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# Sacubitril/valsartan

A heart failure combination of a neprilysin inhibitor and an ARB. It reduces cardiovascular deaths and hospital stays for heart failure.

Updated 2026-11-01

- Class: [Angiotensin receptor-neprilysin inhibitors (ARNI)](https://durgical.com/en/pharmacology/classes/angiotensin-receptor-neprilysin-inhibitors/)
- Enzyme: Neprilysin (neutral endopeptidase)
- ATC code: C09DX04

✂**Neprilysin (neutral endopeptidase)**Sacubitril/valsartan

ⓘ The figure shows sacubitrilat (LBQ657), the active form of sacubitril, bound to the zinc active site of human neprilysin; valsartan acts separately on the AT1 receptor.

**Target in 3D:** Neprilysin (neutral endopeptidase). PDB structure 5JMY (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/5JMY) · Drag to rotate · pinch to zoom

## Mechanism of action

Sacubitril is a prodrug that esterases turn into LBQ657, which inhibits neprilysin. Natriuretic peptides then last longer and promote sodium loss, vasodilation and less fibrosis. Valsartan blocks the AT1 receptor, cancelling the rise in angiotensin II that neprilysin inhibition would cause. Together they unload the failing heart.

- Esterases convert sacubitril to LBQ657, which inhibits neprilysin
- Natriuretic peptides last longer: sodium loss and vasodilation
- Valsartan blocks the AT1 receptor of angiotensin II
- Lower preload and afterload; less remodelling

## Pharmacokinetics

**Metabolism**
Sacubitril is converted by esterases to LBQ657; valsartan is barely metabolised

**Elimination**
LBQ657 mainly in urine; valsartan mainly in bile and faeces

## Indications

- Chronic heart failure, with the clearest benefit when ejection fraction is below normal [Heart failure →](https://durgical.com/en/conditions/heart-failure/)
- Symptomatic heart failure with left ventricular systolic dysfunction in children

## Adverse effects

### Common

- Hypotension
- Hyperkalaemia
- Cough
- Dizziness
- Rise in creatinine

### Serious (rare, important)

- Angioedema, more frequent in Black patients
- Acute kidney injury, especially with renal artery stenosis
- Fetal toxicity

## Contraindications

- Pregnancy
- History of angioedema with an ACE inhibitor or ARB
- Use with an ACE inhibitor or within 36 hours of one
- Use with aliskiren in people with diabetes

## Key interactions

**ACE inhibitors**
Much higher risk of angioedema; contraindicated

**Potassium-sparing diuretics or potassium supplements**
Hyperkalaemia

**NSAIDs**
Worse kidney function, especially in older or volume-depleted patients

**Lithium**
Lithium toxicity

## What is monitored

- Blood pressure
- Potassium and creatinine
- NT-proBNP (not BNP) to follow heart failure
- Signs of angioedema

## Administration and safety

- Given by mouth twice a day; the dose is raised step by step as blood pressure allows
- When switching from an ACE inhibitor, the ACE inhibitor is stopped and at least 36 hours pass before the first dose
- Valsartan in this combination is not dosed the same as valsartan alone: the products are not swapped

## Nursing care

- Confirm the time of the last ACE inhibitor dose before the first dose
- Check blood pressure before doses and ask about dizziness on standing
- Watch potassium and creatinine, and teach the patient that face or tongue swelling is an emergency
- Teach daily weights and what weight gain to report

## Pregnancy and breastfeeding

Contraindicated: drugs acting on the renin-angiotensin system can injure and kill the developing fetus; it is stopped as soon as pregnancy is detected.

## Memory aid

SACUBITRIL SAves the peptides, VALSARTAN guards the gate: never with an ACE inhibitor, wait 36 hours.

## Test yourself

Think of the answer, then tap the question to see it.

## Which enzyme does sacubitril inhibit, and what is its active form?

Neprilysin; sacubitril is a prodrug converted by esterases to LBQ657 (sacubitrilat).

## A patient on enalapril is switched to sacubitril/valsartan. What timing rule applies?

Enalapril is stopped and at least 36 hours pass before the first dose, to avoid angioedema.

## Why may BNP rise during treatment even if the patient improves?

BNP is a neprilysin substrate, so less of it is broken down; NT-proBNP is followed instead.

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## Related drugs

- [Valsartan](https://durgical.com/en/pharmacology/valsartan/)
- [Enalapril](https://durgical.com/en/pharmacology/enalapril/)
- [Carvedilol](https://durgical.com/en/pharmacology/carvedilol/)

## Related conditions

- [Heart failure](https://durgical.com/en/conditions/heart-failure/)

[← Back to the class: Angiotensin receptor-neprilysin inhibitors (ARNI)](https://durgical.com/en/pharmacology/classes/angiotensin-receptor-neprilysin-inhibitors/)

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [DailyMed - SACUBITRIL AND VALSARTAN tablet, film coated](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ccfa182e-8a23-42e1-9062-be2655c96208) (DailyMed (U.S. National Library of Medicine), 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=C09DX04) (WHO Collaborating Centre for Drug Statistics Methodology, 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 33 (McGraw Hill, 2023).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/pharmacology/sacubitril-valsartan/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/sacubitril-valsartan/