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Exacerbation of gout following therapy with probenecid may occur; in such cases colchicine or other appropriate therapy is advisable.
Probenecid increases plasma concentration of methotrexate in both animal and human. If probenecid is given with methotrexate, the dosage of methotrexate should be reduced and serum level may need to be monitored.
In patients on probenecid, 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 paradoxical effect.
The appearance of hypersensitivity reactions requires cessation of therapy with probenecid. Because of its mechanism of action, probenecid is not recommended in conjunction with a penicillin in the presence of known renal impairment.
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