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Drug Interactions between cefpodoxime and probenecid

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

probenecid cefpodoxime

Applies to: probenecid and cefpodoxime

MONITOR: 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, although data suggest other mechanisms may also be involved. The magnitude of interaction appears to be dependent on the dose and timing of administration of probenecid, with greater pharmacokinetic changes reported when larger doses of probenecid are used and when probenecid is administered with or immediately before cephalosporin administration. Increases of 30% to more than 100% in systemic exposure and half-life, and decreases of approximately 30% to 60% in clearance, have been reported for various cephalosporins studied.

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.

References

  1. Pitkin D, Dubb J, Actor P, et al. (1981) "Kinetics and renal handling of cefonicid." Clin Pharmacol Ther, 30, p. 587-93
  2. Luthy R, Blaser J, Bonetti A, Simmen H, Wise R, Siegenthaler W (1981) "Comparative multiple-dose pharmacokinetics of cefotaxime, moxalactam, and ceftazidime." Antimicrob Agents Chemother, 20, p. 567-75
  3. Kercsmar CM, Stern RC, Reed MD, et al. (1983) "Ceftazidime in cystic fibrosis: pharmacokinetics and therapeutic response." J Antimicrob Chemother, 12, p. 289-95
  4. Vlasses PH, Holbrook AM, Schrogie JJ, Rogers JD, Ferguson RK, Abrams WB (1980) "Effect of orally administered probenecid on the pharmacokinetics of cefoxitin." Antimicrob Agents Chemother, 17, p. 847-55
  5. Reeves DS, Bullock DW, Bywater MJ, Holt HA, White LO, Thornhill DP (1981) "The effect of probenecid on the pharmacokinetics and distribution of cefoxitin in healthy volunteers." Br J Clin Pharmacol, 11, p. 353-9
  6. LeBel M, Paone RP, Lewis GP (1983) "Effect of probenecid on the pharmacokinetics of ceftizoxime." J Antimicrob Chemother, 12, p. 147-55
  7. Stoeckel K, Trueb V, Dubach UC, McNamara PJ (1988) "Effect of probenecid on the elimination and protein binding of ceftriaxone." Eur J Clin Pharmacol, 34, p. 151-6
  8. Ko H, Cathcart KS, Griffith DL, Peters GR, Adams WJ (1989) "Pharmacokinetics of intravenously administered cefmetazole and cefoxitin and effects of probenecid on cefmetazole elimination." Antimicrob Agents Chemother, 33, p. 356-61
  9. Santoro J, Agarwal BN, Martinelli R, et al. (1978) "Pharmacology of cefaclor in normal volunteers and patients with renal failure." Antimicrob Agents Chemother, 13, p. 951-4
  10. Welling PG, Dean S, Selen A, et al. (1979) "Probenecid: an unexplained effect on cephalosporin pharmacology." Br J Clin Pharmacol, 8, p. 491-5
  11. Marino EL, Dominguez-Gil A (1981) "The pharmacokinetics of cefadroxil associated with probenecid." Int J Clin Pharmacol Ther Toxicol, 19, p. 506-8
  12. Mischler TW, Sugerman AA, Willard DA, et al. (1974) "Influence of probenecid and food on the bioavailability of cephradine in normal male subjects." J Clin Pharmacol, 14, p. 604-11
  13. Shukla UA, Pittman KA, Barbhaiya RH (1992) "Pharmacokinetic interactions of cefprozil with food, propantheline, metoclopramide, and probenecid in healthy volunteers." J Clin Pharmacol, 32, p. 725-31
  14. Ings RM, Reeves DS, White LO, et al. (1985) "The human pharmacokinetics of cefotaxime and its metabolites and the role of renal tubular secretion on their elimination." J Pharmacokinet Biopharm, 13, p. 121-42
  15. Griffith RS, Black HR, Brier GL, Wolny JD (1977) "Effect of probenecid on the blood levels and urinary excretion of cefamandole." Antimicrob Agents Chemother, 11, p. 809-12
  16. Meister F, et al. (1986) "Reduction of ceftizoxime dosing interval by coadministration of probenecid." Clin Pharmacol Ther, 39, p. 210
  17. "Product Information. Vantin (cefpodoxime)." Pharmacia and Upjohn
  18. Ko H, Cathcart KS, Peters GR, Griffith DL, Adams WJ (1988) "Comparative single dose pharmacokinetics of cefmetazole and cefoxitin and the effects of probenecid on cefmetazole disposition in humans." Pharm Res, 5, s152
  19. (2002) "Product Information. Fortaz (ceftazidime)." Glaxo Wellcome
  20. (2002) "Product Information. Tazicef (ceftazidime)." SmithKline Beecham
  21. (2002) "Product Information. Rocephin (ceftriaxone)." Roche Laboratories
  22. (2002) "Product Information. Ceftin (cefuroxime)." Glaxo Wellcome
  23. Brown GR (1993) "Cephalosporin-probenecid drug interactions." Clin Pharmacokinet, 24, p. 289-300
  24. Brown G, Zemcov SJ, Clarke AM (1993) "Effect of probenecid on cefazolin serum concentrations." J Antimicrob Chemother, 31, p. 1009-11
  25. Nooyen SM, Overbeek BP, Delariviere AB, Storm AJ, Langemeyer JJ (1994) "Prospective randomised comparison of single-dose versus multiple-dose cefuroxime for prophylaxis in coronary artery bypass grafting." Eur J Clin Microbiol Infect Dis, 13, p. 1033-7
  26. (2001) "Product Information. Omnicef (cefdinir)." Parke-Davis
  27. Garton AM, Rennie RP, Gilpin J, Marrelli M, Shafran SD (1997) "Comparison of dose doubling with probenecid for sustaining serum cefuroxime levels." J Antimicrob Chemother, 40, p. 903-6
  28. Spina SP, Dillon EC (2003) "Effect of chronic probenecid therapy on cefazolin serum concentrations." Ann Pharmacother, 37, p. 621-4
View all 28 references

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Drug and food interactions

Moderate

cefpodoxime food

Applies to: cefpodoxime

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of cefpodoxime proxetil tablets. Following a 200 mg dose taken with food, the extent of absorption (mean AUC) was 21% to 33% higher and the mean peak plasma concentration (Cmax) 19% higher than under fasting conditions. Time to peak concentration (Tmax) was not significantly different between fed and fasted states. On the contrary, when a 200 mg dose of the suspension was taken with food, the mean AUC and Cmax were not significantly different than those under fasting conditions, although the rate of absorption was slower with food (48% increase in Tmax ).

MANAGEMENT: To ensure maximal oral absorption, cefpodoxime proxetil tablets should be administered with or immediately after a meal.

References

  1. Hughes GS, Heald DL, Barker KB, et al. (1989) "The effects of gastric pH and food on the pharmacokinetics of a new oral cephalosporin, cefpodoxime proxetil." Clin Pharmacol Ther, 46, p. 674-85
  2. "Product Information. Vantin (cefpodoxime)." Pharmacia and Upjohn
  3. Borin MT, Driver MR, Forbes KK (1995) "Effect of timing of food on absorption of cefpodoxime proxetil." J Clin Pharmacol, 35, p. 505-9

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

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