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What Is Sacubitril and Valsartan?

Sacubitril and valsartan is a prescription combination medication marketed under the brand name Entresto. It combines a neprilysin inhibitor with an angiotensin II receptor blocker and belongs to the angiotensin receptor-neprilysin inhibitor class. It is used to reduce cardiovascular death and hospitalization in adults with chronic heart failure and to treat certain children with symptomatic heart failure. The medication helps regulate blood vessel tone, sodium balance, and other pathways involved in cardiovascular function. It is taken orally twice daily. Sacubitril and valsartan carries a boxed warning for fetal toxicity and must not be taken with an ACE inhibitor.

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What Is Sacubitril and Valsartan?

Sacubitril and valsartan is a prescription combination medication marketed under the brand name Entresto. It combines a neprilysin inhibitor with an angiotensin II receptor blocker and belongs to the angiotensin receptor-neprilysin inhibitor class. It is used to reduce cardiovascular death and hospitalization in adults with chronic heart failure and to treat certain children with symptomatic heart failure. The medication helps regulate blood vessel tone, sodium balance, and other pathways involved in cardiovascular function. It is taken orally twice daily. Sacubitril and valsartan carries a boxed warning for fetal toxicity and must not be taken with an ACE inhibitor.

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How Does Sacubitril and Valsartan Work?

Sacubitril is converted into an active substance that inhibits neprilysin, an enzyme that breaks down several naturally occurring peptides involved in blood vessel relaxation and sodium excretion. Neprilysin inhibition increases the activity of these peptides. Valsartan blocks angiotensin II type 1 receptors, reducing the effects of angiotensin II on blood vessel constriction and aldosterone release. Together, the ingredients reduce harmful neurohormonal activity associated with heart failure and can lower cardiovascular risk in eligible patients. The combination is not the same as taking an ACE inhibitor and an angiotensin receptor blocker together. Its effects require monitoring of blood pressure, kidney function, and potassium levels.

What Type of Heart Failure Does Sacubitril and Valsartan Treat?

Sacubitril and valsartan is approved to reduce cardiovascular death and hospitalization for heart failure in adults with chronic heart failure. Clinical benefits are most clearly demonstrated in patients with a left ventricular ejection fraction below normal. It is also approved for symptomatic heart failure with systemic left ventricular systolic dysfunction in children aged one year and older. Pediatric treatment has demonstrated reductions in NT-proBNP, a biomarker associated with heart failure. A cardiologist evaluates heart function, blood pressure, kidney function, current medications, and other factors before treatment. The medication is not intended as immediate treatment for acute cardiovascular collapse.

How Should Sacubitril and Valsartan Be Taken?

Entresto is taken orally twice daily, with or without food. The recommended adult starting dose is 49 mg sacubitril and 51 mg valsartan twice daily, with the dose generally doubled after two to four weeks to a target of 97 mg/103 mg twice daily when tolerated. Patients who are not taking an ACE inhibitor or angiotensin receptor blocker, or who have previously taken low doses, may begin at 24 mg/26 mg twice daily. Pediatric dosing is weight-based, with Entresto Sprinkle oral pellets available for certain patients. A 36-hour interval is required between Entresto and an ACE inhibitor in either direction. Kidney and liver impairment may require dose adjustments.

What Are the Side Effects and Warnings of Sacubitril and Valsartan?

Common adverse effects include low blood pressure, dizziness, elevated potassium, cough, and changes in kidney function. Serious risks include angioedema, kidney impairment, and significant hyperkalemia. Entresto carries a boxed warning for fetal toxicity and must be discontinued as soon as pregnancy is recognized under medical direction. It is contraindicated in patients with certain histories of angioedema and must not be taken simultaneously with ACE inhibitors or within 36 hours of an ACE inhibitor dose. Patients with diabetes must not combine it with aliskiren. Facial or tongue swelling, difficulty breathing, fainting, or markedly reduced urination requires immediate medical attention.

Common Questions About Sacubitril and Valsartan

Is sacubitril and valsartan the same as Entresto?

Yes. Entresto is the brand name for the combination of sacubitril and valsartan, used for certain types of heart failure.

Can sacubitril and valsartan be taken with lisinopril?

No. Lisinopril is an ACE inhibitor. At least 36 hours must separate ACE inhibitor treatment and sacubitril and valsartan to reduce the risk of angioedema.

Can children take sacubitril and valsartan?

Yes. Entresto is approved for symptomatic heart failure with systemic left ventricular systolic dysfunction in children aged one year and older.

Is sacubitril and valsartan safe during pregnancy?

No. It carries a boxed warning for fetal toxicity because drugs affecting the renin-angiotensin system can seriously injure or kill a developing fetus.

References

DailyMed - ENTRESTO (sacubitril and valsartan) tablets and oral pellets. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=000dc81d-ab91-450c-8eae-8eb74e72296f. Date Accessed November 6, 2026.

Sacubitril. PubChem. https://pubchem.ncbi.nlm.nih.gov/compound/9811834. Date Accessed November 6, 2026.

Sacubitril-Valsartan. LiverTox. https://www.ncbi.nlm.nih.gov/books/NBK605173/. Date Accessed November 6, 2026.

Valsartan. PubChem. https://pubchem.ncbi.nlm.nih.gov/compound/Valsartan. Date Accessed November 6, 2026.

Valsartan and Sacubitril. MedlinePlus. https://medlineplus.gov/druginfo/meds/a615039.html. Date Accessed November 6, 2026.