What medication should be avoided with ACE inhibitors?

October 10, 2025 •

5 min read

According to the National Institutes of Health, numerous medications can interact with ACE inhibitors, potentially causing life-threatening side effects. Understanding what medication should be avoided with ACE inhibitors is critical for preventing complications such as kidney damage, dangerously high potassium levels, and severe allergic reactions.

Quick Summary

This article details key drug interactions with ACE inhibitors, highlighting medications to avoid due to risks like kidney injury, high potassium, and severe swelling. It covers interactions with NSAIDs, other blood pressure drugs, potassium supplements, and lithium, emphasizing the importance of expert consultation.

Key Points

Avoid NSAIDs with Diuretics and ACE Inhibitors: The combination can cause acute kidney injury, a condition known as the 'triple whammy'.
Watch for High Potassium Levels: Be aware that ACE inhibitors, potassium-sparing diuretics, and potassium supplements can all raise potassium levels, posing a hyperkalemia risk.
Do Not Combine with ARBs or Aliskiren: Taking an ACE inhibitor with another drug in the same class (ARBs) or with Aliskiren can increase the risk of side effects like hyperkalemia and kidney damage.
Follow Wash-out Period with Entresto: A 36-hour gap is required when switching between an ACE inhibitor and the heart failure medication Entresto to prevent life-threatening angioedema.
Monitor Lithium Closely: ACE inhibitors can increase lithium concentration in the body, which can lead to toxicity; regular monitoring is crucial.
Inform Doctor About All Medications: Always disclose all medications, including over-the-counter drugs, supplements, and herbal products, to your healthcare provider to manage potential interactions.
Contraindicated in Pregnancy: Pregnant individuals or those planning a pregnancy should not take ACE inhibitors due to the risk of birth defects.

Understanding ACE Inhibitors and Potential Risks

Angiotensin-converting enzyme (ACE) inhibitors, such as lisinopril, ramipril, and enalapril, are widely prescribed to treat high blood pressure, heart failure, and protect kidney function, especially in people with diabetes. They work by relaxing blood vessels and lowering blood pressure, but their mechanism of action makes them susceptible to significant interactions with other drugs. These interactions can lead to serious health issues, emphasizing the importance of informing your healthcare provider and pharmacist about all medications, supplements, and herbal products you are taking.

The 'Triple Whammy': NSAIDs and Diuretics

One of the most dangerous combinations is the so-called 'triple whammy,' which involves taking an ACE inhibitor, a diuretic (water pill), and a nonsteroidal anti-inflammatory drug (NSAID) together. This combination significantly increases the risk of acute kidney injury, particularly in older adults or those with pre-existing kidney problems.

ACE Inhibitors: Lower blood pressure and affect kidney function.
Diuretics: Reduce fluid volume, which can decrease blood flow to the kidneys.
NSAIDs: Constrict the blood vessels leading into the kidneys, further reducing blood flow.

Individually, these drugs may have limited impact, but together, they can overwhelm the kidney's ability to regulate blood flow and function, leading to serious renal issues. Common over-the-counter NSAIDs to be aware of include ibuprofen (Advil, Motrin) and naproxen (Aleve).

Medications that Elevate Potassium Levels

ACE inhibitors can cause an increase in blood potassium levels (hyperkalemia) by reducing aldosterone production. Combining ACE inhibitors with other medications or supplements that also increase potassium can lead to dangerously high potassium levels, potentially causing irregular heart rhythms.

Medications and supplements to avoid or use with caution:

Potassium-sparing diuretics: Examples include spironolactone and amiloride, which cause the body to retain potassium.
Potassium supplements: These can be found as standalone pills or within electrolyte supplements.
Certain salt substitutes: Many salt substitutes replace sodium with potassium.
Other drugs: Some antibiotics like sulfamethoxazole/trimethoprim can also raise potassium levels.

Monitoring blood potassium levels is essential for anyone taking these combinations.

Interactions with Other Blood Pressure Medications

Certain other medications used for blood pressure or heart failure can have dangerous interactions when combined with an ACE inhibitor. The following should generally be avoided:

Angiotensin II Receptor Blockers (ARBs): Like ACE inhibitors, ARBs block components of the renin-angiotensin-aldosterone system. Combining them offers no significant additional benefit and substantially increases the risk of kidney damage and hyperkalemia.
Direct Renin Inhibitors (e.g., Aliskiren): This combination is contraindicated, especially in patients with diabetes, due to the high risk of kidney damage, low blood pressure, and hyperkalemia.
Neprilysin Inhibitors (e.g., Sacubitril in Entresto): It is contraindicated to take an ACE inhibitor with Entresto. There must be a 36-hour wash-out period when switching between these medications to avoid the risk of severe angioedema.

