Probenecid
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Dosing and administration[2]
Uricosuric agent. Ensure high fluid intake and consider urine alkalinisation early to reduce urate stone risk. Less effective as renal function declines. Co-prescribe flare prophylaxis on initiation.
| Indication | Starting dose | Titration and maximum |
|---|---|---|
| Gout (urate lowering) | 250 mg twice daily for 1 week, then 500 mg twice daily. | May increase by 500 mg every 4 weeks to a maximum of 2 g/day, titrating to a serum urate target. Ineffective when creatinine clearance is below about 30 mL/min. |
Renal adjustment. Reduced efficacy in renal impairment and generally not used below a creatinine clearance of about 30 mL/min.
Monitoring
- Serum urate to guide titration.
- Adequate hydration and early urine alkalinisation to reduce urate stone risk.
Contraindications
- Known uric acid kidney stones.
- Blood dyscrasias.
- Do not start during an acute flare.
Key interactions
- Raises levels of penicillins, methotrexate (increased toxicity), and other renally secreted drugs.
- Salicylates antagonise the uricosuric effect; avoid.
Clinical notes
How it is used in gout
Uricosuric agent. A xanthine oxidase inhibitor is strongly preferred over probenecid in CKD stage 3 or worse, so probenecid is generally reserved for patients with preserved renal function or intolerance to xanthine oxidase inhibitors.[1]
Monitoring
Serial serum urate to titrate to target. Checking urinary uric acid before starting a uricosuric is conditionally recommended against, and alkalinizing the urine during uricosuric treatment is conditionally recommended against.[1]
Common effects
Background clinical knowledge (not from the guideline): gastrointestinal upset, rash, and flare on initiation.
Important cautions
Background and monograph, not from the gout guideline: reduced efficacy in renal impairment; caution with a history of urolithiasis; probenecid reduces renal excretion of several drugs (numerous interactions). Reconcile dosing, renal thresholds, and interactions with the product monograph.
References
- FitzGerald JD, Dalbeth N, Mikuls T, et al. 2020 American College of Rheumatology Guideline for the Management of Gout. Arthritis Care Res (Hoboken). 2020;72(6):744-760. doi:10.1002/acr.24180 https://doi.org/10.1002/acr.24180
- Probenecid tablets Product Monograph. Health Canada authorized product monograph. https://health-products.canada.ca/dpd-bdpp/