Spironolactone and Ketorolac Injection: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Spironolactone
Ketorolac Injection
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Reduced diuretic effectiveness, hyperkalemia, or possible nephrotoxicity
Interaction Deep Dive
Concomitant use of NSAIDs and diuretics may increase the risk of renal toxicity2. Severe hyperkalemia has been reported with use of NSAIDs 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 56. When concomitant use is necessary, monitor for signs of worsening renal function and assure diuretic efficacy, including appropriate effects on blood pressure 71. Consider monitoring serum potassium levels 8.
Why it happens (mechanism)
Reduced renal prostaglandin synthesis
Literature reports
5 reports — tap to read
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) 9.
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 3.
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 10.
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 4.
e) NSAIDs may negate the diuretic and antihypertensive effects of potassium-sparing diuretics 11. Acute reversible renal failure has been reported 121314. NSAIDs may cause hyperkalemia by inducing hyporeninemic hypoaldosteronism. Thus, additive effects on potassium homeostasis may occur 15.
Common questions
Can I take Spironolactone and Ketorolac Injection together?
Reduced diuretic effectiveness, hyperkalemia, or possible nephrotoxicity Always confirm with your pharmacist or prescriber before making any change.
How serious is the Spironolactone and Ketorolac Injection interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Spironolactone or Ketorolac Injection need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (15)
- Product Information: CALDOLOR(R) intravenous injection, ibuprofen intravenous injection. Cumberland Pharmaceuticals Inc. (per FDA), Nashville, TN, 2016. DailyMed
- Product Information: ANAPROX(R) oral tablets, naproxen sodium oral tablets. Canton Laboratories, LLC (per FDA), Alpharetta, GA, 2016. DailyMed
- 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. PubMed
- 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. DOI
- Product Information: Aldactazide® oral tablets, spironolactone hydrochlorothiazide oral tablets. Pfizer Labs (per FDA), New York, NY, 2025.
- Product Information: ALDACTONE® oral tablets, spironolactone oral tablets. Pfizer Labs (per FDA), New York, New York, 2025. DailyMed
- Product Information: MOBIC(R) oral tablets, oral suspension, meloxicam oral tablets, oral suspension. Boehringer Ingelheim Pharmaceuticals, Inc. (per FDA), Ridgefield, CT, 2016.
- Product Information: INSPRA(R) oral tablets, eplerenone oral tables. GD Searle (per FDA), New York, NY, 2016. DailyMed
- Ramsay L, Shelton J, Harrison I, et al: Spironolactone and potassium canrenoate in normal man. Clin Pharmacol Ther 1976; 20:167-177. PubMed
- Fairley KF, Woo KT, Birch DF, et al: Triamterene-induced crystalluria and cylinduria: clinical and experimental studies. Clin Nephrol 1986; 26:169-173.
- 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. PubMed
- Mathews A & Baillie FR: Acute renal failure and hyperkalaemia associated with triamterene and indomethacin. Vet Hum Toxicol 1986; 28:224-225.
- Favre L, Glasson P, & Vallotton MB: Reversible acute renal failure from combined triamterene and indomethacin. Ann Intern Med 1982; 96:317-320. DOI
- Weinberg MS, Quigg RJ, Salant DJ, et al: Anuric renal failure precipitated by indomethacin and triamterene. Nephron 1985; 40:216-218. DOI
- Mor R, Pitlik S, & Rosenfeld JB: Indomethacin- and Moduretic-induced hyperkalemia. Isr J Med Sci 1983; 19:535-537.
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