When should Entresto (sacubitril/valsartan) not be administered?

When Not to Administer Entresto (Sacubitril/Valsartan)

Entresto is contraindicated in patients with a history of angioedema related to previous ACE inhibitor or ARB therapy, during concomitant use of ACE inhibitors (must wait at least 36 hours between switching), in patients with hypersensitivity to any component, and with concomitant use of aliskiren in patients with diabetes. 1

Absolute Contraindications

• History of angioedema: Patients with any history of angioedema related to previous ACE inhibitor or ARB therapy should not receive Entresto due to increased risk of recurrent angioedema 2, 1

• Concomitant ACE inhibitor use: Do not administer Entresto within 36 hours of switching from or to an ACE inhibitor due to increased risk of angioedema 2, 1

• Hypersensitivity: Patients with known hypersensitivity to any component of Entresto should not receive the medication 1

• Aliskiren use in diabetes: Concomitant use of Entresto with aliskiren in patients with diabetes is contraindicated 1

• Pregnancy: Entresto can cause fetal harm when administered during pregnancy due to effects on the renin-angiotensin system 1

• Severe hepatic impairment: Use in patients with severe hepatic impairment (Child-Pugh C) is not recommended 1

Cautions and Relative Contraindications

• Hypotension: Use with caution in patients with systolic blood pressure <100 mmHg or in volume-depleted patients 2

• Renal impairment: Dose adjustment is required for severe renal impairment (eGFR <30 mL/min/1.73m²) 2, 1

• Moderate hepatic impairment: Start at half the recommended dose in patients with moderate hepatic impairment (Child-Pugh B) 1

• Hyperkalemia risk: Use with caution in patients with risk factors for hyperkalemia such as severe renal impairment, diabetes, or hypoaldosteronism 1

• Hereditary angioedema: Entresto should not be used in patients with hereditary angioedema 1

• Renal artery stenosis: Monitor renal function closely in patients with renal artery stenosis 1

Special Populations Requiring Caution

• Black patients: Entresto has been associated with a higher rate of angioedema in Black patients compared to non-Black patients 1

• Lactation: Limited data exists on use during lactation; consider risks and benefits 1

• Elderly: No specific contraindication, but monitor for hypotension and renal function changes 2

Monitoring Recommendations When Using Entresto

• Monitor blood pressure regularly, especially when initiating therapy or increasing doses 2

• Check renal function and electrolytes (particularly potassium) periodically 1

• Watch for signs of angioedema (swelling of face, lips, tongue, throat) which may require immediate discontinuation 1

• If hypotension occurs, consider dose adjustment of diuretics or temporarily reducing the Entresto dose 1

Clinical Pearls

• When switching from an ACE inhibitor to Entresto, a washout period of at least 36 hours is mandatory to reduce angioedema risk 2

• ARBs may be used as alternatives to ACE inhibitors and Entresto in patients with a history of angioedema 2

• For patients with severe renal impairment, start at half the usually recommended dose 1

• Angioedema associated with laryngeal edema can be fatal; ensure appropriate emergency measures are available 1