ENTRESTO

What it is

Entresto contains sacubitril and valsartan as film-coated tablets. Three strengths are available: 24/26 mg, 49/51 mg, and 97/103 mg. Entresto is an angiotensin receptor neprilysin inhibitor (ARNI) that simultaneously inhibits neprilysin via sacubitrilat (the active metabolite of sacubitril) and blocks the angiotensin II type-1 (AT1) receptor via valsartan.

Approved indications

— Chronic heart failure (NYHA Class II–IV) with reduced ejection fraction in adult patients.

Dosing overview

The recommended starting dose is one tablet of 49 mg/51 mg twice daily. The dose should be doubled after 2 to 4 weeks to the target maintenance dose of one tablet of 97 mg/103 mg twice daily, as tolerated by the patient. A starting dose of 24 mg/26 mg twice daily is recommended for patients not currently taking an ACE inhibitor or an ARB, or patients previously taking low doses of these agents. A starting dose of 24 mg/26 mg twice daily should be considered for patients with risk factors for hypotension, including patients aged 75 years or older and patients with low systolic blood pressure (100–110 mmHg). Entresto may be administered with or without food.

Key safety warnings

Entresto must not be administered with an ACE inhibitor due to the risk of angioedema. Entresto must not be initiated until 36 hours after taking the last dose of ACE inhibitor therapy. Entresto lowers blood pressure and may cause symptomatic hypotension, especially in patients aged 75 years or older, patients with renal disease, and patients with low systolic blood pressure (<112 mmHg). Through its action on the renin-angiotensin-aldosterone system, hyperkalaemia may occur with Entresto. Serum potassium should be monitored periodically and treated appropriately, especially in patients with risk factors for hyperkalaemia such as severe renal impairment, diabetes, hypoaldosteronism, or a high potassium diet. Angioedema has been reported in 0.5% of patients treated with Entresto. If angioedema occurs, Entresto should be immediately discontinued and appropriate therapy and monitoring should be provided until complete and sustained resolution of signs and symptoms has occurred.

Contraindications

Entresto is contraindicated in patients with hypersensitivity to the active substances or excipients, concomitant use with ACE inhibitors, known history of angioedema related to previous ACE inhibitor or ARB therapy, hereditary or idiopathic angioedema, concomitant use with aliskiren in patients with Type 2 diabetes, severe hepatic impairment (biliary cirrhosis and cholestasis), and pregnancy.

PBS listing

Entresto is recommended for chronic heart failure with reduced left ventricular ejection fraction based on acceptable cost-effectiveness compared to enalapril.

Regulatory history

Entresto 24/26 mg, 49/51 mg, and 97/103 mg film-coated tablets were first listed on the ARTG on 20 January 2016. In November 2014, Entresto was not recommended by the PBAC for the treatment of chronic heart failure with reduced ejection fraction due to uncertain cost-effectiveness. In August 2016, the PBAC recommended Entresto for chronic heart failure with reduced left ventricular ejection fraction based on acceptable cost-effectiveness compared to enalapril, considering reduced price and a Risk Sharing Arrangement. In November 2024, the PBAC recommended an amendment to PBS listings to allow nurse practitioners to initiate treatment.