How does probenecid treat gout?

Firstly, I need to amend that question. Because, professional rheumatology advice tells gout patients to work with their physician to agree how to manage gout. So the question should be, "how do patient and physician decide if they will use probenecid to treat gout?"

Anyway, whatever questions you have about probenecid, we must start with those professional guidelines. So here are the facts about probenecid from the ACR Guideline for Gout Management.

FitzGerald, J.D., Dalbeth, N., Mikuls, T., Brignardello‐Petersen, R., Guyatt, G., Abeles, A.M., Gelber, A.C., Harrold, L.R., Khanna, D., King, C. and Levy, G., 2020. 2020 American College of Rheumatology guideline for the management of gout. Arthritis Care & Research, 72(6), pp.744-760.

Unfortunately, there are at least 3 versions of this document. So, for the avoidance of doubt, I use https://doi.org/10.1002/acr.24180. Including the errors corrected at https://doi.org/10.1002/acr.24566 and at https://doi.org/10.1002/acr.24401.

Probenecid Recommendations for Gout

Remember, the guideline stems from in-depth reviews of hundreds of gout studies. So I have not attempted to include every study that mentions probenecid. Because the main recommendations give suitable guidance for most patient-physician teams. Then, individual teams might consider further research that accounts for their particular nonstandard conditions.

Probenecid & Symptom-free High Uric Acid

Table 1 recommendations give advice about deciding to introduce uric acid treatment. Which the guide describes as “Indications for pharmacologic urate-lowering therapy (ULT)”. So the guide conditionally recommends against starting probenecid if patients have never experienced gout flares. Because the studies show that only a small percentage of high uric acid patients without symptoms go on to suffer gout flares within 5 years. Leading the rheumatologists to consider that treatment is unlikely to justify costs and risks.

Conditional recommendations need you to carefully consider your own situation. Because risks of not starting probenecid depend on your unique circumstances. Which reinforces the recurring theme that management of gout can never be fixed for all patients. Especially as patient preferences must be considered in every individual plan.

For patients with asymptomatic hyperuricemia (SU >6.8 mg/dl with no prior gout flares or subcutaneous tophi), we conditionally recommend against initiating any pharmacologic ULT (allopurinol, febuxostat, probenecid) over initiation of pharmacologic ULT. [Note: in this version, the table text is displayed as an image]

In fact, this first recommendation applies to all uric acid treatment. But I include it as probenecid is included in the conditional recommendation. And also in the extensive supplementary evidence. Importantly, that supplementary evidence (“SUPPLEMENTARY APPENDIX 8: Evidence Report”) includes a comparison of probenecid with allopurinol… Patients who receive probenecid

• May not have a different probability of achieving serum urate levels <6 mg/dL than patients who receive allopurinol, up to 29 months; but we are very uncertain about this evidence
• May have a lower risk of experiencing serious adverse events (including cardiovascular events, stroke, coronary revascularization, and heart failure) than patients who receive allopurinol, up to 4 months
• May have a lower risk of all-cause mortality than patients who receive allopurinol, up to 4 months

Probenecid & Chronic Kidney Disease

Table 2 includes "We strongly recommend a xanthine oxidase inhibitor over probenecid for those with CKD stage >3." So individual patient needs would need to be exceptional to override that recommendation. Which requires consideration of the supporting evidence. As well as subsequent research.

The choice of either allopurinol or febuxostat over probenecid is strongly recommended for patients with moderate-to-severe CKD (stage ≥3).

Probenecid Dosage

Table 2 also includes "For probenecid, we conditionally recommend starting at a low dose (500 mg once or twice daily) with dose titration over starting at a higher dose." So this conditional recommendation might not apply to you. But again, if in doubt, check with the supplementary evidence and subsequent research. Starting treatment with low-dose probenecid (500 mg once to twice daily) with subsequent dose titration over starting at a higher dose is conditionally recommended.

Your Probenecid Guidelines

Now you see that rheumatologists expect you to explain your preferences about probenecid to your doctor. So I hope you understand your responsibilities as you consult health professionals about your probenecid needs. But if you need help preparing for that consultation, just ask using the feedback options.

Please tell me your probenecid story in the Gout Forum.

Before you ask about probenecid, it's best to read all three articles in my probenecid facts series. So these guidelines are the first step. Next, you can read Probenecid Side Effects Research Studies. Then Probenecid for Gout Comorbidities Research Studies.

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