From the Guidelines
The initial dose of Entresto (sacubitril/valsartan) for heart failure treatment is typically 49 mg sacubitril and 51 mg valsartan taken twice daily, but may be initiated at a lower dose of 24 mg sacubitril and 26 mg valsartan twice daily in certain patients. According to the most recent guidelines 1, for patients who haven't previously taken an ACE inhibitor or ARB, or those taking low doses of these medications, starting at this lower dose is recommended. Patients with severe renal impairment (eGFR <30 mL/min/1.73m²), moderate hepatic impairment, or elderly patients may also benefit from this lower starting dose. Before initiating Entresto, any ACE inhibitor should be discontinued at least 36 hours prior to avoid the risk of angioedema. Blood pressure, renal function, and potassium levels should be monitored regularly after starting treatment. The dose can be doubled every 2-4 weeks as tolerated to reach the target maintenance dose of 97 mg sacubitril and 103 mg valsartan twice daily. Entresto works by combining neprilysin inhibition (sacubitril) with angiotensin receptor blockade (valsartan), enhancing beneficial neurohormonal pathways while blocking harmful ones, ultimately improving cardiac function and reducing hospitalizations in heart failure patients. Key considerations for dosing are based on the latest clinical practice guidelines 1, which emphasize the importance of individualizing treatment based on patient characteristics and tolerance. While earlier guidelines 1 also supported the use of sacubitril/valsartan for heart failure, the most recent recommendations 1 provide the most up-to-date guidance on dosing and patient selection. In clinical practice, the choice of initial dose and subsequent titration should be guided by careful assessment of the patient's clinical status and potential for adverse effects.
From the FDA Drug Label
2.2 Adult Heart Failure The recommended starting dose of sacubitril and valsartan tablet is 49/51 mg orally twice-daily.
The initial dose of Entresto (sacubitril/valsartan) for the treatment of heart failure is 49/51 mg orally twice-daily 2.
From the Research
Initial Dose of Entresto
The initial dose of Entresto (sacubitril/valsartan) for the treatment of heart failure is not explicitly stated in the provided studies as a single, universally applicable dose. However, the studies offer insights into the dosing strategies and tolerability of sacubitril/valsartan in patients with heart failure.
- The study 3 mentions that the initiation/uptitration of sacubitril/valsartan starts from 50 mg twice daily, with the goal of reaching a target dose of 200 mg twice daily over either 3 or 6 weeks.
- Another study 4 discusses the use and tolerability of sacubitril/valsartan in a clinical practice setting, where the target dose is defined as 200 mg twice a day, but it notes that within 6 months, only 27.2% of patients achieved this target dose, with many starting at lower doses such as 50 mg or 100 mg twice a day due to various factors including side effects and patient compliance.
- The study 5 does not specifically address the initial dosing of sacubitril/valsartan but mentions a dose of 97/103 mg twice daily in the context of comparing its effects to irbesartan in patients with chronic kidney disease.
Key Points on Dosing
- Starting Dose: The starting dose often mentioned is 50 mg twice daily, which is then uptitrated.
- Target Dose: The target dose for many patients is 200 mg twice daily, but achieving this can depend on tolerability and individual patient factors.
- Uptitration: Uptitration strategies can vary, with some studies suggesting a more gradual approach may be beneficial for maximizing the attainment of the target dose, especially in certain patient groups.
Considerations
- The decision on the initial dose and uptitration strategy should be based on individual patient characteristics, including their ability to tolerate the medication, blood pressure, kidney function, and other factors.
- Clinical guidelines and the specific clinical context should guide the dosing of sacubitril/valsartan in heart failure patients.