Entresto

Entresto is a prescription medicine used to reduce the risk of death and hospitalization in people with chronic heart failure.

Entresto is usually used with other heart failure therapies, instead of an ACE inhibitor or other ARB therapy.

Heart failure occurs when the heart is weak and cannot pump enough blood to the lungs and the rest of the body.

Entresto can harm or cause death to unborn babies. Talk to your doctor about alternative treatments for heart failure if you plan to become pregnant. If you become pregnant while taking Entresto, notify your doctor immediately.

It is unknown if Entresto is safe and effective in children.

Do not take Entresto if you:

• are allergic to sacubitril or valsartan or any ingredient in Entresto. See the end of this Patient Information leaflet for a complete list of ingredients in Entresto.
• have had an allergic reaction including swelling of the face, lips, tongue, throat or trouble breathing while taking an ACE inhibitor or angiotensin II receptor blocker (ARB).
• take an ACE inhibitor medicine. Refrain from taking Entresto for at least 36 hours before or after taking an ACE inhibitor medicine. Consult your doctor or pharmacist if you are unsure if you take an ACE inhibitor medicine.
• have diabetes and take a medicine containing aliskiren.

Before taking Entresto, inform your doctor about all your medical conditions, including if you:

• have kidney or liver problems.

What are the side effects of Entresto?

WARNING

Fetal Toxicity

• When pregnancy is detected, discontinue Entresto as soon as possible.
• Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.

Entresto may cause serious side effects including:

• Serious allergic reactions causing swelling of the face, lips, tongue, and throat (angioedema) that may cause trouble breathing and death. Seek emergency medical help immediately if you experience symptoms of angioedema or trouble breathing. Do not take Entresto again if you have had angioedema while taking Entresto.
• Black people who take Entresto may have a higher risk of experiencing angioedema compared to non-Black individuals.
• Individuals who have experienced angioedema prior to taking Entresto may have a higher risk of experiencing angioedema compared to those who have not.
• Low blood pressure (hypotension). Low blood pressure may be more common if you also take water pills. Contact your doctor if you become dizzy or lightheaded, or if you have extreme fatigue.
• Kidney problems. Your doctor will monitor your kidney function during your treatment with Entresto. If there are changes in your kidney function tests, you may require a lower dose of Entresto or need to temporarily stop taking it.
• Increased potassium levels in your blood. Your doctor will check your potassium blood level during your treatment with Entresto.

These are not all the possible side effects of Entresto. Contact your doctor for medical advice regarding side effects. You may report side effects to the FDA at 1-800-FDA-1088.

What is the dosage of Entresto?

• Entresto reduces the risk of cardiovascular death and heart failure hospitalization in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.
• Entresto is typically administered alongside other heart failure therapies, instead of an ACE inhibitor or other ARB.
• Do not use Entresto concurrently with an ACE inhibitor. If switching from an ACE inhibitor to Entresto, allow a washout period of 36 hours between administering the two drugs.
• The recommended starting dose of Entresto is 49/51 mg twice daily.
• After 2 to 4 weeks, double the dose of Entresto to achieve the target maintenance dose of 97/103 mg twice daily, as tolerated by the patient.

Dose Adjustment for Patients Not Taking an ACE Inhibitor or ARB or Previously Taking Low Doses of These Agents

A starting dose of 24/26 mg twice daily is recommended for patients not currently taking an ACE inhibitor or an ARB and for patients previously taking low doses of these agents. Double the dose of Entresto every 2 to 4 weeks to achieve the target maintenance dose of 97/103 mg twice daily, as tolerated by the patient.

Dose Adjustment for Severe Renal Impairment

No starting dose adjustment is necessary for mild or moderate renal impairment.

Dose Adjustment for Hepatic Impairment

A starting dose of 24/26 mg twice daily is recommended for patients with moderate hepatic impairment (Child-Pugh B classification). Double the dose of Entresto every 2 to 4 weeks to achieve the target maintenance dose of 97/103 mg twice daily, as tolerated by the patient.

No starting dose adjustment is necessary for mild hepatic impairment.

Use in patients with severe hepatic impairment is not recommended.

What drugs interact with Entresto?

Dual Blockade of The Renin-Angiotensin-Aldosterone System

Concomitant use of Entresto with an ACE inhibitor is contraindicated due to the increased risk of angioedema.

Avoid using Entresto with an ARB, as Entresto contains the angiotensin II receptor blocker valsartan.

The concomitant use of Entresto with aliskiren is contraindicated in patients with diabetes. Avoid its use in patients with renal impairment (eGFR < 60 mL/min/1.73 m²).

Potassium-Sparing Diuretics

Like other drugs that block angiotensin II or its effects, concomitant use of potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium may lead to increases in serum potassium levels.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors)

In elderly patients, those who are volume-depleted (including those on diuretic therapy), or those with compromised renal function, concomitant use of NSAIDs, including COX-2 inhibitors, with Entresto may result in worsened renal function, including possible acute renal failure. These effects are typically reversible. Monitor renal function periodically.

Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists. Monitor serum lithium levels during concomitant use with Entresto.

Pregnancy and breastfeeding

Entresto can cause harm to the fetus when administered to pregnant women. The use of renin-angiotensin system drugs during the second and third trimesters of pregnancy reduces fetal renal function and elevates fetal and neonatal morbidity and mortality.

Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive drugs in the first trimester have not differentiated drugs affecting the renin-angiotensin system from other antihypertensive agents. In animal reproduction studies, Entresto treatment during organogenesis resulted in increased embryo-fetal lethality in rats and rabbits and teratogenicity in rabbits.

Consider alternative drug treatment and discontinue Entresto when pregnancy is detected. However, if there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system, and if the drug is considered life-saving for the mother, advise pregnant women of the potential risk to the fetus.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the general U.S. population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

There is no information regarding the presence of sacubitril/valsartan in human milk, its effects on the breastfed infant, or its effects on milk production. Sacubitril/valsartan is present in rat milk. Due to the potential for serious adverse reactions in breastfed infants from exposure to sacubitril/valsartan, advise nursing women that breastfeeding is not recommended during treatment with Entresto.

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Summary

Entresto is a prescription medicine that reduces the risk of death and hospitalization in people with chronic heart failure. It can be combined with other heart failure therapies, instead of an ACE inhibitor or other ARB therapy. Do not take Entresto if you are pregnant, as it can harm or cause death to the unborn baby. The safety and effectiveness of Entresto in children are unknown.