SW Probenecid Drug Interactions

When probenecid is used to elevate plasma concentrations of penicillin, or other beta-lactams, or when such drugs are given to patients taking probenecid therapeutically, high plasma concentrations of the other drug may increase the incidence of adverse reactions associated with that drug. In the case of penicillin, or other beta-lactams, psychic disturbances have been reported.
The use of salicylates antagonizes the uricosuric action of probenecid. The uricosuric action of probenecid is also antagonized by pyrazinamide.
Probenecid produces an insignificant increase in free sulfonamide plasma concentrations but a significant increase in total sulfonamide plasma levels. Since probenecid decreases the renal excretion of conjugated sulfonamides, plasma concentrations of the later should be determined from time to time when a sulfonamide and probenecid are coadministered for prolonged periods.
Probenecid may prolong or enhance the action of oral sulfonylureas and thereby increase the risk of hypoglycemia.
The concomitant administration of probenecid increases the mean plasma elimination half-life of a number of drugs which can lead to increased plasma concentrations. These include agents such as indomethacin, acetaminophen, naproxen, ketoprofen, meclofenamate, lorazepam, and rifampin. In animals and in humans, probenecid has been reported to increase plasma concentrations of methotrexate.