Table of Common ACE Inhibitor Interactions


Interacting Medication	ACE Inhibitor Interaction	Associated Health Risk	Management Strategy
NSAIDs (ibuprofen, naproxen)	Impairs kidney function, increases blood pressure, reduces ACE inhibitor effectiveness.	Acute kidney injury, increased blood pressure.	Avoid long-term concurrent use; discuss safer pain relief options with a doctor.
Potassium-sparing Diuretics	Increases potassium levels in the blood.	Hyperkalemia, which can cause dangerous heart rhythms.	Monitor blood potassium levels regularly; dose adjustment or alternative therapy may be necessary.
Angiotensin II Receptor Blockers (ARBs)	Increases risk of hyperkalemia, low blood pressure, and kidney damage.	Kidney damage, very low blood pressure.	Combination is not recommended; alternative blood pressure strategies should be used.
Lithium	Reduces lithium clearance by the kidneys.	Lithium toxicity, with symptoms like tremors, dizziness, and blurry vision.	Monitor lithium levels frequently; dose adjustment may be required.
Aliskiren (Direct Renin Inhibitor)	Increases risk of kidney damage, low blood pressure, and high potassium.	Severe kidney problems, particularly in people with diabetes.	Contraindicated, especially in patients with diabetes.
Neprilysin Inhibitors (e.g., Entresto)	Increases the risk of angioedema.	Severe and potentially life-threatening swelling of the face, tongue, and throat.	Contraindicated; requires a 36-hour wash-out period.
Potassium Supplements	Leads to high blood potassium levels.	Hyperkalemia and cardiac issues.	Avoid supplements and high-potassium salt substitutes unless advised by a doctor.

Other Important Medication and Condition Considerations

Beyond these major drug-drug interactions, several other factors require careful management when taking ACE inhibitors:

Pregnancy and Breastfeeding: ACE inhibitors are contraindicated during pregnancy due to the risk of birth defects and should be avoided when breastfeeding as well. Alternative treatments are necessary for pregnant or nursing individuals requiring blood pressure management.
Diabetes: Individuals with diabetes are at a higher risk of complications, including kidney damage and hyperkalemia, when combining certain interacting medications with an ACE inhibitor. The interaction with aliskiren is particularly risky. Blood glucose levels should also be closely monitored, as ACE inhibitors can increase sensitivity to insulin or oral antidiabetic agents.
Chronic Kidney Disease: Patients with pre-existing kidney disease have a higher risk of adverse effects from ACE inhibitor interactions. They may require closer monitoring of kidney function, especially when other interacting medications are added.
Hypovolemia: Dehydration or low fluid volume can be worsened by ACE inhibitors, leading to severely low blood pressure (hypotension). This can be exacerbated by conditions causing fluid loss, like vomiting or diarrhea.
Injectable Gold (Sodium Aurothiomalate): In rare cases, a reaction similar to nitrite poisoning, including flushing and nausea, has been reported when injectable gold is combined with ACE inhibitors.
Immunosuppressants: Certain medications like mTOR inhibitors (sirolimus, everolimus) used after organ transplants or for cancer can increase the risk of angioedema when taken with ACE inhibitors.

The Critical Role of Your Healthcare Team

Managing medications is a complex process that requires open communication with your healthcare providers. This includes your doctor, pharmacist, and any other specialists involved in your care. Before starting any new medication, supplement, or even using salt substitutes, you should consult with your healthcare team to review potential interactions. They can help you determine the safest treatment plan and monitor you for any side effects. It is also important not to suddenly stop taking an ACE inhibitor without medical guidance, as this can have serious consequences.

For ongoing management, your doctor may recommend regular blood tests to check your potassium levels and kidney function, especially if you are taking a combination of drugs that affects these systems. Understanding what medication should be avoided with ACE inhibitors is a vital step in taking an active role in your health and safety. The potential risks are serious, but with proper precautions and monitoring, ACE inhibitors remain a highly effective treatment for many cardiovascular conditions. For more information on ACE inhibitor safety, consider consulting reputable sources like the National Library of Medicine (NCBI) for detailed pharmacology reports.

Frequently Asked Questions

You should use caution when taking ibuprofen or other NSAIDs with an ACE inhibitor. Chronic use, especially when combined with a diuretic, can increase the risk of kidney damage. For occasional pain relief, consult your doctor for a safer alternative.

Many salt substitutes contain high levels of potassium chloride. Since ACE inhibitors can increase blood potassium levels, using these substitutes can lead to hyperkalemia. It is best to avoid them unless specifically advised and monitored by your healthcare provider.

The combination of an ACE inhibitor and a potassium-sparing diuretic can significantly increase the risk of hyperkalemia (high blood potassium levels). This can cause serious heart problems. If this combination is necessary, a doctor must closely monitor potassium levels.

Both ARBs and ACE inhibitors act on the same system that regulates blood pressure. Combining them does not provide extra benefit for most patients but increases the risk of side effects like high potassium and kidney damage. It is generally recommended to avoid combining these two classes of drugs.

Angioedema is a rare but serious side effect of ACE inhibitors, causing swelling of the face, tongue, and throat that can be life-threatening if breathing is obstructed. The risk is significantly increased when ACE inhibitors are taken with neprilysin inhibitors like sacubitril (in Entresto).

You must wait at least 36 hours when switching between an ACE inhibitor and the heart failure medication Entresto (sacubitril/valsartan). This is to avoid the heightened risk of angioedema.

Yes, ACE inhibitors can reduce the kidneys' ability to clear lithium, leading to a build-up of toxic levels. Individuals taking this combination should be regularly monitored for signs of lithium toxicity, such as tremors, dizziness, or confusion.