What medication should you not take with spironolactone? A guide to dangerous drug interactions

October 14, 2025 •

3 min read

According to one study, combining spironolactone with other medications that increase potassium levels significantly elevates the risk of life-threatening hyperkalemia. It is crucial to understand what medication should you not take with spironolactone to prevent potentially dangerous interactions.

Quick Summary

This guide details the major drug interactions to avoid when taking spironolactone, focusing on the risks of hyperkalemia from combining it with potassium-sparing diuretics, ACE inhibitors, and ARBs. It also covers the risks associated with NSAIDs, lithium, and digoxin.

Key Points

Avoid Potassium Supplements: Do not take potassium supplements or use potassium-containing salt substitutes while on spironolactone, as this can cause dangerous hyperkalemia.
Caution with ACE Inhibitors and ARBs: Combining spironolactone with these blood pressure medications significantly increases the risk of high potassium levels.
Limit NSAID Use: Nonsteroidal anti-inflammatory drugs like ibuprofen can reduce spironolactone's effectiveness and increase the risk of kidney problems.
Report All Medications: Always inform your doctor and pharmacist of all prescription and over-the-counter medications, supplements, and herbal products you are taking.
Watch for Hyperkalemia Symptoms: Be aware of signs of high potassium, including muscle weakness, tingling, or irregular heartbeat, and seek immediate medical attention if they occur.
Strict Monitoring is Key: If you must take interacting medications, your doctor will likely require frequent blood tests to monitor potassium and kidney function.

Spironolactone is a prescription medication used to treat conditions such as heart failure, high blood pressure, and fluid retention (edema). As a potassium-sparing diuretic, it helps the body remove excess water and sodium while retaining potassium. Combining spironolactone with certain drugs or supplements can lead to dangerously high potassium levels (hyperkalemia). Understanding these interactions is vital for patient safety.

Primary Drug Interactions to Avoid

Certain medications and supplements can increase the risk of hyperkalemia or affect how spironolactone works in the body. It is crucial to inform healthcare providers of all substances being taken.

Potassium Supplements and Potassium-Containing Salt Substitutes

Combining spironolactone with additional potassium sources significantly increases the risk of severe hyperkalemia. Spironolactone already reduces potassium excretion, so adding more potassium can overwhelm the body's ability to regulate levels. Avoid these products unless directed by a doctor.

ACE Inhibitors and Angiotensin II Receptor Blockers (ARBs)

ACE inhibitors (like lisinopril, enalapril, and ramipril) and ARBs (like losartan and valsartan) are blood pressure medications that also increase potassium levels. Taking them with spironolactone creates a heightened risk of severe hyperkalemia, requiring close monitoring of serum potassium.

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

NSAIDs, such as ibuprofen, naproxen, and celecoxib, can reduce the effectiveness of spironolactone and increase the risk of kidney problems and elevated potassium levels.

Other Potassium-Sparing Diuretics

Combining spironolactone with other diuretics that also conserve potassium, such as eplerenone or amiloride, is not recommended due to a significantly increased risk of life-threatening hyperkalemia.

Lithium

Spironolactone can interfere with the kidneys' ability to remove lithium, potentially leading to increased lithium levels and toxicity. Symptoms of lithium toxicity include nausea, vomiting, tremors, and confusion. Patients taking this combination need close monitoring of lithium levels.

Digoxin

Spironolactone can increase the amount of digoxin in the body, raising the risk of digoxin toxicity. Signs of toxicity include vision changes and irregular heartbeats. Careful monitoring and dosage adjustments are necessary.

Drug Interaction Comparison: Spironolactone


Drug Type	Examples	Primary Interaction	Resulting Risk	Management Strategy
Potassium Supplements	Sando K tablets, potassium chloride	Additive effect, increasing body's potassium load.	High risk of severe hyperkalemia.	Avoid use unless directed by a doctor.
ACE Inhibitors	Lisinopril, Enalapril	Both increase potassium levels.	High risk of severe hyperkalemia and kidney problems.	Close monitoring of potassium and kidney function.
ARBs	Losartan, Valsartan	Both increase potassium levels.	High risk of severe hyperkalemia and kidney problems.	Close monitoring of potassium and kidney function.
NSAIDs	Ibuprofen, Naproxen, Aspirin	Reduced spironolactone efficacy; increased risk of kidney issues.	Increased blood pressure, hyperkalemia, renal impairment.	Avoid or monitor closely; consider acetaminophen.
Other K-Sparing Diuretics	Eplerenone, Amiloride	Additive potassium-sparing effect.	High risk of severe hyperkalemia.	Avoid combination; choose one.
Lithium	Lithobid	Decreased renal clearance of lithium.	Increased risk of lithium toxicity.	Frequent monitoring of serum lithium levels.
Digoxin	Lanoxin	Increased serum digoxin levels.	Increased risk of digoxin toxicity.	Careful dosage adjustments and monitoring.

What to Do If You Take Interacting Medications

If you are taking spironolactone and are prescribed or start taking any potentially interacting medication, it's vital to discuss this with your doctor and pharmacist. They can assess the risk and determine the safest approach, which might involve:

Monitoring: Regular blood tests to check potassium levels and kidney function are often necessary.
Dosage Adjustment: The dose of one or both medications may be altered.
Alternative Medications: Switching to different drugs might be the safest option.
Symptom Awareness: Be alert for signs of hyperkalemia, like muscle weakness, tingling, or an irregular heartbeat, and get immediate medical help if they occur.

Conclusion

Spironolactone is effective but requires careful attention to drug interactions. The main risk comes from combining it with substances that increase potassium, like supplements, ACE inhibitors, and ARBs, which can cause life-threatening hyperkalemia. Interactions with NSAIDs, lithium, and digoxin can also cause problems by affecting efficacy or increasing toxicity. Always communicate openly with your healthcare team to ensure safe treatment.

For more detailed information on drug interactions and medication safety, consult with a qualified healthcare professional. Reliable information can also be found from resources like the U.S. National Library of Medicine's MedlinePlus database.

Frequently Asked Questions

Spironolactone is a potassium-sparing diuretic that can cause high potassium levels (hyperkalemia). Combining it with other medications that also raise potassium levels, such as ACE inhibitors and ARBs, can lead to dangerously high potassium and serious cardiac issues.

It is generally not recommended to take NSAIDs like ibuprofen or naproxen with spironolactone. The combination can make spironolactone less effective and increase the risk of kidney problems and elevated potassium levels.

No, potassium supplements are not safe to take with spironolactone unless specifically instructed by your doctor. Spironolactone's potassium-sparing effect combined with extra potassium can cause dangerous hyperkalemia.

Combining spironolactone with lithium can increase the concentration of lithium in the blood, raising the risk of lithium toxicity. This is because spironolactone can reduce the kidneys' ability to clear lithium.

Both ACE inhibitors (e.g., lisinopril) and ARBs (e.g., losartan) can increase the body's potassium levels. When combined with spironolactone, this effect is magnified, significantly raising the risk of hyperkalemia.

Symptoms of hyperkalemia include muscle weakness, fatigue, tingling or numbness, nausea, and irregular heart palpitations. If you experience any of these, contact your doctor immediately.

You should not take spironolactone with other potassium-sparing diuretics like eplerenone or amiloride. However, your doctor may combine it with a potassium-wasting diuretic (like furosemide) while closely monitoring your potassium levels.