Which Drug Should Not Be Used with Spironolactone? A Critical Guide to Avoiding Dangerous Interactions

October 14, 2025 •

4 min read

Approximately 1 in 5 people taking certain combinations of heart medication, including spironolactone, are at a higher risk of developing dangerously high potassium levels. Therefore, understanding which drug should not be used with spironolactone is a critical step in managing your health safely and effectively.

Quick Summary

Reviewing spironolactone's dangerous drug interactions is vital for patient safety. This resource details medications like ACE inhibitors, ARBs, and NSAIDs that must be used with caution due to serious side effects.

Key Points

Hyperkalemia Risk: Combining spironolactone with ACE inhibitors, ARBs, potassium supplements, or other potassium-sparing diuretics can cause dangerously high potassium levels.
NSAID and Kidney Damage: Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen can increase the risk of kidney problems and decrease spironolactone's effectiveness.
Digoxin and Lithium Toxicity: Spironolactone can raise the blood levels of digoxin and lithium, leading to potentially toxic effects and increased side effects.
Avoid High-Potassium Foods: Be cautious with potassium-rich foods and avoid potassium-containing salt substitutes to prevent hyperkalemia.
Consult Your Healthcare Provider: Always inform your doctor or pharmacist about all medications, supplements, and foods you consume to avoid harmful drug interactions.
Monitor Potassium Levels: Regular blood tests are essential to monitor potassium and kidney function, especially when combining spironolactone with other medications.

Spironolactone is a potassium-sparing diuretic, meaning it helps the body eliminate excess sodium and fluid while retaining potassium. This unique mechanism is beneficial for treating conditions like heart failure, high blood pressure, and edema (fluid retention). However, this potassium-retaining effect is also the primary reason for many dangerous drug interactions. Combining spironolactone with other medications that increase potassium levels can lead to hyperkalemia, a potentially life-threatening condition.

Medications that dangerously raise potassium levels

ACE Inhibitors and ARBs

Angiotensin-converting enzyme (ACE) inhibitors (like lisinopril, enalapril, and captopril) and Angiotensin II receptor blockers (ARBs) (like losartan and valsartan) are commonly prescribed for high blood pressure and heart failure. Both of these drug classes, along with spironolactone, contribute to an increase in blood potassium levels. The concurrent use of spironolactone with an ACE inhibitor or ARB significantly elevates the risk of severe hyperkalemia. While physicians may carefully co-prescribe these medications in some heart failure patients, this is always accompanied by frequent blood tests to monitor potassium levels.

Potassium-sparing diuretics and supplements

Using spironolactone alongside other potassium-sparing diuretics, such as eplerenone, amiloride, or triamterene, is contraindicated. Since these drugs function similarly by preventing potassium loss, taking them together creates an extreme risk of hyperkalemia. The same risk applies to using potassium supplements or potassium-containing salt substitutes. Spironolactone is designed to spare potassium, so adding more potassium into your system through supplements or diet can easily push levels into a dangerous range.

Other potassium-raising medications

Other medications can also increase potassium levels. These include certain types of heparin (a blood thinner) and the antibiotic trimethoprim. A healthcare provider needs to carefully evaluate the risks versus benefits before prescribing these drugs in combination with spironolactone.

Drugs with increased toxicity risks

Digoxin

Digoxin is a medication used to treat certain heart conditions, including heart failure and atrial fibrillation. Spironolactone can interfere with the body's ability to clear digoxin from the system, which can increase digoxin levels in the blood and lead to toxicity. Symptoms of digoxin toxicity include vision changes, nausea, dizziness, and heart rhythm problems. If this combination is necessary, careful monitoring and dose adjustments are required.

Lithium

Lithium is a mood stabilizer used to treat bipolar disorder. Spironolactone can reduce the kidneys' ability to excrete lithium, causing blood lithium levels to rise. Elevated lithium levels can become toxic, leading to symptoms like nausea, vomiting, diarrhea, tremors, muscle weakness, and confusion. Patients taking this combination must have their lithium levels closely monitored.

