Key takeaways

Entresto is a combination drug that contains sacubitril and valsartan. It is used to reduce the risk of serious cardiovascular events in people with chronic heart failure.
Common side effects of Entresto include low blood pressure, cough, dizziness, and high potassium levels. Serious side effects may include severe allergic reactions and kidney problems.
To minimize Entresto side effects, it’s recommended to take the medication as directed, stay hydrated, monitor for signs of low blood pressure, and inform healthcare providers about all medical conditions and medications.
People with hereditary angioedema, an allergy to an ARB or ACE inhibitor, or severe liver disease should not take Entresto. Also, those who are pregnant or breastfeeding should not take this medication.

Entresto is a brand-name prescription drug used to reduce the risk of serious cardiovascular events in people with chronic heart failure. It is most successful in patients with reduced ejection fraction—when the lower chambers of the heart do not pump out enough blood.

Entresto combines two drugs sacubitril and valsartan. Sacubitril belongs to a class of drugs called neprilysin inhibitors while valsartan is a common angiotensin II receptor blocker (ARB) used to treat high blood pressure. Both drugs relax blood vessels, increase blood flow and reduce blood pressure. This decreases the amount of work on the heart to pump blood, increases the amount of blood pumped out of the heart, and slows the progress of congestive heart failure. Because Entresto combines two powerful drugs, people taking it should carefully review possible side effects, restrictions, drug interactions, and other potential problems.

RELATED: What is Entresto?

Common side effects of Entresto

The most common side effects of Entresto are:

Low blood pressure (hypotension)
Cough
Dizziness
A sudden drop in blood pressure when standing up (orthostatic hypotension)
Diarrhea
Joint pain
Tiredness
Back pain
Anemia (low blood count)
Kidney problems
High blood potassium

Serious side effects of Entresto

The most serious side effects of Entresto include:

Severe high blood potassium
Severe low blood pressure
Severe kidney problems
Muscle damage
Blood disorders
Liver problems
Severe allergic reactions, especially angioedema (swelling of the lips, face, and throat)

Entresto and hypotension

The active ingredients in Entresto, sacubitril, and valsartan, both lower blood pressure by dilating blood vessels. The most common side effect, then, is blood pressure that falls too low, or hypotension. In one large clinical trial, 18% of patients taking Entresto had clinically diagnosable low blood pressure. Low blood pressure, especially if it causes symptoms, might require dose adjustments.

People taking Entresto should consult with a healthcare provider with any sign of low blood pressure such as dizziness, vision changes, fainting, or problems concentrating. Severe hypotension will require immediate medical care.

Entresto and angioedema

In a large clinical trial, approximately 0.5% of patients had a severe allergic reaction called angioedema. The incidence was considerably higher in African-American patients (2.4%). Angioedema is a potentially life-threatening allergic reaction and will require that Entresto be stopped immediately and permanently. People taking Entresto should be aware of the risk for angioedema. Symptoms of angioedema include swelling around the eyes, mouth, lips, tongue, and hands, as well as hives, trouble breathing, redness, eye irritation, and dizziness. There is a danger that swelling could close off airways. Medical attention is needed, so get emergency medical help when any of these symptoms are noticed.

Entresto and kidney problems

Valsartan, one of the active ingredients in Entresto, alters the delicate hormone system that regulates fluid levels in the blood and body. This hormone system regulates kidney activity, so some people will experience reduced kidney function. In some patients, this could evolve into renal failure, a serious side effect experienced by 5% of Entresto patients. Patients taking Entresto will require regular blood tests to gauge how much the drug is affecting kidney function.

Entresto and high potassium levels (hyperkalemia)

The kidneys also regulate the body’s levels of electrolytes like sodium and potassium. Entresto’s effects on the kidneys raise the risk for high blood potassium, or hyperkalemia, a potentially serious side effect that could cause a heart attack. Approximately 12% of people taking Entresto will have problems with high potassium levels, so watch for symptoms such as chest pain, irregular heartbeat, fast heart rate, muscle weakness, nausea, vomiting, or diarrhea.

How long do side effects last?

Most common side effects such as low blood pressure, dizziness, cough, and other temporary side effects should resolve within a day of stopping Entresto. Extremely low blood pressure or extremely high potassium levels may require supportive medical care but are usually corrected in a few hours. Various blood disorders such as low hemoglobin, low hematocrit, and other kinds of low blood counts may require a few days or weeks to return to normal. Angioedema lasts for a few days if the drug is stopped. Kidney problems caused by Entresto often get better when the drug is stopped but there could be long-term complications.

Entresto contraindications & warnings

Entresto, like any prescription drug, does have risks. Some people may not be suitable for Entresto treatment and others might require close monitoring for adverse effects.

Abuse and dependence

Entresto and its active ingredients sacubitril and valsartan are not considered to have the potential for abuse or dependence. Stopping Entresto will not cause withdrawal symptoms, but there is a risk of rebound high blood pressure if other blood pressure drugs are not being taken.

Overdose

There is little information about the consequences of an Entresto overdose, but too much Entresto will lower blood pressure. Seek medical attention if you think too much medication has been taken.

