or eplerenone (Inspra).
Tell your healthcare team right away if you have signs of high potassium levels while taking Entresto (sacubitril / valsartan). Watch for nausea, muscle weakness, or an irregular heartbeat. You might need to get your potassium levels checked. If they're too high, your prescriber might lower your dose or pause your treatment.
Entresto (sacubitril / valsartan) dosage forms
Typical dosing for Entresto (sacubitril / valsartan)
Adults: The typical starting dose is 49 mg/51 mg (sacubitril/valsartan) by mouth twice a day. After 2 to 4 weeks, your prescriber will raise your dose. The typical maintenance dose is 97 mg/103 mg (sacubitril/valsartan) twice a day.
Children: The dose is based on your child's body weight. If needed, the prescriber will adjust the dose every 2 weeks.
Entresto tablets
Weigh 110 lbs or more: The typical starting dose is 49 mg/51 mg (sacubitril/valsartan) by mouth twice a day. The typical maintenance dose is 97 mg/103 mg (sacubitril/valsartan) twice a day.
Weigh 88 lbs to less than 110 lbs: The typical starting dose is 24 mg/26 mg (sacubitril/valsartan) by mouth twice a day. The typical maintenance dose is 72 mg/78 mg (sacubitril/valsartan) twice a day.
Weigh less than 88 lbs (given as a liquid made by the pharmacy): The typical starting dose is 1.6 mg/kg by mouth twice a day. The typical maintenance dose is 3.1 mg/kg twice a day. The dose is calculated from the combined amount of sacubitril and valsartan in the oral liquid.
Entresto Sprinkle (oral pellets)
Entresto Sprinkle comes in capsules that you open to get the small oral pellets inside. The prescriber will tell you how many capsules to use for the dose.
Weigh 75 lbs to less than 110 lbs: The typical starting dose is 30 mg/32 mg (sacubitril/valsartan) by mouth twice a day. The typical maintenance dose is 60 mg/64 mg (sacubitril/valsartan) twice a day.
Weigh 57 lbs to less than 75 lbs: The typical starting dose is 24 mg/24 mg (sacubitril/valsartan) by mouth twice a day. The typical maintenance dose is 45 mg/48 mg (sacubitril/valsartan) twice a day.
Weigh 42 lbs to less than 57 lbs: The typical starting dose is 18 mg/18 mg (sacubitril/valsartan) by mouth twice a day. The typical maintenance dose is 30 mg/32 mg (sacubitril/valsartan) twice a day.
Weigh 29 lbs to less than 42 lbs: The typical starting dose is 12 mg/12 mg (sacubitril/valsartan) by mouth twice a day. The typical maintenance dose is 24 mg/24 mg (sacubitril/valsartan) twice a day.
Note: Your dose might differ if you have kidney or liver problems. It also might differ if you're not currently taking, or were taking a low dose of, an ACE inhibitor or ARB.
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Entresto (sacubitril / valsartan) contraindications
History of angioedema from an ACE inhibitor or ARB
Have taken an ACE inhibitor within 36 hours of Entresto (sacubitril / valsartan)
Have diabetes and also take aliskiren (Tekturna)
Allergy to sacubitril or valsartan (Diovan)
What are alternatives to Entresto (sacubitril / valsartan)?
Heart failure in people ages 1 year or older
High blood pressure
Heart failure
Lower the risk for death after a heart attack
High blood pressure in adults and children
Lower the risk of hospitalization for heart failure in adults
Lower the risk of death after a heart attack in adults
What is the latest news about Entresto (sacubitril / valsartan)?
Entresto (sacubitril / valsartan) images
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References
Best studies we foundAmerican Heart Association. (2023). Ejection fraction heart failure measurement.
Amin, O. A., et al. (2021). The impact of discontinuation of sacubitril-valsartan and shifting to angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in patients with heart failure with reduced ejection fraction. Anatolian Journal of Cardiology.
Desai, A. S., et al. (2017). Reduced risk of hyperkalemia during treatment of heart failure With mineralocorticoid receptor antagonists by use of sacubitril/valsartan compared with enalapril. JAMA Cardiology.
Fernandez, J. (2024). Angioedema. Merck Manual Consumer Version.
Heidenreich, P. A., et al. (2022). 2022 AHA/ACC/HFSA guideline for the management of heart failure: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation.
Lee, N. S., et al. (2016). Current understanding of the compensatory actions of cardiac natriuretic peptides in cardiac failure: A clinical perspective. Cardiac Failure Review.
Mohebi, R., et al. (2022). Dose-response to sacubitril/valsartan in patients with heart failure and reduced ejection fraction. Journal of the American College of Cardiology.
Montford, J. R., et al. (2017). How dangerous is hyperkalemia? Journal of the American Society of Nephrology.
Nicolas, D., et al. (2024). Sacubitril-valsartan. StatPearls.
Novartis Pharmaceuticals Corporation. (2025). Entresto- sacubitril and valsartan tablet, film coated; sacubitril and valsartan pellet [package insert]. DailyMed.
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