Entresto: What is it Used For?

Published October 2nd, 2020 by Chris Riley
Fact Checked by
Chris Riley

Approximately five million Americans are currently living with congestive heart failure, and an additional 550,000 new cases are diagnosed in the United States each year. Congestive heart failure affects people of all age groups, races, and genders, including very young children. A new medication, called Entresto, can help some people with congestive heart failure avoid hospitalization for their condition. The key to Entresto's success is one of its active ingredients, sacubitril, which is a new medication found only in Entresto. 

What Is Entresto?

Entresto is a prescription drug that is a combination of two active ingredients: sacubitril and valsartan. The U.S Food and Drug Administration (FDA) first approved Entresto as a heart failure therapy in the United States in 2015 for the treatment of heart failure, reduced ejection fraction, and systolic dysfunction in patients aged one year old and older. Entresto is still manufactured under its original patent, so no generic versions of the drug are available. Valsartan, one of the active ingredients of Entresto, belongs to a class of drugs called angiotensin II receptor blockers, or ARBs, and is a common drug used for the treatment of various heart conditions. Entresto works differently from other heart failure medications because its other active ingredient is sacubitril, which is a medication that is unique to Entresto and belongs to a class of drugs called neprilysin inhibitors. However, it is often prescribed alongside other heart disease medications such as beta blockers. 

What is Entresto Used For?

Entresto is used to treat congestive heart failure, which is also known as chronic heart failure. Specifically, Entresto is used to treat a type of heart failure that results from the heart becoming enlarged and too weak to sufficiently pump blood throughout the body.  Congestive heart failure causes people who do not pump enough blood to have blood and other fluids back up inside the lungs, abdomen, liver, and lower body, which can be life-threatening. There are four different stages of congestive heart failure, including:

  • Class I: No symptoms are experienced, and the condition can be managed through medication, lifestyle changes, and monitoring.
  • Class II: Experience shortness of breath, fatigue, and heart palpitations during normal physical activity, but feel fine during rest. The condition can still be managed through medication, lifestyle changes, and monitoring.
  • Class III: Even mild physical activity can cause shortness of breath, fatigue, and heart palpitations, but still feel ok at rest. Treatment options are limited and can be complex.
  • Class IV: Symptoms are present even at rest, and physical activity is impossible. No remaining treatment options are available. 

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How Does Entresto Work?

Entresto works differently than other prescription drugs for heart failure as the result of its combination of two active ingredients that each work in different ways. Entresto is the first and only FDA-approved medication that improves the heart’s ability to pump blood throughout the bodies of patients with a certain type of chronic heart failure; in this type of heart failure, the heart is enlarged and too weak to properly pump blood. Entresto was superior to the angiotensin-converting enzyme inhibitor Enalapril in the PARADIGM-HF when it came to decreasing risk of cardiovascular death. Entresto takes two actions to treat heart failure. First, valsartan helps to keep the blood vessels open and prevents them from narrowing, resulting in lower blood pressure and improved blood flow. Sacubitril, a neprilysin inhibitor, is a different blood pressure medication that is only found in Entresto. Sacubitril causes the levels of certain proteins in the body to rise, helping to widen the blood vessels, which lowers blood pressure by reducing sodium levels. The combination of these two actions helps to lower the risk of hospitalization due to chronic heart failure in adults and in children as young as one year of age.

How Much Does Entresto Cost?

Due to the lack of competition for Entresto, prices for the medication are still high. Some commercial plans provide coverage for Entresto, but many do not due to the medication’s new status and high cost.  Regardless of a patient’s insured status, pharmacy discount cards can be used to obtain savings on Entresto. Currently, 30 tablets of Entresto cost about 290 dollars. Patients who have commercial insurance that does not cover Entresto or who are unable to afford Entresto even with their insurance coverage may be eligible for a co-pay card offered by the manufacturer. The co-pay card is not available for patients who have Medicare, Medicaid, or insurance through any other state or federal program. The manufacturer also offers patient support programs for patients that meet certain income and medical requirements.

Are There Any Risks Associated with Entresto?

