6 Entresto Interactions You Should Know About

When Entresto was FDA approved in 2015, it changed the way heart failure was treated. It’s a unique combination of two medications: sacubitril and valsartan. Now, Entresto is a first-choice medication for treating heart failure.

Like all medications, Entresto has possible side effects and drug interactions. Here, we’ll cover six of the most important Entresto interactions you should know about.

1. ACE Inhibitors like lisinopril

You shouldn’t take Entresto with angiotensin-converting enzyme (ACE) inhibitors. Examples of ACE inhibitors include:

• Lisinopril (Zestril)

• Enalapril (Vasotec)

• Benazepril (Lotensin)

• Quinapril (Accupril)

• Ramipril (Altace)

• Captopril

• Fosinopril

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The reason for this interaction is the sacubitril ingredient in Entresto. Taking sacubitril and an ACE inhibitor increases your risk of angioedema. This is a swelling of the deep tissues in the body. This commonly includes the tongue, throat, lips. It can also happen in the face and neck. If the swelling is severe, it can cause your airways to close up and make it difficult to breathe. If you have trouble breathing, it requires emergency medical treatment. This is why it’s best to avoid taking Entresto with ACE inhibitors.

Good to know: ACE inhibitors are commonly used to treat many conditions. This includes heart failure and high blood pressure. If you take an ACE inhibitor and your healthcare provider recommends Entresto for heart failure, you’ll have to stop your ACE inhibitor. You should wait at least 36 hours after your last dose of the ACE inhibitor to start Entresto. Follow your provider’s instructions for exactly how to make this switch.

2. Other angiotensin-receptor blockers (ARBs) like losartan

Entresto shouldn’t be taken with angiotensin II receptor blockers (ARBs). This is because Entresto contains an ARB called valsartan. Taking Entresto with other ARBs can increase the risk of side effects like dizziness, headaches, and tiredness. More seriously it can lead to severely low blood pressure (hypotension), high potassium levels, and kidney problems.

Examples of ARBs include:

• Losartan (Cozaar)

• Olmesartan (Benicar)

• Telmisartan (Micardis)

• Valsartan (Diovan)

• Irbesartan (Avapro)

• Candesartan (Atacand)

• Azilsartan (Edarbi)

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Like ACE inhibitors, ARBs treat many conditions including high blood pressure and heart failure. So if you’re taking an ARB and your healthcare provider recommends Entresto, you’ll have to stop taking your ARB. Don’t make the switch without specific instructions from your provider about how to do so.

3. Aliskiren

Aliskiren (Tekturna) is used to treat high blood pressure in adults and some children. People with diabetes or kidney problems shouldn’t take aliskiren and Entresto together. This is due to the valsartan ingredient in Entresto. Taking valsartan (or any ARB) and aliskiren together can increase the risk for kidney problems, low blood pressure, and high potassium levels.

If you have diabetes or kidney problems and you take aliskiren, let your healthcare provider know before starting Entresto. Your provider will also check how well your kidneys work during treatment with Entresto. If your kidney function declines during treatment, and you take aliskiren, they’ll likely make a change to your medication regimen.

4. Medications that increase potassium

Entresto can increase the amount of potassium in your blood. So it can interact with other medications and substances that have the same effect. Examples include:

• Aldosterone antagonists, like spironolactone (Aldactone)

• Potassium-sparing diuretics like triamterene

• Potassium supplements

Keep in mind that many over-the-counter (OTC) supplements and multivitamins contain potassium. And even a diet high in potassium can increase your risk of too high potassium levels in the blood. Before and during treatment with Entresto, your healthcare provider will likely check your potassium levels. If they’re too high, they may make changes to your medication regimen. If you experience symptoms of high potassium — such as tiredness, muscle weakness, and a numbness or tingling sensation — let your healthcare provider know.

5. NSAIDs like ibuprofen

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn), and celecoxib (Celebrex), are widely used to treat inflammation and pain. Some NSAIDs are only available with a prescription (like celecoxib), but most are available OTC.

Taking Entresto and an NSAID at the same time increases your risk for kidney problems. This interaction can lead to acute kidney damage, although this is rare. Symptoms include peeing very little or not at all, feeling weak or tired, and having swelling in your ankles and feet. If you experience kidney problems due to this interaction, your healthcare provider will likely recommend stopping your NSAID or Entresto (or both).

Before and during treatment with Entresto, your provider will monitor your kidney function with blood tests. If your kidneys aren’t working as well as expected, they may start you at a lower dose of Entresto.

Keep in mind: NSAIDs are in many OTC products, including cough and cold medications. For example, ibuprofen is in several OTC products, such as Advil PM (ibuprofen / diphenhydramine) and Advil Sinus Congestion & Pain (ibuprofen / phenylephrine). Taking too many NSAIDs can be dangerous and increase your risk of an interaction with Entresto. Avoid this risk by giving your provider and pharmacist a list of all the prescription and OTC medications you take. They can help you check if you take multiple NSAID products.

6. Lithium

Lithium (Lithobid) is a mood stabilizer that treats bipolar disorder. If you take Entresto and lithium, Entresto may increase lithium levels in your blood.

If you have heart failure and bipolar disorder, it’s possible that you’ll need Entresto and lithium to effectively treat your conditions. Your healthcare provider will closely monitor the level of lithium in your blood if this is the case. In fact, you’ll need to have your lithium levels monitored even if lithium is the only medication you take.

Lithium works well to treat bipolar disorder. But even slightly increased lithium levels can raise your risk for lithium side effects. So if you take lithium and Entresto, it’s a good idea to watch for symptoms of lithium toxicity. Examples include:

• Problems with balance, coordination, or speech

• Tremors

• Blurry vision

• Kidney failure

• Seizures

When should you contact your healthcare provider about a lithium interaction?

Talk to your healthcare provider about Entresto interactions before you start taking it. Give your provider and pharmacist a list of all your current medications. You should include all prescription and OTC medications and supplements you take. This way, your provider and pharmacist can review for possible Entresto interactions.

Sometimes, you should avoid a potential interaction entirely. For example, you should avoid taking ACE inhibitors and ARBs with Entresto. In other cases, your provider may just monitor the possible interaction closely.

If you develop side effects when taking Entresto, it could be due to a drug interaction. This includes peeing less, feeling extremely tired, or having blurry vision. Contact your healthcare provider if you develop any side effects. If any of your symptoms feel severe or life threatening, call 911 or go to the closest emergency room.

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Written by:

Alex Brewer, PharmD, MBA

Alex Brewer, PharmD, MBA, is a licensed pharmacist specializing in chronic disease and health and wellness. Upon completing his residency, he worked in the managed care field, conducting medication therapy management and adherence counseling sessions with Medicaid, Medicare, and private insurance patients, before transitioning to a career in medical writing.

Edited by:

Amy B. Gragnolati, PharmD, BCPS

Amy Gragnolati, PharmD, BCPS, is a pharmacy editor for GoodRx. Amy currently holds her pharmacist license in Georgia and California.

Reviewed by:

Austin Ulrich, PharmD, BCACP

Austin Ulrich, PharmD, BCACP, is a board-certified ambulatory care clinical pharmacist. In his early career, he provided direct patient care in a variety of settings, including hospital and community pharmacies, and in a primary care clinic as a clinical pharmacist.

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