Aspirin with Probenecid Interaction Details

Brand Names Associated with Aspirin

Brand Names Associated with Probenecid

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

Interaction Effect

Reversal of the uricosuric effects of the other drug

Interaction Summary

Avoid concomitant use of aspirin with uricosuric agents like probenecid[1]. Salicylates like aspirin antagonize the uricosuric action of probenecid [2]. High-dose salicylates have a uricosuric action. However, the use of high-dose aspirin may completely block the uricosuric effects of probenecid [3][4][5]. Conversely, the pharmacokinetics of nonsteroidal anti-inflammatory agents (NSAIDs) may be affected by probenecid. Probenecid is an inhibitor of organic acid transport in the kidney and other organs; therefore, it can inhibit both renal and biliary excretion of NSAIDs. In addition, it has been proposed that the decreased clearance may result in an increased concentration of the glucuronide metabolites which are in turn broken down by glucuronidases to release active NSAIDs [6][7][8]. Conversely, no adverse effect of aspirin 325 mg/day on serum urate concentrations or urinary urate clearance rates have also been demonstrated [9]. The clinical importance of this pharmacokinetic interaction remains to be determined.

Severity

Moderate

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Avoid concomitant use of aspirin with uricosuric agents like probenecid[1]. Salicylates like aspirin antagonize the uricosuric action of probenecid [2].

Mechanism Of Interaction

High-dose salicylates and probenecid each block the uricosuric effects of the other

Literature Reports

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 milligrams% were given concomitantly [3]. Conversely, the uricosuric effects of aspirin were reversed upon addition of probenecid to aspirin regimens.

B) In another study, uric acid clearance was reduced from 3162 mcg/minute while on probenecid to 1152 mcg/minute following a single 300 milligram dose of aspirin [10]. Thus, even small doses of aspirin appear to antagonize probenecid's uricosuric effects.

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 0.3-1.9) with a mean creatinine clearance of 89.8 mL/min (range 30-133). 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 enhanced in the aspirin 6 hour treatment arm (p = 0.036) compared to the aspirin given concomitantly with probenecid [9].

References

1 ) Product Information: CARISOPRODOL, ASPIRIN, CODEINE PHOSPHATE oral tablets, carisoprodol, aspirin, codeine phosphate oral tablets. Ingenus Pharmaceuticals LLC (per DailyMed), Orlando, FL, 2021.

2 ) Product Information: PERCODAN(R) oral tablets, oxycodone aspirin oral tablets. Endo Pharmaceuticals Inc. (per FDA), Malvern, PA, 2021.

3 ) 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.

4 ) Seegmiller JE & Grayzel AI: Use of newer uricosuric agents in the management of gout. JAMA 1960; 173:1076.

5 ) Brooks CD & Ulrich JE: Effect of ibuprofen or aspirin on probenecid-induced uricosuria. J Int Med Res 1980; 8:283-285.

6 ) Furst DE: Clinically important interactions of nonsteroidal antiinflammatory drugs with other medications. J Rheumatol Suppl 1988; 17:58-62.

7 ) Brouwers J & de Smet P: Pharmacokinetic-pharmacodynamic drug interactions with nonsteroidal anti-inflammatory drugs. Clin Pharmacokinet 1994; 2:462-485.

8 ) Johnson A, Seidemann P, & Day R: NSAID-related adverse drug interactions with clinical relevance. An update. Int J Clin Pharmacol Ther 1994; 32:509-532.

9 ) 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.

10 ) Diamond HS & Meisel AD: Postsecretory reabsorption of urate in man. Arthritis Rheum 1975; 18:805-809.

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.

Probenecid Overview

• Probenecid is used to treat chronic gout and gouty arthritis. It is used to prevent attacks related to gout, not treat them once they occur. It acts on the kidneys to help the body eliminate uric acid. Probenecid is also used to make certain antibiotics more effective by preventing the body from passing them in the urine.

• This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.

Return To Our Drug Interaction Homepage

Feedback, Question Or Comment About This Information?

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.