What to Know About Entresto Side Effects

Entresto (Sacubitril/Valsartan) is one of the most effective medications for heart failure, shown to significantly reduce hospitalizations and cardiovascular death. But like all medications, it comes with potential side effects.

The good news: most side effects are mild and manageable, especially during the first few weeks as your body adjusts. The key is knowing what's normal, what's not, and when to call your doctor.

What Is Entresto?

Entresto is a combination medication that contains two active ingredients — Sacubitril and Valsartan. It belongs to a drug class called angiotensin receptor-neprilysin inhibitors (ARNIs). It's FDA-approved to treat heart failure in adults and children aged 1 year and older, and it works by reducing strain on the heart while helping the body eliminate excess fluid and sodium.

For a more detailed overview, see our guide on what Entresto is, its uses, and dosage.

Common Side Effects

These are the side effects reported most frequently in clinical trials. They're generally mild to moderate and often improve as your body adjusts to the medication over the first few weeks.

• Low blood pressure (hypotension) — This is the most common side effect. You may feel lightheaded, dizzy, or faint, especially when standing up quickly. It's more likely during the first few weeks or after a dose increase.
• High potassium (hyperkalemia) — Entresto can raise potassium levels in your blood. Your doctor will monitor this with regular blood tests. You may not feel symptoms, which is why lab monitoring is important.
• Cough — A dry, persistent cough can occur. It's usually milder than the cough associated with ACE inhibitors like Lisinopril.
• Dizziness — Often related to low blood pressure. It tends to happen when you change positions (like going from sitting to standing).
• Fatigue — Some patients feel more tired than usual, especially early in treatment. This often improves over time.
• Nausea — Mild stomach upset can occur. Taking Entresto with food may help.
• Diarrhea — Usually mild and temporary.
• Kidney function changes — Mild increases in creatinine levels are possible. Your doctor will track this with blood work.

Serious Side Effects

These are less common but require immediate medical attention. If you experience any of the following, call your doctor right away or go to the emergency room.

Angioedema

This is swelling of the face, lips, tongue, or throat that can make it hard to breathe or swallow. It's a medical emergency. Angioedema is more likely if you've had it before with an ACE inhibitor or ARB. If you experience sudden swelling in your face or throat, call 911 immediately.

Severe Low Blood Pressure

While mild dizziness is common, severe hypotension — where you feel like you might pass out, have blurred vision, or feel extremely weak — needs medical attention. This is more likely if you're dehydrated, taking other blood pressure medications, or have kidney problems.

Acute Kidney Failure

Signs include a significant decrease in how much you urinate, swelling in your legs or ankles, shortness of breath, or confusion. This is more likely in patients who already have kidney impairment.

Severe Hyperkalemia

Dangerously high potassium levels can cause muscle weakness, an irregular heartbeat, or even cardiac arrest. Your doctor monitors potassium through regular blood tests, but if you notice heart palpitations, muscle weakness, or numbness/tingling, contact your doctor right away.

Fetal Toxicity (Boxed Warning)

Entresto carries an FDA boxed warning — the most serious type — about the risk of harm to an unborn baby. If you become pregnant while taking Entresto, stop the medication and contact your doctor immediately. Drugs that act on the renin-angiotensin system can cause injury and death to a developing fetus.

Who May Be at Higher Risk for Side Effects?

Certain groups of patients may experience side effects more frequently or more severely:

• Pregnant women — Entresto is contraindicated in pregnancy due to fetal toxicity risk.
• Patients with kidney impairment — Higher risk of hyperkalemia and worsening kidney function. The starting dose is typically lower (24/26 mg twice daily) for severe renal impairment.
• Patients with liver disease — Moderate hepatic impairment requires a lower starting dose. Entresto should be avoided entirely in severe liver disease (Child-Pugh C).
• Elderly patients — While no dose adjustment is required, older adults should be monitored more closely for low blood pressure and kidney changes.
• Patients switching from an ACE inhibitor — The risk of angioedema is highest during the transition. A mandatory 36-hour washout period between stopping an ACE inhibitor and starting Entresto helps reduce this risk.
• Nursing mothers — Entresto is not recommended during breastfeeding due to potential risk to the infant.

How to Manage Common Side Effects

Most side effects can be managed with simple strategies:

For Low Blood Pressure and Dizziness

• Stand up slowly from sitting or lying down.
• Stay well hydrated — drink plenty of water throughout the day.
• Avoid alcohol, which can lower blood pressure further.
• Tell your doctor if you're also taking other blood pressure medications — the combination may need adjustment.

For Cough

• If you switched from an ACE inhibitor, the cough may actually improve on Entresto since it tends to be milder.
• Stay hydrated and use throat lozenges if needed.
• If the cough is bothersome, talk to your doctor — don't stop the medication on your own.

For High Potassium

• Avoid potassium supplements unless your doctor specifically prescribes them.
• Limit high-potassium foods (bananas, oranges, potatoes, tomatoes) if your levels are elevated.
• Don't use salt substitutes — many contain potassium chloride.
• Keep all lab appointments so your doctor can monitor your levels.

For Nausea and Diarrhea

• Take Entresto with food if stomach upset is an issue.
• These symptoms usually resolve within the first few weeks.

For Fatigue

• Give your body time to adjust — fatigue often improves after the first couple of weeks.
• Maintain a regular sleep schedule and light exercise as tolerated.
• If fatigue is severe or persistent, let your doctor know.

Final Thoughts

Entresto is a proven, life-saving medication for heart failure, and most people tolerate it well. The side effects — particularly low blood pressure and dizziness — are most common during the first few weeks and often improve as your body adjusts. The most important things you can do are: keep your follow-up appointments, get your blood work done on schedule, and know the warning signs that require immediate attention.

If you're worried about side effects, talk to your doctor before stopping the medication. Stopping Entresto suddenly can worsen heart failure. Your doctor can adjust your dose, change the timing, or address the specific issue you're experiencing.

For more about Entresto, including how it works, drug interactions to watch for, and ways to save money on your prescription, explore our other guides.