ProbenecidRx

Trade Names: Benemid

Drug Class: Uricosuric

Preparations: 500-mg tablet

Dose: Initially, 250 mg twice daily for the first week, then increase to 500 mg twice daily, and, if needed, to a maintenance dose of 1–2 g/day in divided doses

Indications: To treat hyperuricemia associated with gout in patients who excrete <700 mg of urate in a 24-hour urine collection have normal renal function, no tophi, no history of renal calculi and do not have renal impairment.

Mechanism of Action: Inhibits renal tubular reabsorption of uric acid

Contraindications: Hypersensitivity to probenecid, renal impairment, nephrolithiasis.

Precautions: Use caution with peptic ulcer. It inhibits excretion of penicillins, and toxic levels may accumulate in patients with impaired renal function. Maintain good urine output to decrease risk of stones and consider urine alkalinization.

Monitoring: Monitor uric acid periodically

Pregnancy Risk: No FDA category on label, likely C

Adverse Effects
Common: Nausea, vomiting, headache
Less common: Rash, itch, allergy, precipitation of an acute attack of gout, leukopenia, aplastic anemia, urate nephropathy, nephrotic syndrome

Drug Interactions
Salicylates (high dose): Antagonize uricosuric effect
Beta-lactams (penicillins, cephalosporins) and quinolones: Increased plasma levels of antibiotics
Methotrexate:  Increased MTX levels and toxicity
Antivirals: Reduced excretion of acyclovir and zidovudine

Patient Instructions: Drink plenty of fluids. Avoid aspirin or other salicylates (may antagonize the uricosuric effect).

Comments: To prevent acute attacks of gout, chronic colchicine or NSAID therapy is coadministered for the first 3–12 months of probenecid therapy. In patients with tophi or renal stones, allopurinol is preferred.

Clinical Pharmacology: Rapid, complete absorption; hepatic metabolism and renal excretion. Half-life is 6–12 hours.

Cost: $

BIBLIOGRAPHY

Terkeltaub RA. Clinical practice. Gout. N Engl J Med 2003;349:1647–1655.PMID: 14573737

Khanna D, Fitzgerald JD, Khanna PP et al. 2012 American College of Rheumatology guidelines for management of gout. Arthritis Care Res 2012;64:1431-46.PMID:23024028