What drugs should not be taken with Entresto?

In this article:

• How Entresto works
• Entresto drug interactions
• Other Entresto interactions
• How to minimize the risk of Entresto interactions

In this article

• How Entresto works
• Entresto drug interactions
• Other Entresto interactions
• How to minimize the risk of Entresto interactions

Entresto (sacubitril-valsartan) is a brand-name prescription medication that contains a combination of drugs, sacubitril and valsartan. It’s approved by the Food and Drug Administration (FDA) to treat heart failure. It’s used to reduce the risk of death due to heart disease (cardiovascular death) and hospitalization for heart failure. Though it can be used in both adults and children older than 1, the drug carries some strict warnings about its safety in some people already taking other medications. Read on for what you should know about Entresto and its drug interactions.

RELATED: Entresto generic availability, cost, and dosage

How Entresto works

Entresto is a combination medicine of sacubitril, a neprilysin inhibitor, and valsartan, an angiotensin II receptor blocker (ARB). This combination makes Entresto the first drug of its class, called angiotensin receptor neprilysin inhibitors (ARNIs). 

Stephanie Nielsen, Pharm.D., practitioner at The DNA Company, explains how the drug works: “Sacubitril helps open up your blood vessels and remove excess fluid, making it easier for your heart to pump. Valsartan will relax your blood vessels and lower your blood pressure, reducing strain on your heart. Together, they help your heart move blood more efficiently, which helps you feel better and breathe easier.” 

Common side effects of Entresto include low blood pressure, which may manifest as dizziness, lightheadedness, or fatigue. The drug also increases potassium levels in the blood and can cause the development of a cough or kidney failure. 

Entresto is not for people who are pregnant, as it can interfere with fetal kidney function. This is a black box warning on the drug, meaning it’s a warning for very serious or life-threatening risks of the drug.

Lastly, Entresto is also cautioned in people who have kidney disease, as it can decrease kidney function. 

Entresto drug interactions

Entresto’s combination of drugs leads to some of its potential interactions with a few common classes of drugs. 

Angiotensin converting enzyme (ACE) inhibitors

ACE inhibitors are typically prescribed for treating high blood pressure, and work on a pathway called the renin-angiotensin-aldosterone system to regulate blood pressure. Examples of ACE inhibitors include lisinopril, quinapril, and Lotensin (benazepril). “ACE inhibitors such as lisinopril or enalapril are used to lower blood pressure, but taking them with Entresto can actually contribute to breathing problems or even swelling,” Dr. Nielsen says.

“Patients should know that Entresto cannot be used within 36 hours of an ACE inhibitor, which can increase the likelihood of swelling or drops in blood pressure,” says Blen Tesfu, MD, physician and medical adviser at Welzo. This reaction is called angioedema, and it can be life-threatening. 

Angiotensin II receptor blockers (ARBs)

It’s recommended not to use Entresto with another ARB drug since Entresto already has valsartan. Taking the two can increase the risk of side effects. Common side effects of ARBs include a stuffy nose, upper respiratory infections, cough, feeling dizzy, and low blood pressure. The most serious effects of combining the two medications include high potassium levels, very low blood pressure, and kidney damage.

Common ARBs include losartan (generic Cozaar), Diovan (valsartan), candesartan, and Avapro (irbesartan). 

Aliskiren

Aliskiren is the generic version of the brand-name drug Tekturna. Both are drugs prescribed to lower blood pressure in adults and children 6 years and older. People with Type 2 diabetes or kidney problems taking aliskiren should not take Entresto at the same time. 

Taking aliskiren and Entresto together can increase the risk of low blood pressure, high blood potassium, and decreased kidney function. 

Potassium-sparing diuretics

Potassium-sparing diuretics are medications most often prescribed for high blood pressure or heart failure. They’re a type of water pill that removes excess fluid from your body. As the name suggests, potassium-sparing diuretics keep potassium ions in the blood in exchange for eliminating sodium. “When combined with Entresto, they can actually cause irregular heartbeats by raising your potassium levels too high,” Nielsen says. 

