What is the recommended dosing regimen for Entresto (sacubitril/valsartan)?

From the Guidelines

The recommended starting dose of Entresto (sacubitril/valsartan) is 49 mg sacubitril and 51 mg valsartan twice daily, with a target dose of 97 mg sacubitril and 103 mg valsartan twice daily, as supported by the most recent guidelines 1. The dosing regimen for Entresto is crucial in managing heart failure with reduced ejection fraction (HFrEF).

• The initial dose is typically 49 mg sacubitril and 51 mg valsartan taken twice daily.
• This dose can be titrated up to the target maintenance dose of 97 mg sacubitril and 103 mg valsartan twice daily as tolerated by the patient.
• For patients who are naive to ACE inhibitors or ARBs, or those on low doses, a starting dose of 24 mg sacubitril and 26 mg valsartan twice daily is recommended, with gradual uptitration.
• It's essential to discontinue any ACE inhibitor at least 36 hours before initiating Entresto to avoid the risk of angioedema.
• Regular monitoring of blood pressure, renal function, and potassium levels is necessary during treatment with Entresto.
• The combination of sacubitril, a neprilysin inhibitor, and valsartan, an angiotensin receptor blocker, in Entresto provides a dual mechanism of action that benefits patients with HFrEF, as outlined in the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1. Key considerations in dosing Entresto include:
• Patient tolerance and ability to uptitrate to the target dose.
• Presence of severe renal impairment, which may require dose adjustments.
• Concomitant use of other medications that may interact with Entresto.
• Regular assessment of the patient's clinical status and adjustment of the treatment plan as needed. The most recent and highest quality study, the 2022 AHA/ACC/HFSA guideline 1, provides the basis for these recommendations, prioritizing morbidity, mortality, and quality of life outcomes in the management of HFrEF with Entresto.

From the Research

Dosing Regimen for Entresto (Sacubitril/Valsartan)

The recommended dosing regimen for Entresto (sacubitril/valsartan) is as follows:

• The initial dose is typically 24/26 mg twice daily, which can be increased to 49/51 mg twice daily after 2-4 weeks, and then to the target dose of 97/103 mg twice daily if tolerated 2.
• In patients with chronic kidney disease, the dose of sacubitril/valsartan can be increased to 97/103 mg twice daily, with monitoring of renal function and cardiac biomarkers 3.
• The dose of sacubitril/valsartan may need to be adjusted in patients with heart failure requiring hemodialysis, with a maximum combination dose of sacubitril (97 mg twice daily) and valsartan (103 mg twice daily) 4.

Key Considerations

• The dose of sacubitril/valsartan should be individualized based on patient tolerance and response to treatment 2, 3.
• Patients with chronic kidney disease should be monitored closely for changes in renal function and cardiac biomarkers when initiating or increasing the dose of sacubitril/valsartan 3, 5.
• The safety and efficacy of sacubitril/valsartan in patients with heart failure requiring hemodialysis have been demonstrated in clinical studies, with beneficial effects on all-cause mortality and all-cause hospitalization 4.