Aspirin with Spironolactone Interaction Details

Brand Names Associated with Aspirin

Brand Names Associated with Spironolactone

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Mar 04, 2024

Interaction Effect

Reduced diuretic effectiveness, hyperkalemia, or possible nephrotoxicity

Interaction Summary

NSAIDs may negate the diuretic and antihypertensive effects of potassium-sparing diuretics[1]. Acute reversible renal failure has been reported [2][3][4]. NSAIDs may cause hyperkalemia by inducing hyporeninemic hypoaldosteronism. Thus, additive effects on potassium homeostasis may occur [5]. When coadministered, monitor for worsening renal function and assure diuretic efficacy, including blood pressure [6]. Consider monitoring serum potassium levels [7].

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Concomitant use of NSAIDs and diuretics may increase the risk of renal toxicity[8]. Severe hyperkalemia has been reported with use of NSAIDs (eg, indomethacin) and potassium-sparing diuretics. The diuretic, antihypertensive, and natriuretic effect of the diuretic may be reduced in some patients by concurrent use with an NSAID [9]. When concomitant use is necessary, monitor for signs of worsening renal function and assure diuretic efficacy, including appropriate effects on blood pressure [6][10]. Consider monitoring serum potassium levels [7].

Mechanism Of Interaction

Decreased renal prostaglandin synthesis

Literature Reports

A) Coadministration of a single oral dose of spironolactone 50 mg with aspirin significantly reduced urinary excretion and fractional excretion of the major active metabolite of spironolactone in a study of patients 23 to 28 years old (N=6) [11].

B) 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 [12].

C) 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 [13].

D) 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 [14].

References

1 ) Davis A, Day RO, & Begg EJ: Interactions between non-steroidal anti-inflammatory drugs and antihypertensives and diuretics. Aust N Z J Med 1986; 16:537-546.

2 ) Mathews A & Baillie FR: Acute renal failure and hyperkalaemia associated with triamterene and indomethacin. Vet Hum Toxicol 1986; 28:224-225.

3 ) Favre L, Glasson P, & Vallotton MB: Reversible acute renal failure from combined triamterene and indomethacin. Ann Intern Med 1982; 96:317-320.

4 ) Weinberg MS, Quigg RJ, Salant DJ, et al: Anuric renal failure precipitated by indomethacin and triamterene. Nephron 1985; 40:216-218.

5 ) Mor R, Pitlik S, & Rosenfeld JB: Indomethacin- and Moduretic-induced hyperkalemia. Isr J Med Sci 1983; 19:535-537.

6 ) Product Information: MOBIC(R) oral tablets, oral suspension, meloxicam oral tablets, oral suspension. Boehringer Ingelheim Pharmaceuticals, Inc. (per FDA), Ridgefield, CT, 2016.

7 ) Product Information: INSPRA(R) oral tablets, eplerenone oral tables. GD Searle (per FDA), New York, NY, 2016.

8 ) Product Information: ANAPROX(R) oral tablets, naproxen sodium oral tablets. Canton Laboratories, LLC (per FDA), Alpharetta, GA, 2016.

9 ) Product Information: Aldactazide(R) oral tablets, spironolactone hydrochlorothiazide oral tablets. G.D. Searle (per FDA), New York, NY, 2014.

10 ) Product Information: CALDOLOR(R) intravenous injection, ibuprofen intravenous injection. Cumberland Pharmaceuticals Inc. (per FDA), Nashville, TN, 2016.

11 ) Ramsay L, Shelton J, Harrison I, et al: Spironolactone and potassium canrenoate in normal man. Clin Pharmacol Ther 1976; 20:167-177.

12 ) Favre L, Glasson P, Riondel A, et al: Interaction of diuretics and non-steroidal anti-inflammatory drugs in man. Clin Sci (Lond) 1983; 64(4):407-415.

13 ) Fairley KF, Woo KT, Birch DF, et al: Triamterene-induced crystalluria and cylinduria: clinical and experimental studies. Clin Nephrol 1986; 26:169-173.

14 ) Heerdink ER, Leufkens HG, Herings RMC, et al: NSAIDs associated with increased risk of congestive heart failure in elderly patients taking diuretics. Arch Intern Med 1998; 158:1108-1112.

Aspirin Overview

• Prescription aspirin is used to relieve the symptoms of rheumatoid arthritis (arthritis caused by swelling of the lining of the joints), osteoarthritis (arthritis caused by breakdown of the lining of the joints), systemic lupus erythematosus (condition in which the immune system attacks the joints and organs and causes pain and swelling) and certain other rheumatologic conditions (conditions in which the immune system attacks parts of the body). Nonprescription aspirin is used to reduce fever and to relieve mild to moderate pain from headaches, menstrual periods, arthritis, toothaches, and muscle aches. Nonprescription aspirin is also used to prevent heart attacks in people who have had a heart attack in the past or who have angina (chest pain that occurs when the heart does not get enough oxygen). Nonprescription aspirin is also used to reduce the risk of death in people who are experiencing or who have recently experienced a heart attack. Nonprescription aspirin is also used to prevent ischemic strokes (strokes that occur when a blood clot blocks the flow of blood to the brain) or mini-strokes (strokes that occur when the flow of blood to the brain is blocked for a short time) in people who have had this type of stroke or mini-stroke in the past. Aspirin will not prevent hemorrhagic strokes (strokes caused by bleeding in the brain). Aspirin is in a group of medications called salicylates. It works by stopping the production of certain natural substances that cause fever, pain, swelling, and blood clots.

• Aspirin is also available in combination with other medications such as antacids, pain relievers, and cough and cold medications. This monograph only includes information about the use of aspirin alone. If you are taking a combination product, read the information on the package or prescription label or ask your doctor or pharmacist for more information.

Spironolactone Overview

• Spironolactone is used to treat certain patients with hyperaldosteronism (the body produces too much aldosterone, a naturally occurring hormone); low potassium levels; heart failure; and in patients with edema (fluid retention) caused by various conditions, including liver, or kidney disease. It is also used alone or with other medications to treat high blood pressure. Spironolactone is in a class of medications called aldosterone receptor antagonists. It causes the kidneys to eliminate unneeded water and sodium from the body into the urine but reduces the loss of potassium from the body.

• 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:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

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.