Recommended Dosing of Entresto (Sacubitril/Valsartan) for Heart Failure
The recommended dosing of Entresto (sacubitril/valsartan) for heart failure with reduced ejection fraction is to start at 49/51 mg twice daily and titrate to the target dose of 97/103 mg twice daily after 2-4 weeks as tolerated by the patient. 1
Initial Dosing and Titration
- Starting dose: 49/51 mg twice daily (sacubitril 49 mg/valsartan 51 mg)
- Target dose: 97/103 mg twice daily (sacubitril 97 mg/valsartan 103 mg)
- Titration schedule: Double the dose after 2-4 weeks if the initial dose is tolerated 1
Special Considerations for Dosing
Severe Renal Impairment
- For patients with severe renal impairment (eGFR <30 mL/min/1.73 m²):
Low Blood Pressure
- For patients with low blood pressure:
- Consider a more conservative titration approach
- The "conservative" regimen (50 mg twice daily for 2 weeks, then 100 mg twice daily for 3 weeks, then 200 mg twice daily) may maximize attainment of target dose, particularly in patients previously on low-dose ACE inhibitors/ARBs 3
Important Administration Requirements
- ACE Inhibitor Washout: A mandatory 36-hour washout period is required when switching from an ACE inhibitor to Entresto 1
- Concomitant Medications: Entresto is contraindicated with concomitant use of ACE inhibitors 1
Efficacy and Tolerability
- Approximately 76% of patients can achieve and maintain the target dose of 97/103 mg twice daily without dose interruption or down-titration over 12 weeks 3
- The most common tolerability issues include:
- Hypotension (8.9% with condensed titration vs 5.2% with conservative titration)
- Renal dysfunction (7.3% with condensed vs 7.6% with conservative)
- Hyperkalemia (7.7% with condensed vs 4.4% with conservative) 3
Monitoring Recommendations
- Monitor blood pressure, renal function, and serum potassium regularly during initiation and titration
- Assess for signs of hypotension, particularly in patients with:
- Lower mean arterial pressure
- Lower serum chloride
- Presence of implantable cardiac devices
- Moderate or greater mitral regurgitation 4
Comprehensive Heart Failure Management
Entresto should be part of a comprehensive heart failure management approach that includes:
- Beta-blockers (after stabilization for patients with LVEF <40%)
- Mineralocorticoid receptor antagonists (for patients with LVEF <40% without severe renal failure or hyperkalemia)
- SGLT2 inhibitors (dapagliflozin or empagliflozin)
- Diuretics for symptom management 5
Entresto has been shown to reduce mortality and heart failure hospitalizations regardless of heart failure duration, with consistent improvements in cardiac biomarkers, health status, and cardiac remodeling 6.