Cholestyramine

Cholestyramine is a cholesterol-lowering medication that, when taken with spironolactone, can increase potassium levels and cause metabolic acidosis, an imbalance of acids and bases in the body. This combination should be used with extreme caution.

Medications that reduce spironolactone's effectiveness

Nonsteroidal anti-inflammatory drugs (NSAIDs)

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil, Motrin), naproxen (Aleve), and celecoxib (Celebrex), are common over-the-counter pain relievers. Taking NSAIDs with spironolactone can make the diuretic less effective by promoting fluid and sodium retention. This can raise blood pressure and increase the risk of hyperkalemia and kidney problems, especially in those with heart failure or pre-existing kidney issues.

Other interacting substances

Abiraterone: This prostate cancer medication can be less effective when combined with spironolactone because spironolactone can bind to the same receptors.
Licorice: Consuming large quantities of licorice extract can decrease spironolactone's therapeutic effect.

Comparison of Pain Relief Options with Spironolactone


Medication Type	Examples	Interaction with Spironolactone	Safety Profile
NSAIDs	Ibuprofen (Advil), Naproxen (Aleve), Celecoxib (Celebrex)	Decreased spironolactone effectiveness, increased risk of kidney problems and hyperkalemia.	Caution: Generally avoid. Consult a doctor before use.
Acetaminophen	Tylenol	No known significant interaction.	Generally safer for pain relief.
Aspirin	Low-dose aspirin may be an exception for certain conditions under a doctor's guidance.	Can reduce spironolactone effectiveness; increased risk of bleeding.	Caution: Avoid high doses or regular use without a doctor's approval.

What to do before starting spironolactone

Before you start spironolactone, it is essential to provide your healthcare provider with a complete list of all medications, supplements, and herbal products you are taking. This allows them to screen for potential interactions, adjust dosages, or recommend safer alternatives. Your doctor will also consider your medical history, including any pre-existing kidney issues, heart problems, or electrolyte imbalances. Close monitoring of your potassium levels and kidney function through blood tests will likely be part of your treatment plan.

Conclusion

Spironolactone is an important medication for many conditions, but its potassium-sparing nature necessitates vigilance against a range of drug interactions. The primary danger comes from combining it with other substances that increase potassium, such as ACE inhibitors, ARBs, and potassium supplements, which can lead to life-threatening hyperkalemia. Additionally, combining spironolactone with NSAIDs can reduce its effectiveness and increase the risk of kidney damage, while interactions with digoxin or lithium can cause dangerous levels of those drugs to accumulate. Patients should never stop or change their medication regimen without consulting a healthcare professional first. The safest approach is always to maintain open communication with your medical team to ensure all interactions are managed safely and effectively.

For more specific information on drug interactions and how they affect the body, consult reliable sources like the U.S. National Library of Medicine's MedlinePlus drug information.

Frequently Asked Questions

No, many salt substitutes contain potassium chloride, which can lead to dangerously high potassium levels (hyperkalemia) when combined with spironolactone. Avoid these products unless explicitly instructed by your doctor.

Symptoms can include muscle weakness, tingling or numbness, nausea, and irregular heartbeat. Seek immediate medical attention if you experience these, as it can be life-threatening.

NSAIDs like ibuprofen and naproxen should generally be avoided. Acetaminophen (Tylenol) is often a safer alternative for pain relief, but you should always consult your doctor first.

Do not panic. Contact your doctor or pharmacist immediately for guidance. They can assess the risk based on the specific drugs, dosages, and your health status.

Your doctor will likely order regular blood tests to check your potassium levels and kidney function, especially when starting or adjusting doses, to ensure your safety.

Always tell your healthcare provider about any herbal products you take. Some, like dandelion, can affect electrolyte balance or have diuretic effects and may interact negatively with spironolactone.

Yes. Be mindful of your diet, avoiding potassium supplements and potassium-rich salt substitutes. Excessive licorice consumption should also be avoided. Additionally, maintain adequate hydration.