What is the maximum dose of Entresto (sacubitril/valsartan) for patients with impaired renal function (dialysis)?

Maximum Dose of Entresto in Dialysis Patients

For dialysis patients with severe renal impairment (eGFR <30 mL/min/1.73 m²), start Entresto at half the usual starting dose (24 mg/26 mg twice daily in adults), then titrate up to the maximum dose of 97 mg/103 mg twice daily as tolerated, following the standard dose escalation schedule. 1

Dosing Algorithm for Dialysis Patients

Initial Dosing

• Start at 24 mg/26 mg twice daily (half the standard starting dose) in adults with severe renal impairment including those on dialysis 1
• After initiation, increase the dose every 2-4 weeks following the recommended dose escalation: 24/26 mg → 49/51 mg → 97/103 mg twice daily 1
• The maximum target dose remains 97 mg/103 mg twice daily, identical to patients without renal impairment 1

Timing of Administration

• Administer doses after dialysis sessions to prevent premature drug removal and facilitate medication adherence monitoring 2, 3, 4
• This timing principle follows established practices for dialyzable medications in hemodialysis patients 2

Key Safety Considerations

Hyperkalemia Monitoring

• Mean serum potassium increases modestly (from 4.84 to 5.04-5.07 mmol/L) in anuric hemodialysis patients on sacubitril/valsartan 5
• Severe hyperkalemia (>6.0 mmol/L) occurred in only 2.8-4.2% of patients after 3-6 months of therapy, which was not statistically significant 5
• Monitor serum potassium levels regularly, particularly during dose titration 5

Hypotension Risk

• Sacubitril/valsartan has potent vasodilatory effects that may cause profound hypotension in dialysis patients 6
• Blood pressure decreases significantly during treatment, requiring careful monitoring 5
• Symptomatic hypotension is the most likely adverse effect and should be managed with supportive care 1

Dialyzability

• Sacubitril/valsartan is unlikely to be removed by hemodialysis due to high protein binding 1
• This characteristic supports once the patient is stabilized on therapy, the drug will maintain therapeutic levels between dialysis sessions 1

Contraindications in Dialysis Patients

• Do not use concomitantly with ACE inhibitors (require 36-hour washout period) 1
• Contraindicated with aliskiren in diabetic patients 1
• Avoid in patients with history of angioedema related to previous ACE inhibitor or ARB therapy 1

Practical Titration Strategy

Week 0-2: Start 24/26 mg twice daily (after dialysis on dialysis days) 1

Week 2-4: If tolerated, increase to 49/51 mg twice daily 1

Week 4+: If tolerated, increase to maximum dose of 97/103 mg twice daily 1

• Each dose increase should occur only if the patient tolerates the current dose without significant hypotension or hyperkalemia 1
• The standard 2-4 week titration interval applies to dialysis patients, though closer monitoring may be warranted 1