Ibuprofen, Spironolactone, and More: 9 ACE Inhibitor Interactions to Be Aware of

Angiotensin-converting enzyme (ACE) inhibitors are a popular group of blood pressure medications. They can also be used to treat heart failure and protect your kidneys. Common ACE inhibitors include lisinopril (Zestril, Qbrelis) and ramipril.

Whether you’re just starting an ACE inhibitor or have been on one for a while, staying safe while taking it is key. One thing to keep in mind is drug interactions. There are several medications, supplements, and foods that can raise your risk of side effects or complications. So what ACE inhibitor interactions should you know about?

ACE inhibitor interactions

The following medications, supplements, and foods interact with ACE inhibitors:

• Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil, Motrin)

• Angiotensin II receptor blockers (ARBs), such as losartan (Cozaar)

• Diuretics (water pills), such as spironolactone (Aldactone)

• Kerendia (finerenone)

• Entresto (sacubitril / valsartan)

• Aliskiren (Tekturna)

• Lithium (Lithobid)

• Other medications that raise potassium levels, such as sulfamethoxazole / trimethoprim (Bactrim, Septra)

• Potassium supplements

• Potassium-rich foods

• Some salt substitutes

This isn’t a complete list. So be sure to discuss all the medications you take with your healthcare team before starting an ACE inhibitor. Below, we’ll dig deeper into what you should know about nine common ACE inhibitor interactions.

1. NSAIDs

ACE inhibitors interact with NSAIDs. This group of pain relievers has both over-the-counter (OTC) and prescription-only options. Common NSAIDs include:

• Ibuprofen

• Naproxen (Aleve, Naprosyn)

• Meloxicam

• Celecoxib (Celebrex, Elyxyb)

Taking an ACE inhibitor with NSAIDs can raise the risk of kidney damage. What’s more, these pain relievers can raise blood pressure. So your ACE inhibitor may not work as well if you’re also taking NSAIDs.

Regular use of NSAIDs can increase your risk of a heart attack. And if you’ve recently had a heart attack, taking NSAIDs can raise your risk of serious bleeding or another heart attack.

Occasional use of these pain relievers may be OK for some people taking ACE inhibitors. But double-check with your healthcare team first. There are many people who shouldn’t take NSAIDs.

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One possible NSAID alternative is acetaminophen (Tylenol). This OTC pain reliever doesn’t impact the kidneys, nor does it interact with ACE inhibitors.

Good to know: Aspirin is also an NSAID. But it works differently from others in its class. Some people take a daily low-dose aspirin for heart protection. So it’s possible you may take both an ACE inhibitor and aspirin. But daily aspirin isn’t right for everyone. Don’t start taking it without your healthcare team’s OK.

2. ARBs

ACE inhibitors also interact with ARBs, another group of blood pressure medications. ACE inhibitors and ARBs work similarly and have similar side effects.

Examples of ARBs include:

• Losartan

• Valsartan (Diovan)

• Olmesartan (Benicar)

Combining ACE inhibitors and ARBs raises the risk of side effects. These include high potassium levels (hyperkalemia) and kidney damage. And it’s unlikely that you’d get much more benefit from taking them both than from taking just one of them.

It’s recommended to avoid taking an ARB if you’re taking an ACE inhibitor. There are other blood pressure medication combinations that are safer, if needed.

3. Water pills

ACE inhibitors interact with water pills, as well. Despite this interaction, it’s common to take both. That’s because the benefits typically outweigh the risks. In fact, there are several combination blood pressure pills that contain both an ACE inhibitor and a water pill.

There are different types of water pills available, including:

• Thiazide diuretics, such as hydrochlorothiazide (Microzide)

• Thiazide-like diuretics, such as chlorthalidone (Thalitone)

• Loop diuretics, such as furosemide (Lasix)

• Potassium-sparing diuretics, such as triamterene (Dyrenium)

• Aldosterone antagonists, such as spironolactone

Taking water pills with an ACE inhibitor can put extra strain on your kidneys. In some cases, this could lead to kidney damage. Your blood pressure could also drop too low.

Potassium-sparing diuretics and aldosterone antagonists can raise your potassium levels. Combining one of them with an ACE inhibitor can lead to high potassium levels. In rare cases, high potassium can cause abnormal heart rhythms.

