Sacubitril

in ENTRESTO

Open Sacubitril in the interactive console ↗

What it isNeprilysin inhibitor, given only with valsartan; heart failure with reduced ejection fraction.

Why this oneSuperior to an ACE inhibitor for mortality in HFrEF, which is why it replaced enalapril as the standard.

What limits itA 36-hour washout from an ACE inhibitor is mandatory or angioedema risk compounds. Hypotension and hyperkalemia; it raises natriuretic peptides, so BNP becomes uninterpretable.

FDA-approved for

heart failure (2015)

FDA label

Read the full label on DailyMed ↗

BOXED WARNING Fetal toxicity — discontinue as soon as pregnancy is detected; drugs acting on the renin-angiotensin system can cause fetal injury and death.

FDA dosing	Population	Start	Target	Max
Chronic heart failure (reduce CV death and HF hospitalization)	Adults	49/51 mg BID	97/103 mg BID	97/103 mg BID
Heart failure	Pediatric >=1 yr	weight-based (e.g. <40 kg 1.6 mg/kg BID; >=50 kg 49/51 mg BID)	weight-based titration	97/103 mg BID (>=50 kg)

Titration Adults: double the dose every 2–4 weeks to target as tolerated. Pediatric: adjust every 2 weeks.

Renal No adjustment in mild-moderate impairment. Severe (eGFR <30): halve the starting dose (24/26 mg BID).

Hepatic Moderate: halve the starting dose (24/26 mg BID). Severe: use not recommended.

Reduce the starting dose to half in ACEi/ARB-naive or previously low-dose patients, severe renal impairment, or moderate hepatic impairment.

Instructions

Take twice daily
Do not co-administer with an ACE inhibitor; allow a 36-hour washout when switching to or from an ACEi
An oral suspension can be substituted for patients unable to swallow tablets

Contraindications

History of angioedema related to previous ACEi or ARB therapy
Concomitant use of ACE inhibitors (or within 36 hours of switching)
Concomitant aliskiren in patients with diabetes

Cautions

Angioedema
Hypotension
Impaired renal function
Hyperkalemia
Fetal toxicity

Adverse reactions

Hypotension
Hyperkalemia
Renal dysfunction
Cough
Dizziness

Pregnancy Can cause fetal harm; discontinue when pregnancy is detected.

Lactation Undefined

⚠ BOXED WARNING

Fetal toxicity

Classes and tags

Clinical profile

Direct muscarinic antagonism0 / 4

Mechanism of action: Sacubitril ballicule

Sacubitril ballicule: receptor binding, kinetics and half-life diagram

Open Sacubitril in the interactive console ↗

Memory aids: mascots and interaction avatars

Sacubitril ENTRESTO mascot mnemonic cartoon — **“Sack your bit drill”**
with valsartan in ENTRESTO)
not available as an individual standalone medication

Box: minimal PK interactions

Open Sacubitril in the interactive console ↗