BSN Tracker

sacubitril/valsartan

Brand: Entresto

⚠ BBW Prototype Drug
Drug Class: angiotensin receptor-neprilysin inhibitor (ARNI)
Drug Family: antihypertensive
Subclass: combination ARB + neprilysin inhibitor
Organ Systems: cardiovascular

Mechanism of Action

Sacubitrilat inhibits neprilysin, preventing degradation of natriuretic peptides (BNP, ANP), augmenting vasodilation, natriuresis, and anti-fibrotic effects; valsartan blocks AT1 receptors reducing vasoconstriction.

neprilysin (sacubitril)AT1 receptor (valsartan)

Indications

  • HFrEF (EF ≤40%)
  • symptomatic NYHA class II-IV heart failure

Contraindications

  • ACE inhibitor use within 36 hours (risk of angioedema)
  • history of ACE-I or ARB-induced angioedema
  • pregnancy
  • severe hepatic impairment
  • aliskiren in DM

Adverse Effects

Common

  • hypotension
  • hyperkalemia
  • renal impairment
  • dizziness

Serious

  • angioedema
  • teratogenicity
  • serious hypotension

Pharmacokinetics (ADME)

Absorption sacubitril: ~60% bioavailability; valsartan: ~23%
Distribution high protein binding both components
Metabolism sacubitril rapidly converted to sacubitrilat by esterases
Excretion sacubitrilat: 52-68% urine; valsartan: 83% feces
Half-life sacubitrilat 11.5h; valsartan 9.9h
Onset 2-4 hours
Peak 0.5h (sacubitril), 1.5h (valsartan)
Duration 12 hours (twice-daily dosing)
Protein Binding 94-97%
Vd moderate

Drug Interactions

Drug / Agent Mechanism Severity
ACE inhibitors additive angioedema risk — must wait 36 hours between switch major
potassium-sparing diuretics additive hyperkalemia major
statins (OATP1B1/B3 substrates) sacubitrilat inhibits OATP1B1/B3 transporters moderate

Nursing Considerations

  1. Ensure 36-hour washout period before switching from ACE inhibitor
  2. Monitor BP closely — higher hypotension risk than ACE inhibitors alone
  3. Monitor K+ and creatinine
  4. PARADIGM-HF: reduced CV mortality and HF hospitalizations vs enalapril
  5. First-line for HFrEF per ACC/AHA 2022 guidelines

Clinical Pearls

  • PARADIGM-HF: 20% relative risk reduction in CV death/HF hospitalization vs enalapril
  • Must wash out ACE inhibitor 36h before starting (angioedema risk)
  • Raises BNP but reduces NT-proBNP — use NT-proBNP for monitoring, not BNP

Safety Profile

Pregnancy contraindicated
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Required
TDM Not required
Guideline Update pending

Concordance Terms

Cross-referenced clinical concepts — click any term to see all content where it appears.

Angiotensin Receptor-neprilysin Inhibitor (ARNI) HFrEF (EF ≤40%) Symptomatic NYHA Class II-IV Heart Failure
← Back to Medications