If you’re taking both medications, your prescriber should order blood tests from time to time. These tests will help them monitor your kidney function and potassium levels. If they notice that either moves into an unhealthy range, they may make dosage adjustments to one or more medications.

4. Kerendia

ACE inhibitors also interact with Kerendia. This is a medication used to treat chronic kidney disease (CKD) in people with Type 2 diabetes and certain types of heart failure. Combining an ACE inhibitor and Kerendia could lead to high potassium levels.

It’s possible you may take both of these medications. If you do take an ACE inhibitor and Kerendia, your prescriber should order routine blood tests to make sure your potassium levels are at an ideal range. Be sure to go for these tests on time.

5. Entresto

It’s contraindicated to take an ACE inhibitor with the heart failure medication Entresto. This means you should avoid it, because the risks greatly outweigh the benefits for most people. This ACE inhibitor interaction is twofold.

Entresto contains valsartan (an ARB). As mentioned, you shouldn’t take an ACE inhibitor and an ARB together. It raises the risk of kidney damage and high potassium levels.

Entresto also contains sacubitril. Taking sacubitril with an ACE inhibitor raises your risk for angioedema. This is when you have swelling of deep tissues in your body. Angioedema commonly causes swelling to the lips, tongue, and throat. It can be life-threatening.

If you’re switching from an ACE inhibitor to Entreso, you should separate them by at least 36 hours (1.5 days).

6. Aliskiren

Avoid combining an ACE inhibitor with the blood pressure medication aliskiren, especially if you have diabetes. This combination can cause kidney damage, low blood pressure, and high potassium levels. People living with diabetes have a greater risk of these complications.

It’s unlikely that you’d benefit from taking both an ACE inhibitor and aliskiren. Talk to your prescriber about safer blood pressure medication combinations.

7. Lithium

ACE inhibitors also interact with lithium, a mood stabilizer. Your kidneys help remove lithium from your body. So if you take other medications that impact the kidneys, they may interact with lithium.

ACE inhibitors can cause lithium to remain in your body longer than it should and at higher levels. And this can cause lithium toxicity (high lithium levels). This side effect can be life-threatening. Symptoms include tremors, dizziness, and blurry vision. Seek medical help right away if you think you’re experiencing lithium toxicity.

If you take both an ACE inhibitor and lithium, you may need to go for more frequent blood tests. These help make sure your lithium levels are at an ideal range. If your levels get too high, your prescriber may lower your lithium dosage.

8. Other medications that raise potassium levels

There are more medications that raise potassium levels than those discussed above. Some examples include:

• Sulfamethoxazole / trimethoprim

• Beta blockers, such as metoprolol (Lopressor, Toprol XL)

• Some immunosuppressants, such as tacrolimus (Prograf)

This isn’t a full list. Your pharmacist can let you know if any medications you take raise potassium levels.

Taking an ACE inhibitor with other medications that raise potassium could cause your potassium levels to get too high. If you need to combine them, your prescriber will likely order regular blood tests to monitor your potassium levels.

9. Foods and supplements that raise potassium levels

There are also several foods and dietary supplements that raise potassium levels. And that means they interact with ACE inhibitors.

Some common examples of potassium-rich foods include:

• Avocado

• Banana

• Dried apricot

• Lentils

• Acorn squash

• Raisins

• Baked potato

• Kidney beans

• Sweet potato

• Mango

• Cucumber

• Salmon

Examples of supplements that raise potassium levels include:

• Potassium supplements, such as potassium chloride (Klor-Con)

• Electrolyte supplements (for hydration)

• Some salt substitutes

• Alfalfa

• Nettle

• Dandelion

• Milkweed

• Siberian ginseng

• Hawthorn berry

• Noni juice

• Horsetail

Talk to your healthcare team about your dietary potassium, especially if you’re living with CKD. They can let you know if you should make changes to your diet or supplements.

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Written by:

Aileen Chu, PharmD, BCPS

Aileen Chu, PharmD, has over 8 years of experience working as a clinical pharmacist in the emergency department. Chu is also a pharmacotherapeutics instructor at Point Loma Nazarene University.

Edited by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

Reviewed by:

Stacia Woodcock, PharmD

Stacia Woodcock, PharmD, is a pharmacy editor for GoodRx. She earned her Doctor of Pharmacy degree from the University of Kentucky and is licensed in New York and Massachusetts.

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