Sacubitril
in ENTRESTO
Pronunciation: sa-KOO-bi-tril
“Sack your bit drill”
with valsartan in ENTRESTO)
not available as an individual standalone medication
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 ↗
| 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
Available strengths
- tab 24/26, 49/51, 97/103 mg
- cap 6/6, 15/16 mg
- pellet 6/6, 15/16 mg
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
Cost
⚠ BOXED WARNING
- Fetal toxicity
Classes and tags
Clinical profile
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