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Drug Interactions between cefmetazole and probenecid

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

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Interactions between your drugs

Moderate

probenecid cefmetazole

Applies to: probenecid and cefmetazole

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

cefmetazole food

Applies to: cefmetazole

GENERALLY AVOID: Some cephalosporins may occasionally induce a disulfiram-like reaction when coadministered with alcohol. The interaction has been reported for cefamandole, cefoperazone, cefotetan, and moxalactam. These agents contain an N-methylthiotetrazole (NMTT) side chain that may inhibit aldehyde dehydrogenase (ALDH) similar to disulfiram. Following ingestion of alcohol, inhibition of ALDH results in increased concentration of acetaldehyde, the accumulation of which produces an unpleasant physiologic response referred to as the 'disulfiram reaction'. Symptoms include flushing, throbbing in head and neck, throbbing headache, respiratory difficulty, nausea, vomiting, sweating, thirst, chest pain, palpitation, dyspnea, hyperventilation, tachycardia, hypotension, syncope, weakness, vertigo, blurred vision, and confusion. Severe reactions may result in respiratory depression, cardiovascular collapse, arrhythmias, myocardial infarction, acute congestive heart failure, unconsciousness, convulsions, and death. Cefonicid contains a structurally similar side chain but did not produce elevations in blood acetaldehyde or a disulfiram reaction to ethanol in 15 healthy volunteers given single and multiple one gram doses of the drug.

MANAGEMENT: Patients receiving cephalosporins with the NMTT side chain should avoid the concomitant use of alcohol and alcohol-containing products.

References

  1. Kline SS, Mauro VF, Forney RB Jr, et al. (1987) "Cefotetan-induced disulfiram-type reactions and hypoprothrombinemia." Antimicrob Agents Chemother, 31, p. 1328-31
  2. Freundt KJ, Kitson TM (1986) "Inactivation of aldehyde dehydrogenase by a putative metabolite of cefamandole." Infection, 14, p. 44-7
  3. Freundt KJ, Schreiner E, Christmann-Kleiss U (1985) "Cefamandole: a competitive inhibitor of aldehyde dehydrogenase." Infection, 13, p. 91
  4. McMahon FG (1980) "Disulfiram-like reaction to a cephalosporin." JAMA, 243, p. 2397
  5. Reeves DS, Davies AJ (1980) "Antabuse effect with cephalosporins." Lancet, 2, p. 540
  6. Brown KR, Guglielmo BJ, Pons VG, Jacobs RA (1982) "Theophylline elixir, moxalactam, and a disulfiram reaction." Ann Intern Med, 97, p. 621-2
  7. Umeda S, Arai T (1985) "Disulfiram-like reaction to moxalactam after celiac plexus alcohol block." Anesth Analg, 64, p. 377
  8. Foster TS, Raehl CL, Wilson HD (1980) "Disulfiram-like reaction associated with a parenteral cephalosporin." Am J Hosp Pharm, 37, p. 858-9
  9. McMahon FG, Ryan JR, Jain AK, LaCorte W, Ginzler F (1987) "Absence of disulfiram-type reactions to single and multiple doses of cefonicid: a placebo-controlled study." J Antimicrob Chemother, 20, p. 913-8
View all 9 references

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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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