Trichlormethiazide and Ketorolac Ophthalmic: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Trichlormethiazide
No brand names on recordKetorolac Ophthalmic
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 and possible nephrotoxicity
Interaction Deep Dive
Risk of renal toxicity is increased with combined use of NSAIDs and diuretics due to NSAID-associated dose-dependent reduction in prostaglandin formation and in renal blood flow. Coadministration of NSAIDs and thiazide diuretics has reduced the natriuretic effect of the diuretic in some patients, also related to the effect of NSAID inhibition of renal prostaglandin synthesis2. 9. During concomitant use of NSAIDs and diuretics, monitor for signs of worsening renal function and assure diuretic efficacy, including appropriate effects on blood pressure 231.
Why it happens (mechanism)
Decreased renal prostaglandin production
Literature reports
5 reports — tap to read
a) NSAIDs may increase blood pressure and antagonize the effects of antihypertensive agents. They can cause salt and water retention and increase the extracellular volume. NSAIDs also cause a decrease in prostaglandin synthesis in blood vessel walls, which removes a direct vasodilatory influence and also increases the vascular response to vasoconstrictor stimuli. The antagonism of the hypotensive effect of diuretics is probably due to NSAID-induced inhibition of prostaglandin synthesis. NSAIDs also have independent and opposing actions on the various physiological mechanisms that regulate blood pressure 5.
b) The effect of tenidap 120 mg on the hypotensive efficacy of hydroCHLOROthiazide or bendrofluazide was assessed in 23 patients with controlled mild to moderate, uncomplicated, essential hypertension. Blood pressure increased marginally, and the increase in mean standing diastolic pressure observed with tenidap was significantly greater than the change in the placebo group 6.
c) The effect of a single dose challenge of naproxen (500 mg) and sulindac (200 mg) on renal function was studied in 5 volunteers, and the effect of a single dose challenge of hydrochlorothiazide (100 mg) on renal function when the diuretic was given alone or when superimposed on chronic therapy of either naproxen or sulindac. None of the NSAID or diuretic exposures significantly influenced the glomerular filtration rate, as measured by creatinine clearance. Over the first 4 hours of the study, both naproxen and sulindac reduced fractional excretion of sodium by approximately 50%. Concurrent hydroCHLOROthiazide and sulindac therapy resulted in a blunting of the natriuresis by approximately 30% compared with when the diuretic was given alone. The action of the diuretic was unchanged by naproxen 7.
d) Administration of indomethacin 25 mg 3 times daily in young healthy adults did not alter the pharmacokinetics of hydroCHLOROthiazide, but caused an increase in body weight and plasma potassium levels and a decrease in plasma renin activity 8. This evidence indirectly supports the hypothesis that the attenuation of diuretic action by indomethacin results from an alteration in hydroCHLOROthiazide pharmacodynamics.
e) 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 an NSAID resulted in a 3-fold increase over that for diuretic use only 4.
Common questions
Can I take Trichlormethiazide and Ketorolac Ophthalmic together?
Reduced diuretic effectiveness and possible nephrotoxicity Always confirm with your pharmacist or prescriber before making any change.
How serious is the Trichlormethiazide and Ketorolac Ophthalmic interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Trichlormethiazide or Ketorolac Ophthalmic 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 (9)
- Product Information: CALDOLOR(R) intravenous injection, ibuprofen intravenous injection. Cumberland Pharmaceuticals Inc. (per FDA), Nashville, TN, 2016. DailyMed
- Product Information: DAYPRO(R) oral caplets, oxaprozin oral caplets. GD Searle LLC (per FDA), New York, NY, 2016. DailyMed
- Product Information: ANAPROX(R) oral tablets, naproxen sodium oral tablets. Canton Laboratories, LLC (per FDA), Alpharetta, GA, 2016. DailyMed
- 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
- 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
- Rapeport WG, Grimwood VC, Korlipara K, et al: The effect of tenidap on the anti-hypertensive efficacy of thiazide diuretics in patients treated for mild to moderate hypertension. Br J Clin Pharmacol 1995; 39(suppl 1):51S-55S. PubMed
- Dixey JJ, Noormohamed FH, Lant AF, et al: The effects of naproxen and sulindac on renal function and their interaction with hydrochlorothiazide and piretanide in man. Br J Clin Pharmacol 1987; 23:55-63. DOI
- Koopmans PP, Kateman WG, Tan Y, et al: Effects of indomethacin and sulindac on hydrochlorothiazide kinetics. Clin Pharmacol Ther 1985; 37:625-628. PubMed
- Product Information: Diovan HCT oral tablets, valsartan hydrochlorothiazide oral tablets. Novartis Pharmaceuticals Corporation (per FDA), East Hanover, NJ, 2012. DailyMed
Keep reading about Trichlormethiazide
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