Common Adverse Effects

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Probenecid is well tolerated. Approximately 2% of patients develop mild GI irritation. The risk is increased at higher doses, and caution should be used in those with a history of peptic ulcer. It is ineffective in patients with renal insufficiency and should be avoided in those with creatinine clearance of <50 mL/min. Mild hypersensitivity reactions may occur in 2-4% of patients; serious hypersensitivity is extremely rare. The appearance of a rash during the concurrent administration of probenecid and penicillin G presents the physician with an awkward diagnostic dilemma. Substantial overdosage with probenecid results in CNS stimulation, convulsions, and death from respiratory failure.

THERAPEUTIC USE Gout

Probenecid (benebmid, others) is marketed for oral administration. The starting dose is 250 mg twice daily, increasing over 1-2 weeks to 500-1000 mg twice daily. Probenecid increases urinary urate levels. Liberal fluid intake therefore should be maintained throughout therapy to minimize the risk of renal stones. Probenecid should not be used in gouty patients with nephrolithiasis or with overproduction of uric acid. Concomitant colchicine or NSAIDs are indicated early in the course of therapy to avoid precipitating an attack of gout, which may occur in up to 20% of gouty patients treated with probenecid alone.

Combination with Penicillin

Probenecid was developed for the purpose of delaying the excretion of penicillin, and it still is used as an adjuvant to prolong penicillin concentrations in patients being treated for specific infections (e.g., syphilis) or in cases where penicillin resistance may be an issue (see Chapter 44).

Benzbromarone

This potent uricosuric agent is used in Europe. It is a potent and reversible inhibitor of the urate-anion exchanger in the proximal tubule. As the micronized powder, it is effective in a single daily dose of 40-80 mg. It is effective in patients with renal insufficiency and may be useful clinically in patients who are either allergic or refractory to other drugs used for the treatment of gout. Preparations that combine allopurinol and benzbromarone lower serum uric acid levels more effectively than either drug alone, despite the fact that benzbromarone lowers plasma levels of oxypurinol, the active metabolite of allopurinol.

For a complete Bibliographical listing see Goodman & Gilman's The Pharmacological Basis of Therapeutics, 11th ed., or Goodman & Gilman Online at www.accessmedicine.com.

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