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 probenecid. 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. probenecid 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 (see warnings ). 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.

d 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. colchicine has been reported to adversely affect spermatogenesis in animals. reversible azoospermia has been reported in one patient.

robenecid or this drug combination. since colchicine 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.

or less. gastric intolerance may be indicative of overdosage, and may be corrected by decreasing the dosage. as uric acid tends to crystallize out of an acid urine, a liberal fluid intake is recommended, as well as sufficient sodium bicarbonate (3 to 7.5 g daily) or potassium citrate (7.5 g daily) to maintain an alkaline urine (see precautions ). alkalization of the urine is recommended until the serum urate level returns to normal limits and tophaceous deposits disappear, i.e., during the period when urinary excretion of uric acid is at a high level. thereafter, alkalization of the urine and the usual restriction of purine-producing foods may be somewhat relaxed. probenecid and colchicine (or probenecid) should be continued at the dosage that will maintain normal serum urate levels. when acute attacks have been absent for six months or more and serum urate levels remain within normal limits, the daily dosage of probenecid and colchicine may be decreased by 1 tablet every six months. the maintenance dosage should not be reduced to the point where serum urate levels tend to rise.

n of dosage or discontinuance of the drug. central nervous system: peripheral neuritis. musculoskeletal: muscular weakness. gastrointestinal: nausea, vomiting, abdominal pain, or diarrhea may be particularly troublesome in the presence of peptic ulcer or spastic colon. hypersensitivity: urticaria. hematologic: aplastic anemia, agranulocytosis. integumentary: dermatitis, purpura, alopecia. at toxic doses, colchicine may cause severe diarrhea, generalized vascular damage, and renal damage with hematuria and oliguria.

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 probenecid. 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. probenecid 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 (see warnings ). 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.

ar reabsorption of phosphorus is inhibited in hypoparathyroid but not in euparathyroid individuals. probenecid does not influence plasma concentrations of salicylates, nor the excretion of streptomycin, chloramphenicol, chlortetracycline, oxytetracycline, or neomycin. the mode of action of colchicine in gout is unknown. it is not an analgesic, though it relieves pain in acute attacks of gout. it is not a uricosuric agent and will not prevent progression of gout to chronic gouty arthritis. it does have a prophylactic, suppressive effect that helps to reduce the incidence of acute attacks and to relieve the residual pain and mild discomfort that patients with gout occasionally feel. in man and certain other animals, colchicine can produce a temporary leukopenia that is followed by leukocytosis. colchicine has other pharmacologic actions in animals: it alters neuromuscular function, intensifies gastrointestinal activity by neurogenic stimulation, increases sensitivity to central depressants, heightens response to sympathomimetic compounds, depresses the respiratory center, constricts blood vessels, causes hypertension by central vasomotor stimulation, and lowers body temperature.