Basic Information
ID DDInter1522 and DDInter314
Interaction Coadministration with probenecid may increase and prolong the serum concentrations of some cephalosporins. The proposed mechanism is competitive inhibition of renal tubular secretion by probenecid.
Management Although probenecid has been used therapeutically to enhance serum levels of various beta-lactam antibiotics, the potential for increased adverse effects should be considered when probenecid is added to existing cephalosporin therapy, particularly when the latter is given at high dosages or to patients who are elderly or have renal dysfunction. Adjustment of the cephalosporin dosage may be required in accordance with the individual product labeling. For example, cefotaxime dosage should generally not exceed 6 grams/day when administered with probenecid. Probenecid reportedly does not affect the elimination of ceftazidime or ceftriaxone.
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J Clin Pharmacol 14 (1974): 604-11 [14] Brown G, Zemcov SJ, Clarke AM "Effect of probenecid on cefazolin serum concentrations." J Antimicrob Chemother 31 (1993): 1009-11 [15] Kercsmar CM, Stern RC, Reed MD, et al "Ceftazidime in cystic fibrosis: pharmacokinetics and therapeutic response." J Antimicrob Chemother 12 (1983): 289-95 [16] Pitkin D, Dubb J, Actor P, et al "Kinetics and renal handling of cefonicid." Clin Pharmacol Ther 30 (1981): 587-93 [17] LeBel M, Paone RP, Lewis GP "Effect of probenecid on the pharmacokinetics of ceftizoxime." J Antimicrob Chemother 12 (1983): 147-55 [18] Spina SP, Dillon EC "Effect of chronic probenecid therapy on cefazolin serum concentrations." Ann Pharmacother 37 (2003): 621-4 [19] Nooyen SM, Overbeek BP, Delariviere AB, Storm AJ, Langemeyer JJ "Prospective randomised comparison of single-dose versus multiple-dose cefuroxime for prophylaxis in coronary artery bypass grafting." Eur J Clin Microbiol Infect Dis 13 (1994): 1033-7 [20] Griffith RS, Black HR, Brier GL, Wolny JD "Effect of probenecid on the blood levels and urinary excretion of cefamandole." Antimicrob Agents Chemother 11 (1977): 809-12 [21] Welling PG, Dean S, Selen A, et al "Probenecid: an unexplained effect on cephalosporin pharmacology." Br J Clin Pharmacol 8 (1979): 491-5 [22] "Product Information. Ceftin (cefuroxime)." Glaxo Wellcome, Research Triangle Park, NC. [23] Ings RM, Reeves DS, White LO, et al "The human pharmacokinetics of cefotaxime and its metabolites and the role of renal tubular secretion on their elimination." J Pharmacokinet Biopharm 13 (1985): 121-42 [24] "Product Information. Tazicef (ceftazidime)." SmithKline Beecham, Philadelphia, PA. [25] Vlasses PH, Holbrook AM, Schrogie JJ, Rogers JD, Ferguson RK, Abrams WB "Effect of orally administered probenecid on the pharmacokinetics of cefoxitin." 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Pharmacotherapy 24 (2004): 1784-92 [32] Schiff D, Drislane FW "Rapid-onset colchicine myoneuropathy." Arthritis Rheum 35 (1992): 1535-6 [33] Putterman C, Ben-Chetrit E, Caraco Y, Levy M "Colchicine intoxication: clinical pharmacology, risk factors, features, and management." Semin Arthritis Rheum 21 (1991): 143-55 [34] "Product Information. Colcrys (colchicine)." AR Scientific Inc, Philadelphia, PA. [35] Hung IF, Wu AK, Cheng VC, et al. "Fatal interaction between clarithromycin and colchicine in patients with renal insufficiency: a retrospective study." Clin Infect Dis 41 (2005): 291-300 [36] Rollot F, Pajot O, Chauvelot-Moachon L, Nazal EM, Kelaidi C, Blanche P "Acute colchicine intoxication during clarithromycin administration." Ann Pharmacother 38 (2004): 2074-7 [37] Akdag I, Ersoy A, Kahvecioglu S, Gullulu M, Dilek K "Acute colchicine intoxication during clarithromycin administration in patients with chronic renal failure." 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Alternative for Probenecid M04A
Lesinurad Febuxostat Pegloticase Colchicine Sulfinpyrazone Rasburicase

G01A
Tinidazole Ascorbic acid Hydroflumethiazide Chlorothiazide Simeprevir
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Alternative for Cefazolin J01D
Ceftriaxone Ceftazidime Aztreonam Cefiderocol
Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.