Entresto Dosing and Titration
The standard starting dose of Entresto for adults with heart failure is 49/51 mg twice daily, with titration to the target dose of 97/103 mg twice daily after 2-4 weeks, as tolerated. 1
Standard Adult Dosing
- Starting dose: 49/51 mg (sacubitril 49 mg/valsartan 51 mg) twice daily
- Target dose: 97/103 mg twice daily
- Titration schedule: Double the dose after 2-4 weeks to reach target 1
- Monitoring: Check blood pressure, electrolytes, and renal function after initiation and during titration 2
Dose Adjustments for Specific Populations
ACE Inhibitor/ARB-Naïve or Low-Dose Patients
Start at 24/26 mg twice daily if the patient is:
- Not currently taking an ACE inhibitor or ARB
- Previously on low-dose ACE inhibitor (equivalent to <10 mg enalapril daily)
- Previously on low-dose ARB (equivalent to <160 mg valsartan daily)
Then increase every 2-4 weeks following standard titration 2, 1
High-Dose ACE Inhibitor/ARB Patients
Start at 49/51 mg twice daily if the patient is on:
- High-dose ACE inhibitor (equivalent to ≥10 mg enalapril daily)
- High-dose ARB (equivalent to ≥160 mg valsartan daily)
Severe Renal Impairment (eGFR <30 mL/min/1.73 m²)
Start at 24/26 mg twice daily, then double the dose every 2-4 weeks to target of 97/103 mg twice daily as tolerated 2, 1
No dose adjustment needed for mild-to-moderate renal impairment (eGFR 30-59 mL/min/1.73 m²) 2
Moderate Hepatic Impairment (Child-Pugh B)
Start at 24/26 mg twice daily, then double the dose every 2-4 weeks to target of 97/103 mg twice daily as tolerated 2, 1
No adjustment needed for mild hepatic impairment (Child-Pugh A). Avoid in severe hepatic impairment (Child-Pugh C) 2
Low Systolic Blood Pressure (<100 mmHg)
Start at 24/26 mg twice daily and titrate cautiously. Evidence shows that patients with systolic blood pressure 100-110 mmHg can achieve target dose in approximately 73% of cases, particularly with gradual (6-week) titration 3. Ensure patients are not volume-depleted before initiation to minimize hypotension risk 2.
Elderly Patients (≥75 years)
Start at 24/26 mg twice daily 2
Critical Timing Considerations
When switching from an ACE inhibitor: Observe a mandatory 36-hour washout period to avoid angioedema 2, 1
When switching from an ARB: No washout period required; can switch immediately 2
Titration Strategy
The evidence supports that gradual titration (6 weeks) maximizes achievement of target dose compared to rapid titration (3 weeks), particularly in patients previously on low-dose ACE inhibitors/ARBs 4. Both approaches are tolerable, but the conservative approach achieved target dose in 84.3% versus 77.8% with condensed titration 4.
Practical titration schedule:
- Assess tolerability at 2 weeks
- If tolerated, increase to next dose level
- Continue every 2-4 weeks until target dose of 97/103 mg twice daily is reached
- Monitor blood pressure, potassium, and creatinine at each step 2
Common Pitfalls to Avoid
- Do not delay initiation waiting for aldosterone antagonist therapy—this is not required before starting Entresto 2
- Do not underdose: Only 19% of patients in real-world practice reach target dose 5, yet higher doses are associated with significantly fewer hospitalizations and lower costs 5
- Do not stop for mild hypotension: Patients with systolic blood pressure as low as 100 mmHg can successfully reach target dose with gradual titration 3
- Do not forget the washout: The 36-hour ACE inhibitor washout is mandatory to prevent angioedema 1
Monitoring Parameters
After initiation and with each dose increase, monitor:
- Blood pressure (watch for symptomatic hypotension)
- Serum potassium (hold if >5.5 mmol/L until managed)
- Serum creatinine (acceptable if increase <30% within 4 weeks)
- Signs of angioedema (discontinue immediately if occurs)