There are many benefits of taking Entresto, but use of the drug also carries risks. Risks associated with Entresto include:

  • Entresto can cause kidney problems and impaired kidney function in any patient, including those who have never experienced kidney problems before. All patients, regardless of their current kidney health, should have their kidney function and potassium levels monitored periodically while taking Entresto.
  • Black people and those who have previously experienced angioedema (swelling of the facial areas and airways) unrelated to ACE inhibitor administration may be more likely to experience an allergic reaction to Entresto.
  • Entresto should not be taken during pregnancy unless there is no alternative available, as the medication can cause severe injury and death of the fetus in pregnant women who take the medication during the second and third trimesters of pregnancy. Women who become pregnant while taking Entresto should immediately stop using the medication unless its use is deemed necessary for the mother, who should be advised of risks to the fetus. Birth defects that are caused by the use of Entresto during pregnancy include:
    • Reduced fetal renal function
    • Skeletal deformations, including skull hypoplasia
    • Hypotension
    • Fetal lung hypoplasia
    • Death
  • People taking Entresto are more likely to experience low blood pressure, as are people taking water pills.
  • Entresto can cause levels of potassium in the blood to rise (hyperkalemia), so your doctor should check your potassium level during treatment with Entresto.

What Dose of Entresto Do I Take?

The recommended starting dose for Entresto varies depending on the age of the patient, the weight of the patient, and several other factors. Entresto is available in tablet form in three different strengths of its main ingredients, sacubitril and valsartan, including a low dose of 24 mg/26 mg, moderate dose 49 mg/51 mg, and 97 mg/103 mg.

Adults taking Entresto for heart failure typically start at a dose of 49 mg/51 mg of sacubitril/valsartan taken twice per day. The maintenance dose for the majority of patients is 97 mg/103 mg taken twice per day, and most patients reach this mark after two to four weeks. Some patients may adjust to the medication more quickly, while others may need more time to build up tolerance of the drug. 

When taken by patients aged one year and older for chronic heart failure, the dosage of Entresto varies by weight. Children take the recommended dose of Entresto twice daily, and most patients should have their dosages adjusted once every two weeks. Pediatric patients weighing less than 40 kg start at a dose of 1.6 mg/kg and gradually increase their dosages to 2.3 mg/kg and 3.1 mg/kg, respectively. Pediatric patients weighing at least 40 kg but less than 50 kg will begin taking the 24 mg/26 mg dose, then step up to the 49 mg/51 mg dose, ultimately reaching 72 mg/78 mg. Pediatric patients who weigh over 50 kg start at a dose of 49 mg/51 mg, then increase to a dose of 72 mg/78 mg and finally to 97 mg/103 mg.

What Are the Side Effects of Entresto?

Side effects associated with Entresto are considered either common or serious. Common side effects associated with Entresto include:

  • Cough
  • Low blood pressure/symptomatic hypotension (increased risk with activated renin-angiotensin-aldosterone system)
  • High potassium
  • Dizziness
  • Kidney problems

Some side effects of Entresto do require medical attention. Check with your health care provider immediately if you experience any of the following serious side effects while taking Entresto:

  • Kidney problems, as evidenced by a change in the amount of urine produced
  • Serious allergic reaction, as indicated by swelling of the face, lips, tongue, and throat
  • Low blood pressure or hypotension
  • Increased potassium levels in the blood (hyperkalemia)

Who Should Not Take Entresto?

Patients who are allergic to any of the ingredients in Entresto, including sacubitril or valsartan,  should not take Entresto. Patients with a history of any of the following also should not take Entresto:

  • Currently taking an ACE inhibitor medicine (Entresto usually take the place of an ace inhibitor)
  • Angioedema (swelling of the face/lips tongue/throat) or difficulty breathing while taking medications called ACE inhibitors or ARBs
  • Have diabetes and are currently taking a medication that contains Aliskiren
  • Currently pregnant or planning to become pregnant

Patients who are pregnant or planning to become pregnant or are breastfeeding or planning to breastfeed should not take Entresto, as the medication can cause severe injury or death to the unborn baby. Patients with current kidney or renal impairment problems, acute renal failure, or who have a history of angioedema/hereditary angioedema should speak to their doctor before taking Entresto. 

Entresto may have drug interactions with concomitant use of prescription and over the counter medications, as well as vitamins and herbal supplements. Patients should be sure to give their pharmacist and doctor a complete record of everything they are taking, particularly as it pertains to nonsteroidal anti-inflammatory drugs (NSAIDs), medications for high blood pressure or heart problems, potassium supplements, salt substitutes, lithium, ACE inhibitors, ARBs, or aliskiren.








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Published October 2nd, 2020 by Chris Riley
Fact Checked by
Chris Riley

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