Probenecid with allopurinol

Patients with recurrent attacks, evidence of tophi or joint destruction, or uric acid nephrolithiasis are candidates for maintenance therapy with allopurinol or probenecid to lower serum uric add levels. 

When chemotherapeutic mercaptopurines (eg, azathioprine) are given concomitantly with allopurinol, their dosage must be reduced by about 75%. Allopurinol may also increase the effect of cyclophosphamide. Allopurinol inhibits the metabolism of probenecid and oral anticoagulants... 

Aspirin, salicylates, and thiazide diuretics should not be used with allopurinol. The dose of mercaptopurine should be reduced one-third or one-fourth when used with allopurinol. Acute poisoning of colchicine should be treated with gastric lavage and activated charcoal administration. Supportive maintenance measures for blood pressure and respiration should be provided. Probenecid is used by athletes to inhibit the urinary excretion of banned anabolic steroids.85... 

Side effects of these two drugs include nausea, skin rash, stomach upset or headaches. A drawback to the use of probenecid or sulfinpyrazone is that because of increased excretion of other organic acids that use the same transport system, the urine becomes more acidic than normal. Acidic urine may encourage the precipitation of uric acid and the formation of kidney stones. To avoid this patients should be treated with allopurinol first. Sulfinpyrazone enhances the effects of warfarin. 

Gout is an inflammatory joint disease caused by deposition of uric acid crystals in the joints. Treatment of gout aims to control acute attacks with analgesics and colchicine and in the longer term to reduce circulating uric acid levels either by inhibiting its production with allopurinol or by encouraging its excretion by the kidneys with probenecid or sulfinpyrazone. 

Antigout drugs No expected interaction with allopurinol, colchicine, or probenecid No expected interaction with allopurinol... 

Probenecid and benzbromarone increase the renal excretion of oxipurinol, the active metabolite of allopurinol, but this probably does not alter clinical efficacy. Theoretically, the use of uricosuric drugs with allopurinol could lead to uric acid precipitation in the kidneys and therefore maintenance of a high urine output is recommended when allopurinol is given by injection. Probenecid markedly increases the serum levels of allopurinol riboside, which may be advantageous in some circumstances. 

Gout is one of the most ancient diseases its clinical characteristics have been known for at least 2000 years. It is now very effectively treated with drugs that decrease production of uric acid by inhibition of the enzyme xanthine oxidase in purine degradation (Figure 10.9) (allopurinol), and a drug that increases the excretion of uric acid (probenecid)... 

Probenecid has been reported to inhibit renal elimination of many drugs acyclovir (325,326), allopurinol (327), bumetanide (328), cephalosporins (329-334), cidofovir (335), ciprofloxacin (336), famotidine (337), fexofenadine (338), furosemide (339), and oseltamivir (Ro 64-0802) (340). Recent studies have elucidated that probenecid is a potent inhibitor of renal organic anion transporters (OAT1 and OAT3) with the Ki values lower than the unbound plasma concentration of probenecid, indicating the interaction with probenecid includes inhibition of the basolateral uptake process mediated by OAT1 and/or OAT3. 

Prophylaxis Prophylactic treatment of patients with uric acid-lowering agents such as allopurinol or probenecid should not be started until the acute attack resolves. This is because these agents cause mobilization of urate crystals and may prolong the acute attack. Patients may need long-... 

Agents used to treat acute gout attacks as well as to prevent recurrent attacks should be used with caution in patients with hypertension and renal impairment. Doses may need to be adjusted in patients with decreased renal function. Probenecid is usually recommended for patients who are under 60 years of age, who have normal renal function, are diagnosed as an underexcreter, and have no history of kidney stones. Probenecid causes a marked increase of uric acid in the urine, and decreased renal elimination places the patient at risk for stone formation. Allopurinol is a good choice for patients with uric acid stones or renal insufficiency, as well as for those who are known to be overproducers of uric acid. 

C This patient is a candidate for allopurinol. Allopurinol is the drug of choice for patients with renal impairment. Probenecid is not recommended for patients with a CrCI rate of less than 50 mL/min. Indomethacin, ibuprofen, and colchicine are agents to treat acute gouty attacks. 

In a cost-effectiveness analysis in patients with nontophaceous recurrent gouty arthritis, urate-lowering therapy was found to reduce costs if patients experienced two or more recurrent attacks per year. Generic allopurinol was associated with a lower incremental cost-effectiveness ratio than were either probenecid or sulfinpyrazone. 

The investigation was conducted with the voluntary cooperation of 10 normal males (mean age, 33 years) who were placed on an essentially purine-free diet during the study. Renal handling of uric acid was examined by means of the pyrazinamide (PZA) and probenecid (PB) tests, performed in three uricemia states normouricemia 3.6 to 6.4 mg/dl), allopurinol-induced hypouricemia (under 3.5 mg/dl), and hyperuricemia after oral administration of RNA monosodium salt (over 6.5 mg/dl). 

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