Indomethacin with Eplerenone Interaction Details
Brand Names Associated with Indomethacin
- Indocin®
- Indomethacin
- Tivorbex®
Brand Names Associated with Eplerenone
- Eplerenone
- Inspra®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Jan 02, 2024
Interaction Effect
Increased serum potassium levels or acute renal failure
Interaction Summary
Risk of renal toxicity is increased with combined use of NSAIDs and diuretics due to dose-dependent reduction in prostaglandin formation and in renal blood flow. NSAIDs, such as indomethacin, and potassium-sparing diuretics are both associated with increased levels of serum potassium and combined use may lead to severe hyperkalemia. Additionally, the diuretic, antihypertensive, and natriuretic effect of the diuretic may be reduced in some patients by concurrent use with an NSAID . Consider potential effects on potassium levels and renal function when coadministering these drugs. Monitor for signs of worsening renal function and for efficacy of the diuretic, including antihypertensive effects . Consider monitoring serum potassium levels .
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Risk of renal toxicity is increased with combined use of NSAIDs and diuretics due to dose-dependent reduction in prostaglandin formation and in renal blood flow. NSAIDs, such as indomethacin, and potassium-sparing diuretics are both associated with increased levels of serum potassium and combined use may lead to severe hyperkalemia. Additionally, the diuretic, antihypertensive, and natriuretic effect of the diuretic may be reduced in some patients by concurrent use with an NSAID . Consider potential effects on potassium levels and renal function when coadministering these drugs. Monitor for signs of worsening renal function and for efficacy of the diuretic, including antihypertensive effects . Consider monitoring serum potassium levels .
Mechanism Of Interaction
Additive effects on serum potassium; decreased renal prostaglandin synthesis
Literature Reports
A) The effect of indomethacin in subjects treated with triamterene (200 mg daily) or spironolactone (300 mg daily) was investigated. Triamterene alone, but not spironolactone, provoked a rise in urinary prostaglandins E2 and F2 alpha. After indomethacin, urinary prostaglandins were suppressed. The natriuretic effect of spironolactone was reduced by 54%, whereas the natriuresis induced by triamterene was unchanged. No correlation was found between urinary prostaglandin E2 and F2 alpha and natriuresis. When triamterene was administered with indomethacin, 2 subjects developed reversible acute renal failure. Diflunisal, a structurally unrelated NSAID, was given to 12 of the subjects and provoked similar interactions with spironolactone. The results suggest that prostaglandins contribute to the natriuretic effects of spironolactone, but not to those of triamterene .
B) The formation of crystals and casts occurred in the medullary and papillary collecting ducts of the kidney. These findings provide a possible explanation for the reported nephrotoxicity of triamterene, particularly when given to patients who are receiving NSAIDs. The precipitation of crystals in acidic urine is unlikely to be a class effect of potassium-sparing diuretics, and acute renal failure as a result of cotherapy with NSAIDs and amiloride or spironolactone has not been reported .
C) A base cohort study involving 10,519 patients older than 55 years who were receiving NSAIDs and diuretics was conducted to investigate the relationship between congestive heart failure (CHF) and the use of these 2 classes of drugs. The patient population was 72.2% female, with an average age of 70.8 years. During periods of concomitant NSAID and diuretic use, the risk of hospitalization for CHF was twice that of periods of diuretic use only. Patients who used diuretics on a regular basis also had an increased risk of hospitalization due to CHF compared with irregular users of diuretics. A combination of a thiazide and a potassium-sparing diuretic was the most frequently used diuretic type, and the incidence density of hospitalizations during times of use with this combination and a NSAID resulted in a 3-fold increase over that for diuretic use only .
Indomethacin Overview
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Indomethacin is used to relieve moderate to severe pain, tenderness, swelling, and stiffness caused by osteoarthritis (arthritis caused by a breakdown of the lining of the joints), rheumatoid arthritis (arthritis caused by swelling of the lining of the joints), and ankylosing spondylitis (arthritis that mainly affects the spine). Indomethacin is also used to treat pain in the shoulder caused by bursitis (inflammation of a fluid-filled sac in the shoulder joint) and tendinitis (inflammation of the tissue that connects muscle to bone). Indomethacin immediate-release capsules and suspension (liquid) are also used to treat acute gouty arthritis (attacks of severe joint pain and swelling caused by a build-up of certain substances in the joints). Indomethacin is in a class of medications called NSAIDs. It works by stopping the body's production of a substance that causes pain, fever, and inflammation.
Eplerenone Overview
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Eplerenone is used alone or in combination with other medications to treat high blood pressure. Eplerenone is in a class of medications called mineralocorticoid receptor antagonists. It works by blocking the action of aldosterone, a natural substance in the body that raises blood pressure.
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High blood pressure is a common condition and when not treated, can cause damage to the brain, heart, blood vessels, kidneys and other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart failure, stroke, kidney failure, loss of vision, and other problems. In addition to taking medication, making lifestyle changes will also help to control your blood pressure. These changes include eating a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 minutes most days, not smoking, and using alcohol in moderation.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.