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.
Benemid 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 latter should be determined from time to time when a sulfonamide and probenecid and colchicine
are co-administered for prolonged periods. Benemid may prolong or enhance the action of oral sulfonylureas and
thereby increase the risk of hypoglycemia.
It has been reported that patients receiving probenecid require significantly less thiopental for induction of
anesthesia. In addition, ketamine and thiopental anesthesia were significantly prolonged in rats receiving
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. Although the clinical significance of this observation
has not been established, a lower dosage of the drug may be required to produce a therapeutic effect, and increases
in dosage of the drug in question should be made cautiously and in small increments when probenecid is being
co-administrated. Although specific instances of toxicity due to this potential interaction have not been observed to
date, physicians should be alert to this possibility.
Benemid given concomitantly with sulindac had only a slight effect on plasma sulfide levels, while plasma
levels of sulindac and sulfone were increased. Sulindac was shown to produce a modest reduction in the uricosuric
action of probenecid, which probably is not significant under most circumstances.
In animals and in humans, probenecid has been reported to increase plasma concentrations of methotrexate .
Falsely high readings for theophylline have been reported in an in vitro study, using the Schack and Waxler
technique, when therapeutic concentrations of theophylline and probenecid were added to human plasma.