Entresto Removal by Hemodialysis
Entresto (sacubitril/valsartan) is NOT significantly removed by hemodialysis due to high protein binding of both components, and no dose adjustment or supplemental dosing is required after dialysis sessions. 1
Pharmacokinetic Properties Preventing Dialysis Removal
Both active components of Entresto exhibit characteristics that prevent effective removal by hemodialysis:
- Sacubitril, its active metabolite LBQ657, and valsartan are all highly protein-bound (94-97%), which prevents significant clearance through dialysis membranes 1
- The FDA label explicitly states: "ENTRESTO is unlikely to be removed by hemodialysis because of high protein binding" 1
- This high protein binding is the primary mechanism preventing dialysis removal, similar to other highly protein-bound medications 2
Dosing Recommendations for Dialysis Patients
The recommended starting dose for patients with severe renal impairment (eGFR <30 mL/min/1.73 m²) or those on hemodialysis is 24/26 mg twice daily 1
- No supplemental dosing is needed after hemodialysis sessions 1
- Dose titration should proceed cautiously based on blood pressure tolerance and clinical response 3
- Most dialysis patients in clinical studies received lower doses (only 14% ever reached the maximum 97/103 mg twice daily dose) 4
Clinical Evidence in Dialysis Populations
Recent real-world evidence demonstrates both efficacy and safety of Entresto in dialysis patients:
- A large Medicare study of 2,868 matched hemodialysis patients showed sacubitril/valsartan reduced all-cause mortality (HR 0.82) and all-cause hospitalization (HR 0.86) compared to ACE inhibitors/ARBs 4
- Hyperkalemia risk was actually lower with sacubitril/valsartan (HR 0.71) compared to traditional RAAS inhibitors 4
- Multiple smaller studies confirm improvements in cardiac function (LVEF increases of 7-9%), blood pressure control (SBP reductions of 10-16 mmHg), and heart failure symptoms in dialysis patients 5, 6, 7, 8
Safety Monitoring Considerations
While Entresto is not removed by dialysis, specific monitoring is warranted:
- Serum potassium should be monitored, though severe hyperkalemia rates remain low (approximately 4-5% at 6 months) and comparable to conventional therapy 9, 6
- Blood pressure monitoring is essential, as sacubitril/valsartan may cause more pronounced BP lowering than ACE inhibitors/ARBs, particularly in hemodialysis patients where SBP reductions of 11-16 mmHg are typical 7, 8
- Symptomatic hypotension occurs in approximately 8% of patients but rarely requires discontinuation 10
Common Pitfalls to Avoid
- Do not administer supplemental doses after dialysis sessions - the drug is not significantly removed and supplementation would risk toxicity 1
- Do not assume standard target doses are achievable - most dialysis patients require and tolerate lower maintenance doses than the general heart failure population 4
- Do not withhold therapy due to dialysis status alone - current evidence supports use in this population with appropriate dose adjustment and monitoring 11, 4, 7