Mesalamine Rectal and Probenecid: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Probenecid
No brand names on recordMesalamine Rectal
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
Salicylates antagonize the uricosuric effects of probenecid
Interaction Deep Dive
The use of probenecid and salicylates in either small or large doses is contraindicated because salicylates antagonize the uricosuric action of probenecid. In patients on probenecid who require a mild analgesic agent the use of acetaminophen rather than small doses of salicylates would be preferred. The biphasic action of salicylates in the renal tubules accounts for the so-called "paradoxical effect" of uricosuric agents1. High-dose salicylates have a uricosuric action. However, the use of high-dose aspirin may completely block the uricosuric effects of probenecid 2. Uric acid clearance is reduced following a single 300 mg dose of aspirin 3.
Why it happens (mechanism)
Salicylates antagonize the uricosuric effects of probenecid
Literature reports
3 reports — tap to read
a) Aspirin appears to antagonize the uricosuric effects of several agents that are used to enhance uric acid excretion, including probenecid. The uricosuric effect of probenecid was blocked when doses of aspirin producing serum salicylate levels greater than 5 mg were given concomitantly 2.
b) In another study, uric acid clearance was reduced from 3162 mcg/min while on probenecid to 1152 mcg/min following a single 300 mg dose of aspirin 3.
c) A crossover study involving eleven patients determined that low dose daily enteric coated aspirin does not significantly interfere with the uricosuric effects of probenecid in patients with gouty arthritis. The patients were taking stable doses of probenecid with the mean dose being 500 mg twice daily (range, 500 to 1500 mg daily). Patients received enteric coated aspirin 325 mg each morning along with probenecid on days 1 through 14. On days 15 through 28, aspirin was administered 6 hours after the morning dose of probenecid. Mean serum creatinine was 0.97 mg/dL (range, 0.3 to 1.9) with a mean creatinine clearance of 89.8 mL/min (range, 30 to 133). There were no adverse effects to aspirin in either arm of the study. There was no statistical difference in serum uric acid level or total urinary uric acid excretion in either aspirin/probenecid treatment group compared to probenecid alone. When the two aspirin dosing schedules were evaluated, the urinary excretion was significantly enhanced in the aspirin 6 hour treatment arm compared to the aspirin given concomitantly with probenecid 4.
Common questions
Can I take Mesalamine Rectal and Probenecid together?
Salicylates antagonize the uricosuric effects of probenecid Always confirm with your pharmacist or prescriber before making any change.
How serious is the Mesalamine Rectal and Probenecid interaction?
It is rated contraindicated. These should generally not be used together.
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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Mesalamine Rectal or Probenecid 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 (4)
- Product Information: PROBENECID oral tablet, probenecid oral tablet. Lannett Company (per DailyMed), Philadelphia, PA, 2021. DailyMed
- Pascale L, Dubin A, Bronsky D, et al: Inhibition of the uricosuric action of Benemid by salicylate. J Lab Clin Med 1955; 45:771-777.
- Diamond HS & Meisel AD: Postsecretory reabsorption of urate in man. Arthritis Rheum 1975; 18:805-809. PubMed
- Harris M, Bryant L, Danaher P, et al: Effect of low dose daily aspirin on serum urate levels and urinary excretion in patients receiving probenecid for gouty arthritis. J Rheumatol 2000; 27:2873-2876.
Keep reading about Probenecid
Keep reading about Mesalamine Rectal
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