Probenecid and Colchicine
Probenecid increases plasma concentrations of methotrexate in both animals and humans. In animal studies, increased methotrexate toxicity has been reported. If probenecid and colchicine is given with methotrexate, the dosage of methotrexate should be reduced and serum levels may need to be monitored.
In patients on probenecid and colchicine the use of salicylates in either small or large doses is contraindicated because it antagonizes the uricosuric action of probenecid. The biphasic action of salicylates in the renal tubules accounts for the so-called "paradoxical effect" of uricosuric agents. In patients on probenecid and colchicine who require a mild analgesic agent the use of acetaminophen rather than small doses of salicylates would be preferred.
Rarely, severe allergic reactions and anaphylaxis have been reported with the use of probenecid and colchicine. Most of these have been reported to occur within several hours after readministration following prior usage of the drug.
The appearance of hypersensitivity reactions requires cessation of therapy with probenecid and colchicine.
Hematuria, renal colic, costovertebral pain, and formation of uric acid stones associated with the use of probenecid and colchicine in gouty patients may be prevented by alkalization of the urine and a liberal fluid intake (see DOSAGE AND ADMlNlSTRATION). In these cases when alkali is administered, the acid-base balance of the patient should be watched.
Use with caution in patients with a history of peptic ulcer.
Probenecid and colchicines has been used in patients with some renal impairment but dosage requirements may be increased. Probenecid and colchicine may not be effective in chronic renal insufficiency particularly when the glomerular filtration rate is 30 mL/minute or less.
A reducing substance may appear in the urine of patients receiving probenecid. This disappears with discontinuance of therapy. Suspected glycosuria should be confirmed by using a test specific for glucose.
Adequate animal studies have not been conducted to determine the carcinogenicity potential of probenecid or this drug combination. Since colchicines is an established mutagen, its ability to act as a carcinogen must be suspected and administration of probenecid and colchicine should involve a weighing of the benefit-vs-risk when long-term administration is contemplated.
Last reviewed on RxList: 9/29/2008
This monograph has been modified to include the generic and brand name in many instances.
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