Sacubitril

Key facts

• Sacubitril is a neprilysin inhibitor. It is never prescribed alone: it is combined with the blood-pressure medicine valsartan in a single tablet, sold as Entresto, to treat chronic heart failure.
• You take it twice a day, with or without food, usually alongside other heart-failure medicines such as a beta-blocker.
• Sacubitril/valsartan can cause angioedema, a rapid swelling of the face, lips, tongue or throat that can block breathing. It must never be combined with an ACE inhibitor, and you must wait 36 hours after stopping an ACE inhibitor before starting it.
• Seek emergency care immediately for any swelling of the face, lips, tongue or throat, or difficulty breathing or swallowing.

What sacubitril treats

Sacubitril, combined with valsartan, treats chronic heart failure with reduced ejection fraction, where the heart's main pumping chamber does not squeeze as strongly as it should. It reduces the risk of hospitalization and death from heart failure and can ease symptoms such as breathlessness and fatigue over time.

How sacubitril works

Sacubitril blocks an enzyme called neprilysin, which normally breaks down natural hormones that widen blood vessels and help the kidneys remove excess sodium and fluid. Blocking neprilysin lets these protective hormones last longer, easing the strain on a weakened heart. Valsartan, the partner drug, blocks a different pathway that would otherwise narrow blood vessels and raise blood pressure. Together they reduce the workload on the heart.

Before you take it

• Do not take sacubitril/valsartan if you are pregnant. It can cause serious harm to a developing fetus, including kidney damage, so use effective contraception if pregnancy is possible.
• Never combine it with an ACE inhibitor. If switching from an ACE inhibitor, leave a gap of at least 36 hours between the last dose and the first dose of sacubitril/valsartan.
• Tell your prescriber if you have a history of angioedema, severe liver disease, severe kidney disease, or low blood pressure.
• Potassium supplements, salt substitutes, and some diuretics can raise potassium levels further; your levels will be checked regularly.

Side effects

Common effects include dizziness, low blood pressure, a mild cough, and tiredness.

Stop and seek urgent medical care for any of these:

• Swelling of the face, lips, tongue or throat, or sudden difficulty breathing or swallowing.
• Severe dizziness, fainting, or a very fast or irregular heartbeat.
• Little or no urine output, or worsening swelling in the legs and ankles.

Safety essentials

• Angioedema is the defining risk of this medicine. It can develop at any time during treatment and needs emergency care; people of African descent have a higher reported risk.
• Never take it with an ACE inhibitor, and observe the 36-hour washout in both directions when switching between the two drug classes.
• It is contraindicated in pregnancy. Blood pressure, kidney function and potassium levels are checked regularly during treatment.

This page is educational and does not replace advice from a doctor or pharmacist who knows your health history.