Entresto

Adult Heart Failure

Entresto is primarily used to treat adults with chronic heart failure. It is often prescribed for patients whose heart muscle is weakened and cannot pump blood effectively to the rest of the body, a condition known as heart failure with reduced ejection fraction. It may also be used in certain patients with heart failure who have a preserved ejection fraction, particularly those whose heart function is below normal levels.

Pediatric Heart Failure

This medication is also approved for use in children and adolescents aged one year and older who have symptomatic heart failure. In these patients, it helps manage the symptoms and progression of the condition.

Treatment Goals

The main objectives of using Entresto include:

• Reducing the risk of death due to cardiovascular issues.
• Lowering the likelihood of being hospitalized for worsening heart failure symptoms.
• Improving the heart's ability to pump blood more efficiently over time.

Entresto is typically used as a replacement for other types of blood pressure or heart medications, such as ACE inhibitors or ARBs, and is often part of a comprehensive treatment plan that includes other heart failure therapies.

Mechanism of Action

Entresto contains two active ingredients, sacubitril and valsartan, which work together in different ways to manage heart failure. This combination is known as an angiotensin receptor-neprilysin inhibitor (ARNI).

Sacubitril

Sacubitril is a neprilysin inhibitor. It works by blocking an enzyme called neprilysin, which is responsible for breaking down natural substances in the body that help lower blood pressure and reduce fluid buildup. By blocking this enzyme, sacubitril allows these beneficial substances to remain active longer, helping to relax blood vessels and decrease the amount of sodium and water the body retains.

Valsartan

Valsartan is an angiotensin II receptor blocker (ARB). It blocks the action of a hormone called angiotensin II, which causes blood vessels to tighten and narrow. By preventing this hormone from working, valsartan helps blood vessels stay relaxed and open, which lowers blood pressure and makes it easier for the heart to pump blood throughout the body.

Combined Effects

By using two different pathways, Entresto helps to:

• Reduce the workload on a weakened heart.
• Lower blood pressure.
• Decrease the buildup of excess salt and water in the body.
• Improve the heart's overall ability to circulate blood.

Common Side Effects

Many people using Entresto experience mild side effects as their body adjusts to the medication. Common symptoms include:

• Dizziness or lightheadedness, especially when standing up
• Cough
• Low blood pressure (hypotension)
• High potassium levels (hyperkalemia)
• Fatigue or tiredness

Serious Side Effects

Some side effects require prompt medical evaluation. Contact a healthcare provider immediately if you experience:

• Angioedema: Swelling of the face, lips, tongue, or throat, which can cause difficulty breathing or swallowing.
• Kidney problems: Entresto can affect kidney function, which may lead to kidney failure in some patients.
• Severe hyperkalemia: Very high potassium levels can be dangerous and may cause muscle weakness or heart rhythm issues.
• Severe hypotension: Extreme dizziness or fainting due to very low blood pressure.

Seek emergency medical help if you show signs of a severe allergic reaction, such as hives, skin rash, or trouble breathing.

Fetal Toxicity

Entresto can cause serious injury or death to an unborn baby if taken during pregnancy. If pregnancy is detected, the medication should be discontinued as soon as possible.

Angioedema and Allergic Reactions

This medication can cause angioedema, which is a serious swelling of the face, lips, tongue, and throat that can interfere with breathing. It should not be used by individuals who have a history of angioedema related to previous treatment with an ACE inhibitor or ARB medication. Black patients may have a higher risk of experiencing this reaction.

Drug Interactions and Contraindications

• ACE Inhibitors: Entresto must not be taken at the same time as an ACE inhibitor. A 36-hour waiting period is required when switching between an ACE inhibitor and Entresto.
• Aliskiren: This medication should not be used in combination with aliskiren in patients who have diabetes.

Kidney Function and Potassium Levels

Entresto may affect kidney function or cause hyperkalemia, which is an abnormally high level of potassium in the blood. Healthcare providers typically monitor kidney function and potassium levels periodically during treatment, especially in patients with pre-existing kidney disease.

Low Blood Pressure

Symptomatic low blood pressure, or hypotension, may occur while taking this medication. This risk is higher for patients who are dehydrated or those taking diuretic medications.

Pregnancy

Entresto contains valsartan, a medication that can cause serious injury or death to an unborn baby if taken during pregnancy. This risk is highest during the second and third trimesters. If pregnancy is detected, the medication should be discontinued as soon as possible under the guidance of a healthcare professional.

Individuals who are planning to become pregnant or who could become pregnant should discuss alternative treatment options with their doctor before starting Entresto. It is important to use effective birth control while taking this medication.

Breastfeeding

It is not known if Entresto passes into human breast milk or how it might affect a nursing infant. Because of the potential for serious adverse reactions in the baby, breastfeeding is generally not recommended while using this medication. Patients should consult with their healthcare provider to decide whether to stop breastfeeding or stop taking the medication, taking into account the importance of the drug to the mother's health.

Available Forms

Entresto is provided in the following oral formats:

• Film-coated tablets: These are intended to be swallowed whole.
• Oral pellets: Also referred to as granules, these provide an alternative for patients who have difficulty swallowing tablets.

FDA Approval and Indications

Entresto, which contains a combination of sacubitril and valsartan, is approved by the U.S. Food and Drug Administration (FDA) to treat chronic heart failure in adults. It is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure. The medication is also approved for use in pediatric patients aged one year and older who have symptomatic heart failure.

Boxed Warning

The FDA has issued a boxed warning for Entresto due to the risk of fetal toxicity. Using this medication during pregnancy can cause injury or death to a developing fetus. If pregnancy is detected, Entresto should be discontinued as soon as possible under the guidance of a healthcare provider.

Safety and Regulatory History

The FDA monitors the safety of Entresto through post-marketing surveillance programs. In 2016, the agency identified potential signals of serious risks, such as hypersensitivity reactions, through the FDA Adverse Event Reporting System (FAERS). These evaluations are part of routine regulatory oversight to ensure the medication's safety profile remains well-documented for its approved uses.

Factors Influencing Cost

As a brand-name medication, Entresto may have a higher out-of-pocket cost compared to older heart failure treatments. The final price a patient pays is typically determined by several variables:

• Insurance Coverage: Most commercial insurance plans and Medicare Part D provide coverage for Entresto, but the specific copayment or coinsurance amount depends on the plan's formulary tier and the patient's deductible status.
• Pharmacy Choice: Prices can vary between retail pharmacies, mail-order services, and specialty pharmacies.
• Dosage and Quantity: The prescribed strength and the number of tablets per fill can affect the total cost.

Generic Availability

Entresto is a combination of two active ingredients: sacubitril and valsartan. While valsartan is available as a standalone generic medication, the specific combination found in Entresto is currently only available as a brand-name product in many regions. Generic versions of the combination drug may become available in the future as patent protections expire.

Financial Assistance

The manufacturer may offer savings cards or patient assistance programs to help reduce costs for eligible individuals with commercial insurance or those who meet specific income requirements. Patients are encouraged to check with their healthcare provider or the manufacturer for current programs. Additionally, some non-profit organizations provide grants to help cover the cost of chronic disease medications for those who qualify.