Entresto Side Effects: What to Expect and When to Call Your Doctor

Entresto (sacubitril/valsartan) is a powerful heart failure medication with a well-established safety profile from large clinical trials involving thousands of patients. Like all medications, it can cause side effects — and knowing what to watch for can help you respond quickly if something goes wrong. Here is what you need to know about Entresto side effects in 2026.

Boxed Warning: Fetal Toxicity

Entresto carries the FDA's most serious warning — a boxed warning — for fetal toxicity. Drugs that act on the renin-angiotensin system can cause injury or death to a developing fetus. If you become pregnant while taking Entresto, stop the medication as soon as possible and contact your doctor immediately. Use effective contraception while on Entresto. Breastfeeding is also not recommended during treatment.

Most Common Side Effects of Entresto

The most common side effects reported in clinical trials (PARADIGM-HF and PARAGON-HF) and post-marketing data:

Hypotension (low blood pressure): The most common side effect. You may feel dizzy, lightheaded, or weak — especially when standing up quickly. Your risk is higher if you also take diuretics (water pills) or start at a lower blood pressure. Your doctor may adjust your diuretic or Entresto dose if this becomes problematic.

Hyperkalemia (high potassium levels): Elevated potassium can disrupt heart rhythm and is more likely if you take potassium-sparing diuretics (spironolactone, amiloride), potassium supplements, or salt substitutes. Your doctor will monitor potassium with blood tests.

Cough: Less common with Entresto than with ACE inhibitors (which are notorious for causing a dry cough). However, a persistent cough can still occur with sacubitril/valsartan.

Dizziness: Often related to low blood pressure. Avoid sudden position changes (standing up too quickly) and report persistent dizziness to your doctor.

Renal impairment (kidney problems): Kidney function can decline with Entresto, particularly in patients with existing kidney disease or who are volume-depleted. Your doctor will monitor creatinine and BUN levels.

Serious Side Effects — Seek Medical Attention Immediately

Angioedema: Potentially life-threatening swelling of the face, lips, tongue, or throat. Seek emergency medical care immediately if you develop facial swelling or difficulty breathing. African Americans and people with a history of ACE inhibitor-related angioedema are at higher risk. Do not take Entresto if you have a history of angioedema from ACE inhibitors or ARBs.

Severe hypotension: If you feel faint, very weak, or actually lose consciousness, call 911 or go to the emergency room. Severe low blood pressure can be dangerous, especially in elderly or volume-depleted patients.

Acute kidney injury: Symptoms include markedly decreased urination, swelling, or fatigue. Contact your doctor right away if you notice signs of kidney problems.

Severe hyperkalemia: Muscle weakness, irregular heartbeat, or numbness can signal dangerously high potassium. This is a medical emergency.

Monitoring Schedule: What Your Doctor Will Check

When starting or adjusting sacubitril/valsartan, your doctor should monitor:

Blood pressure — at each visit and after dose changes

Serum potassium — baseline and periodically, especially at dose increases

Renal function (creatinine, BUN, eGFR) — baseline and periodically

Signs and symptoms of angioedema — at every visit

Who Is at Higher Risk for Side Effects?

Certain patients should be monitored more closely when starting Entresto:

Elderly patients (older age increases hypotension risk)

Patients already on diuretics (higher hypotension risk)

Patients with chronic kidney disease (higher renal impairment and hyperkalemia risk)

African Americans (higher angioedema risk)

Patients with prior angioedema from ACE inhibitors or ARBs (Entresto is contraindicated in this group)

When Should I Call My Doctor?

Call your doctor if you experience persistent dizziness, new or worsening cough, leg swelling, decreased urination, unusual weakness, or if you think you might be pregnant. Seek emergency care immediately for any facial swelling, throat tightness, or difficulty breathing. Also review Entresto drug interactions to avoid combinations that amplify side effect risk.