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Patients taking the commonly prescribed diuretic spironolactone should be aware that it has clinically important interactions with many other commonly used prescription and over-the-counter medications.
Spironolactone is known as a potassium-sparing diuretic because it results in significantly less excretion of potassium into the urine than do other diuretics, such hydrochlorothiazide (MICROZIDE) and furosemide (LASIX). Spironolactone is available as a single-active-ingredient product...
Patients taking the commonly prescribed diuretic spironolactone should be aware that it has clinically important interactions with many other commonly used prescription and over-the-counter medications.
Spironolactone is known as a potassium-sparing diuretic because it results in significantly less excretion of potassium into the urine than do other diuretics, such hydrochlorothiazide (MICROZIDE) and furosemide (LASIX). Spironolactone is available as a single-active-ingredient product under the brand names ALDACTONE and CAROSPIR, which Public Citizen’s Health Research Group has designated as Limited Use. It also is marketed in combination with the diuretic hydrochlorothiazide under the brand name ALDACTAZIDE, which we have designated as Do Not Use.
Spironolactone was first marketed in the U.S. in 1960 and is approved by the Food and Drug Administration (FDA) for the treatment of certain patients with any of the following disorders:
- moderate-to-severe heart failure
- hypertension (high blood pressure)
- edema (swelling) due to liver cirrhosis
- primary hyperaldosteronism (excess production of the hormone aldosterone by the adrenal glands).[1]
Interactions causing hyperkalemia
Concomitant (simultaneous) use of spironolactone with many other medications may lead to hyperkalemia (high blood potassium levels), which can lead to potentially dangerous abnormal heart rhythms (see Table, below). The list of such interacting drugs includes angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), other potassium-sparing diuretics, the renin inhibitor aliskiren (TEKTURNA) and nonsteroidal anti-inflammatory drugs (NSAIDs).[2],[3]
ACE inhibitors are a large class of drugs that are all approved by the FDA to treat hypertension. Certain ACE inhibitors also are approved to treat one or more of the following: heart failure, heart attacks, other types of cardiovascular disease and diabetic kidney disease.
ARBs are another class of drugs used to treat hypertension. Some ARBs also are used to treat heart failure and slow the progression of chronic kidney disease.
Like spironolactone, other potassium-sparing diuretics are used to treat certain patients with hypertension and heart failure. Importantly, two different potassium-sparing diuretics should never be used concomitantly because the risk of hyperkalemia is too high.
Finally, aliskiren also is used to treat hypertension; it inhibits the blood-pressure–raising substance renin.
ACE inhibitors, ARBs, potassium-sparing diuretics and aliskiren all act on a biological pathway central to the regulation of blood pressure and the body’s sodium and potassium balance, known as the renin-angiotensin-aldosterone system. Blocking any part of this system leads to decreased excretion of potassium into the urine. Combining any of these drugs enhances these effects on urinary potassium excretion, thus increasing the risk of hyperkalemia. Patients using spironolactone concomitantly with any of these other drugs should have their blood potassium level checked periodically.
Examples of Oral Drugs That When Used Concomitantly With Spironolactone Can Cause Hyperkalemia
| Drug Category | Generic Drug Name (Brand Name[s]) |
|---|---|
| Angiotensin-converting enzyme inhibitors |
|
| Angiotensin receptor blockers |
|
| Nonsteroidal anti-inflammatory drugs |
|
| Potassium-sparing diuretics |
|
| Renin inhibitor |
|
†Combination brand-name products not listed
*Designated as Limited Use by Worst Pills, Best Pills News
**Designated as Do Not Use by Worst Pills, Best Pills News
NSAIDs
NSAIDs — such as ibuprofen (ADVIL, MIDOL LIQUID GELS, MOTRIN IB, TAB-PROFEN) and naproxen (ALEVE, ANAPROX DS, EC-NAPROSYN, NAPRELAN, NAPROSYN), which are available in both prescription and over-the-counter versions — are widely used to treat pain and inflammation due to arthritis and a wide array of other disorders.
In addition to increasing the risk of hyperkalemia, concomitant use of NSAIDs in some patients can reduce the diuretic effects of spironolactone, thus impairing its effectiveness in treating hypertension, heart failure and edema due to cirrhosis. Such concomitant use also may cause kidney damage.
Lithium (LITHOBID)
Lithium is a mood-stabilizing drug that is used to treat bipolar disorder, also known as manic depression, a chronic mental illness that causes unusual shifts in mood, energy and activity levels.
Use of spironolactone in combination with lithium may cause blood lithium to increase to toxic levels. Nausea, diarrhea, vomiting, loss of appetite, drowsiness, muscle weakness and decreased coordination are early signs of lithium toxicity. With increasing blood lithium levels, patients can experience giddiness, ataxia (severe lack of muscle control or coordination of voluntary movements), slurred speech, blurred vision, tinnitus (perception of noise or ringing in the ears) and markedly increased urine output. Severe lithium toxicity can lead to seizures, coma, abnormal heart rhythms and even death.
Patients taking spironolactone concomitantly with lithium therapy should undergo periodic blood tests to check lithium levels, and their lithium dosage should be adjusted as needed to maintain blood lithium levels in the desired range. Such patients also should be monitored closely for symptoms of lithium toxicity.
What You Can Do
If you need treatment with spironolactone, review all of your other medications with your doctor to assess for potentially significant drug interactions. If you are taking certain medications that interact with spironolactone, you may need to adjust the dosage of the interacting drug or undergo more frequent monitoring of the blood levels of the interacting drug or of your blood potassium levels and kidney function, or your doctor may advise you to take a different drug. Be aware that other drugs not listed in this article also may have dangerous interactions with spironolactone.
References
[1] Pfizer. Label: spironolactone (ALDACTONE). June 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/012151s077lbl.pdf. Accessed August 4, 2022.
[2] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “spironolactone.” Accessed August 4, 2022.
[3] Pfizer. Label: spironolactone (ALDACTONE). June 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/012151s077lbl.pdf. Accessed August 4, 2022.
