What are the side effects of Entresto (sacubitril and valsartan)?

Entresto Side Effects

Most Common and Serious Side Effects

Entresto (sacubitril/valsartan) most commonly causes symptomatic hypotension, followed by cough, dizziness, and renal dysfunction, with serious but less common risks including angioedema and hyperkalemia. 1

Primary Cardiovascular Side Effects

• Hypotension is the most frequently reported adverse effect, occurring more commonly than with ACE inhibitors or ARBs alone, particularly in patients also taking diuretics 2, 3, 1, 4

  • Manifests as dizziness, lightheadedness, or extreme fatigue 1
  • Risk is greater when combined with water pills (diuretics) 1

• Cough and dizziness are among the most common side effects reported in clinical practice 1

Serious Adverse Events Requiring Monitoring

• Angioedema (swelling of face, lips, tongue, and throat) can occur and may cause life-threatening airway obstruction 1, 4

  • Black patients have a higher risk of angioedema compared to non-Black patients 1
  • Patients with prior angioedema history face increased risk 1
  • Requires immediate discontinuation and emergency medical attention 1
  • Must allow 36-hour washout period when switching from ACE inhibitors to avoid angioedema risk 5

• Renal dysfunction is common and can progress to kidney failure 1, 6

  • Requires regular monitoring of kidney function during treatment 1
  • Despite concerns, meta-analysis shows sacubitril/valsartan actually prevents serum creatinine elevation and eGFR decline in CKD patients 7

• Hyperkalemia (elevated potassium levels) occurs commonly, though less frequently than with spironolactone 3, 1

  • Requires regular monitoring of serum potassium levels 3, 1
  • Real-world data shows acceptable risk profile without significant increase in hyperkalemia rates 6

Drug Interactions

• Statin interactions may occur due to sacubitril's inhibition of OATP1B1, OATP1B3, OAT1, and OAT3 transporters 2, 3
  • Can increase atorvastatin levels by up to 2-fold (Cmax) and 1.3-fold (AUC) 2
  • Lower statin doses may be considered when combined with sacubitril/valsartan 2

Safety Profile from Clinical Experience

Real-world pharmacovigilance data from 103,038 adverse events across global databases demonstrates that the composite risk of hypotension, renal dysfunction, hyperkalemia, and angioedema is acceptable and lower than other guideline-directed heart failure medications 6. The incidence of angioedema specifically remains low in clinical practice 4, 6.

Critical Monitoring Requirements

Your doctor must check the following during treatment 1:

• Blood pressure (for hypotension)
• Kidney function tests
• Serum potassium levels

Dose adjustments, temporary holds, or permanent discontinuation may be necessary based on these monitoring parameters 1.