What are the parameters for holding Entresto (sacubitril/valsartan)?

Parameters for Holding Entresto (Sacubitril/Valsartan)

Entresto should be held in patients with symptomatic hypotension (systolic blood pressure <100 mmHg), severe renal impairment (eGFR <30 mL/min/1.73 m²), or moderate to severe hepatic impairment (Child-Pugh B or C). 1, 2

Specific Parameters for Holding Entresto

Blood Pressure Parameters

• Symptomatic hypotension: Hold if patient has symptoms of hypotension with systolic BP <100 mmHg 1
• Volume depletion: Hold if patient is volume depleted as this increases risk of hypotension 1

Renal Function Parameters

• Severe renal impairment:
  • Traditional recommendation was to hold if eGFR <30 mL/min/1.73 m² 3, 2
  • However, recent evidence suggests continuation may be beneficial even with eGFR decline below this threshold 4
  • If continuing in severe renal impairment, use reduced dose (24/26 mg twice daily) 3, 2

Hepatic Function Parameters

• Moderate hepatic impairment (Child-Pugh B): Reduce dose to 24/26 mg twice daily 3, 2
• Severe hepatic impairment (Child-Pugh C): Hold medication as it is contraindicated 2

Electrolyte Abnormalities

• Hyperkalemia: Monitor closely, especially in patients with renal impairment
• Consider holding if potassium >5.5 mEq/L despite dose adjustment of other medications

Drug Interactions

• ACE inhibitor use: Must have 36-hour washout period between ACE inhibitor and Entresto to avoid angioedema 1, 2
• Aliskiren: Contraindicated in diabetic patients 2

Monitoring Recommendations

• Check blood pressure, renal function, and potassium levels within 1-2 weeks after starting or increasing the dose 3
• More frequent monitoring may be needed in patients with:
  • History of renal impairment
  • Elderly patients (≥75 years)
  • Concomitant use of other medications affecting renal function

Special Considerations

• Angioedema history: Entresto is contraindicated in patients with history of angioedema related to previous ACE inhibitor or ARB therapy 1, 2
• Pregnancy: Hold Entresto if pregnancy is detected due to fetal toxicity 2
• Hospitalization: Ensure patients are not volume-depleted before initiating or continuing Entresto during hospitalization for heart failure 1

Restarting After Holding

When restarting Entresto after holding:

• Consider starting at a lower dose (24/26 mg twice daily) if held for hypotension or worsening renal function
• Titrate dose gradually every 2-4 weeks as tolerated to target dose of 97/103 mg twice daily 1, 3
• Monitor blood pressure, renal function, and electrolytes closely after restarting

Remember that Entresto has demonstrated significant mortality and morbidity benefits in heart failure with reduced ejection fraction, so the goal should be to maintain patients on therapy when possible with appropriate dose adjustments rather than discontinuing completely 1, 5.