High potassium in the blood is called hyperkalemia. There aren’t typically signs of early hyperkalemia, but at certain levels, hyperkalemia can feel like heart palpitations, muscle weakness, and tingling sensations. Seek medical attention if you’re taking Entresto and you feel any of these symptoms. If untreated, hyperkalemia can cause paralysis, heart attacks, or death. 

Examples of potassium-sparing diuretics include spironolactone, triamterene, and amiloride.

Nonsteroidal anti-inflammatory drugs (NSAIDs) 

Taking nonsteroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 (COX-2) inhibitor drugs with Entresto, can worsen kidney function. Older adults, people who are on diuretics, or who have poor kidney function, are especially at risk of this interaction. People taking these medications with Entresto may have their kidney function monitored by their healthcare providers. 

Common NSAIDs include Advil (ibuprofen) and Naprosyn (naproxen), often used for pain management. Celebrex (celecoxib) is a selective COX-2 inhibitor used for pain and headaches.

Lithium

Lithium may be prescribed for people with bipolar disorder. Healthcare providers prescribe and monitor lithium very carefully to ensure patients get a safe and effective dose of the drug to control and prevent manic episodes in people with bipolar disorder. Having lithium levels too high or too low could mean an increased risk of side effects or uncontrolled symptoms.

Entresto increases lithium concentrations in the blood. People taking Entresto with lithium have a risk of lithium toxicity, which could cause symptoms like tremors, difficulty walking, and altered consciousness. Healthcare providers may order regular blood tests to make sure you have safe lithium levels while taking Entresto.

Other Entresto interactions

How Entresto works can also affect someone’s lifestyle and diet. Because of valsartan’s tendency to increase potassium levels in the blood, patients taking Entresto should be most mindful of sources of potassium in their diet.

Look for excess potassium in potassium supplements, potassium-rich foods, and salt substitutes containing potassium salts. Potassium-rich foods include avocados, dried fruits, bananas, potatoes, beets, acorn squash, spinach and other greens, almonds, and coconut water. 

People taking Entresto should also exercise caution with drinking alcohol. “If you enjoy an afternoon drink to wind down, you might want to reconsider it for a while since alcohol and CBD can make you feel dizzy or confused, especially while your body is getting used to Entresto,” Dr. Nielsen says. Alcohol lowers blood pressure along with valsartan, so people mixing the two may experience certain symptoms of low blood pressure. Low blood pressure, or hypotension, can feel like dizziness, lightheadedness, heart palpitations, blurred vision, fatigue, nausea, or fainting. 

RELATED: Foods to avoid while taking Entresto

How to minimize the risk of Entresto interactions

You can lower the risk of Entresto interactions largely by speaking to your healthcare provider about your medical conditions and medication history before you start taking it. Be sure to share your full medication list, alcohol consumption habits, and your regular diet to be able to make a plan around changes or adjustments to your care.

When you start taking Entresto, it’s also important to follow up with your healthcare provider about any new or worsening symptoms to ensure you have the right dosage. If you’re not sure whether a symptom is due to starting a new drug, it’s best to check with your healthcare provider first. Dr. Tesfu recommends close monitoring by a medical professional to minimize risks and maximize the benefits of the drug.

Finally, contact the provider who prescribed Entresto to let them know about any new drugs you’re prescribed so they can check for interactions. “You should always talk with your healthcare provider or pharmacist before starting anything new,” Dr. Nielsen advises.

Bottom line

Since Entresto is a combination of two drugs, sacubitril and valsartan, it comes with the potential for interactions with either drug. Drug classes that interact with Entresto include ACE inhibitors, ARBs, potassium-sparing diuretics, NSAIDs, aliskiren, and lithium. Talk to your healthcare provider if you have concerns about Entresto interactions. They will be able to work with you to determine the cause of the issues and possibly recommend alternatives to Entresto.