Restrictions

People allergic to any of Entresto’s active or inactive ingredients will not be given the drug. Entresto is also contraindicated in any person who has had a severe allergic reaction to blood pressure medications called angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACE inhibitors). Also, because of the risk of angioedema, Entresto is too hazardous to give to people diagnosed with hereditary angioedema. Finally, Entresto can never be taken by people with severe liver disease.

Entresto can worsen kidney disease and low blood pressure so it will be used cautiously in people with these conditions. Low blood volume or low sodium will need to be corrected before taking Entresto. Side effects will have to be monitored carefully in people who have had a recent heart attack.

Pregnancy and nursing

Entresto should not be taken by pregnant women, particularly in the second and third trimesters. The unborn baby is at risk for harm, renal failure, and death. People taking Entresto should immediately inform their healthcare provider of a pregnancy or plans to become pregnant.

Breastfeeding is not recommended when taking Entresto. It is not known if sacubitril/valsartan is present in human breast milk or if it affects a nursing infant. However, nursing women will often be advised to switch to a different medication or discontinue breastfeeding.

Children

The U.S. Food and Drug Administration (FDA) has approved Entresto for use in children as young as 1 year old for symptomatic heart failure with left ventricular dysfunction.

Seniors

Entresto is commonly prescribed to seniors using the same dosage as younger adults, but healthcare providers will monitor their blood pressure, potassium levels, and kidney function more closely.

Entresto interactions

Sacubitril/valsartan has several effects on the body: blood pressure, fluid volume, electrolyte balance, and kidney function. A number of drug interactions can add to these effects, so healthcare providers will try to avoid them or watch carefully for adverse effects.

Contraindicated: ACE inhibitors such as enalapril, benazepril, ramipril, captopril, or lisinopril are never prescribed with Entresto because of the risk for angioedema. For the same reason, people with diabetes cannot take Entresto in combination with Tekturna (aliskiren).
Cautions: Angiotensin-receptor blockers (ARBs): Valsartan belongs to a class of drugs called ARBs. Because of the risks of kidney dysfunction and hypotension, healthcare providers avoid giving two ARBs at the same time.
Potassium-sparing diuretics and potassium supplements: High potassium is a potentially serious side effect of valsartan. Diuretics (“water pills”) that do not eliminate potassium, as well as potassium supplements, increase the risk of high potassium levels when taking Entresto.
Nonsteroidal anti-inflammatory drugs (NSAIDs): Drugs like aspirin, ibuprofen, and naproxen are toxic to the kidneys and may cause reduced kidney function or kidney damage when taken with Entresto.
Blood pressure drugs: Taking Entresto with other drugs that lower blood pressure can risk hypotension, so blood pressure will have to be monitored. Medications that may cause hypotension when used with Entresto include antidepressants, antipsychotics, benzodiazepines, sedatives, and erectile dysfunction medications.

How to avoid Entresto side effects

While Entresto has few side effects, they are commonly experienced and could become serious problems. A few tips, however, can help to minimize problems when taking Entresto.

1. Take Entresto as directed

Take Entresto exactly as directed by a healthcare professional. Do not take more or less than indicated on the prescription label. Do not stop taking this medicine until after talking to a medical professional.

2. Tell the prescribing healthcare provider about all medical conditions

Side effects are typically due to underlying physical conditions, so make sure the healthcare provider prescribing Entresto has a complete medical history, particularly:

Any history of angioedema
Liver problems
Kidney problems
Pregnancy or any pregnancy plans
Breastfeeding or plans to breastfeed

3. Tell the healthcare provider about all medications being taken

Drug interactions are another major source of adverse reactions in people taking prescription drugs. It helps to keep a complete list of all prescription drugs, over-the-counter medications, dietary supplements, and herbal or alternative remedies that are taken. Always share this list with the healthcare provider prescribing a drug or filling a prescription. For Entresto, it’s important to tell the prescribing healthcare provider about:

Potassium supplements
Salt substitutes
Blood pressure medications
NSAIDs

4. Do not skip doses

For maximum heart benefits, do not miss doses. Entresto must be taken twice per day. If missing doses is a problem, a pharmacist can recommend solutions including phone apps, bottle cap alarms, daily pillboxes, and other tools that can be used to remember each day’s doses. Remember: a missed dose can be taken as soon as it’s remembered. However, if it’s almost time for the next dose, skip the missed dose and take the next dose as scheduled.

5. Watch for signs of low blood pressure

The most common side effect of Entresto is low blood pressure. Contact a healthcare provider at any sign of low blood pressure such as lightheadedness, dizziness, or fainting.

6. Drink fluids

The valsartan in Entresto can cause problems with elevated potassium levels and low blood pressure, so it’s important to stay hydrated and keep body fluids normal. Drink fluids throughout the day, but work with your healthcare provider to eat and drink the amount that is right for your health condition. Watch for signs of elevated potassium such as heart palpitations, weakness, and chest pain and come for blood tests as recommended by your provider.

Entresto side effects and how to avoid them