What is the best course of action for a patient with heart failure experiencing nasal prurigo while taking sacubitril-valsartan (Entresto)?

Management of Nasal Pruritus in Patients Taking Sacubitril-Valsartan

Nasal pruritus is a rare but documented adverse effect of sacubitril-valsartan that significantly impacts quality of life and typically requires discontinuation of the medication, as it does not respond to antihistamines and resolves completely within weeks of stopping the drug. 1

Recognition and Clinical Presentation

• Nasal pruritus specifically affecting the nasal septum has been reported in patients 3-6 months after initiating sacubitril-valsartan 1
• This adverse effect is not listed in the official product information but has been documented in case series 1
• The pruritus is persistent and refractory to antihistamine therapy, distinguishing it from typical allergic rhinitis 1
• Despite the proven mortality and morbidity benefits of sacubitril-valsartan in HFrEF, the constant nasal pruritus can severely impact quality of life 1

Management Algorithm

Step 1: Confirm the Diagnosis

• Verify the temporal relationship between sacubitril-valsartan initiation and symptom onset 1
• Rule out other causes of nasal pruritus (allergic rhinitis, environmental irritants, other medications) 1
• Document that antihistamines have been ineffective 1

Step 2: Assess Heart Failure Status

• Determine current NYHA class and ejection fraction 2
• Review whether the patient is on optimal guideline-directed medical therapy (GDMT) including beta-blockers and mineralocorticoid receptor antagonists 2
• Evaluate recent hospitalizations and symptom control 2

Step 3: Decision Point - Continue vs. Discontinue

Given that nasal pruritus does not respond to symptomatic treatment and significantly impairs quality of life, discontinuation is warranted 1. This prioritizes the patient's quality of life outcome, even though sacubitril-valsartan provides mortality benefit.

Step 4: Transition Strategy After Discontinuation

Switch to an ACE inhibitor or ARB as replacement therapy:

• Observe a 36-hour washout period before starting an ACE inhibitor to avoid angioedema risk 2
• No washout period is required when switching to an ARB 3
• Start with enalapril 2.5-5 mg twice daily or equivalent ACE inhibitor, titrating to target doses 2
• Alternatively, use valsartan 40-80 mg twice daily or equivalent ARB if ACE inhibitor is not tolerated 2

Step 5: Optimize Alternative GDMT

Since the patient will lose the mortality benefit of sacubitril-valsartan, maximize other evidence-based therapies:

• Ensure beta-blocker is at target dose (carvedilol 25 mg twice daily, metoprolol succinate 200 mg daily, or bisoprolol 10 mg daily) 2
• Confirm mineralocorticoid receptor antagonist use (spironolactone 25-50 mg daily or eplerenone 50 mg daily) 2
• Add an SGLT2 inhibitor (dapagliflozin 10 mg daily or empagliflozin 10 mg daily) to reduce hospitalization and death risk 3

Step 6: Monitor for Resolution

• Complete resolution of nasal pruritus typically occurs within 3-6 months of discontinuation 1
• Follow up at 2-4 weeks to confirm symptom improvement 1
• Reassess heart failure status and adjust other medications as needed 2

Important Caveats

• Do not attempt dose reduction of sacubitril-valsartan as a strategy to manage nasal pruritus, as the case series showed patients required complete discontinuation for symptom resolution 1
• This is a reversible adverse effect, so permanent documentation in the medical record is essential to prevent future re-challenge 1
• The decision to discontinue sacubitril-valsartan for nasal pruritus represents a trade-off between proven mortality benefit (20% reduction in cardiovascular death or HF hospitalization) and quality of life 2, 1
• Many physicians are unaware of this adverse effect, so education about this presentation is important for early recognition 1

Alternative Consideration

If the patient has borderline indications for sacubitril-valsartan (well-controlled symptoms, high baseline blood pressure, or recent LVEF improvement), the decision to discontinue is more straightforward 2. However, if the patient has advanced HF (NYHA class III-IV, recent hospitalizations, or very low EF), the mortality benefit may outweigh quality of life concerns, though this scenario is unlikely given that patients in the case series all chose discontinuation 1.