What is the recommended washout period when switching from losartan (Angiotensin II Receptor Antagonist) to Entresto (sacubitril/valsartan)?

Washout Period When Switching from Losartan to Entresto

No washout period is required when switching from losartan (an ARB) to Entresto (sacubitril/valsartan), and the transition can be made immediately without delay. 1, 2, 3

Rationale for No Washout Period

When transitioning between medications for heart failure management, the washout requirements differ based on the medication class:

• ARB to ARNI transition: No washout period required
• ACEi to ARNI transition: Strict 36-hour washout period required

Losartan is an angiotensin II receptor blocker (ARB), while Entresto (sacubitril/valsartan) is an angiotensin receptor-neprilysin inhibitor (ARNI) that contains valsartan (an ARB component). The 2021 ACC Expert Consensus specifically states: "When making the transition from an ACEI to an ARNI, a 36-hour washout period should be strictly observed to avoid angioedema, a delay that is not required when switching from an ARB to an ARNI." 1

Dosing Considerations

While no washout period is needed, the initial dose of Entresto should be selected based on the patient's current losartan dose:

• For patients on high-dose ARB (losartan 100 mg daily): Start Entresto at 49/51 mg twice daily
• For patients on low/medium-dose ARB (losartan 25-50 mg daily): Start Entresto at 24/26 mg twice daily 1, 2

The target dose of Entresto is 97/103 mg twice daily, which should be achieved by doubling the dose every 2-4 weeks as tolerated 3.

Special Precautions

Although no washout is required, be aware of these important considerations:

• Contraindications to Entresto:

  • History of angioedema with ACEi or ARB therapy
  • Pregnancy (fetal toxicity)
  • Severe hepatic impairment (Child-Pugh C)
  • Concomitant use of ACEi 1, 2, 3

• Dose adjustments needed for:

  • Severe renal impairment (eGFR <30 mL/min/1.73 m²)
  • Moderate hepatic impairment (Child-Pugh B)
  • Elderly patients (≥75 years)
  • Systolic blood pressure <100 mmHg 1, 2

Monitoring Recommendations

After initiating Entresto:

• Check blood pressure, renal function, and potassium levels within 1-2 weeks
• More frequent monitoring for elderly patients or those with renal impairment
• Watch for hypotension, especially in volume-depleted patients 2

Common Pitfalls to Avoid

1. Don't confuse ARB-to-ARNI with ACEi-to-ARNI transitions: The 36-hour washout applies only when switching from ACEi medications, not ARBs like losartan 1

2. Don't overlook baseline assessment: Before initiating Entresto, assess blood pressure, renal function, and potassium levels to ensure appropriate dosing 2

3. Don't miss dose adjustments: Starting at too high a dose in vulnerable patients can lead to hypotension; follow the recommended starting doses based on previous ARB dosing 1, 2

4. Don't forget about drug interactions: Concomitant use of aliskiren in diabetic patients is contraindicated 2

The evidence strongly supports direct transition from losartan to Entresto without a washout period, with appropriate dose selection based on the patient's current losartan dose and clinical status.