Can Entresto (sacubitril and valsartan) cause blue discoloration of the feet?

Entresto (Sacubitril/Valsartan) and Blue Discoloration of the Feet

There is no evidence that Entresto (sacubitril/valsartan) directly causes blue discoloration of the feet. Based on available guidelines and drug information, this symptom is not listed as a known side effect of this medication.

Understanding Entresto and Its Side Effects

Entresto is a combination medication containing:

• Sacubitril (neprilysin inhibitor)
• Valsartan (angiotensin receptor blocker)

It is primarily indicated for:

• Heart failure with reduced ejection fraction (HFrEF)
• Reducing cardiovascular death and hospitalization in NYHA class II-IV heart failure patients 1

Known Side Effects of Entresto

The most common documented side effects include:

• Hypotension (most common) 2
• Hyperkalemia
• Acute renal failure
• Modest changes in lipid profile (decreases in triglycerides, increases in HDL-C and LDL-C) 1

Potential Causes of Blue Discoloration in Heart Failure Patients

If a patient on Entresto experiences blue discoloration of the feet, consider these more likely explanations:

1. Peripheral Circulation Issues:

   • Heart failure itself can cause poor peripheral circulation
   • Reduced cardiac output may lead to cyanosis in extremities

2. Medication-Related Hypotension:

   • Entresto can cause hypotension 1, 2
   • Severe hypotension might reduce peripheral perfusion, potentially causing bluish discoloration

3. Other Medications:

   • Calcium channel blockers (particularly dihydropyridines) can cause pedal edema 1
   • When combined with poor circulation, edema might contribute to discoloration

Clinical Approach for Patients with Blue Feet on Entresto

1. Assess Cardiovascular Status:

   • Check blood pressure (Entresto can cause hypotension)
   • Evaluate for signs of worsening heart failure
   • Assess peripheral pulses and capillary refill

2. Review Medication Regimen:

   • Check for drug interactions (particularly with statins, as Entresto can affect OATP1B1, OATP1B3, OAT1, and OAT3 transporters) 1
   • Review other medications that might cause peripheral edema

3. Consider Dosage Adjustment:

   • Initial dosing of Entresto is typically 49/51 mg twice daily
   • Maximum dose is 97/103 mg twice daily 1
   • Lower doses may be needed if hypotension is present

Important Considerations

• Do not combine Entresto with:

  • ACE inhibitors (must wait 36 hours after discontinuing ACE inhibitor before starting Entresto)
  • Other ARBs
  • Aliskiren 1

• Monitor for:

  • Hyperkalemia
  • Renal function changes
  • Blood pressure changes

Conclusion

While blue discoloration of the feet is not a documented direct side effect of Entresto, it may be related to the hemodynamic effects of the medication (particularly hypotension) or underlying heart failure. If this symptom appears, a thorough cardiovascular assessment is warranted to determine if it represents worsening heart failure or a vascular issue requiring intervention.