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Drug Interactions between ampicillin / probenecid and cefaclor

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

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Interactions between your drugs

Moderate

probenecid cefaclor

Applies to: ampicillin / probenecid and cefaclor

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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Minor

ampicillin probenecid

Applies to: ampicillin / probenecid and ampicillin / probenecid

Probenecid may increase the plasma concentrations and half-lives of penicillins. The mechanism is competitive inhibition by probenecid of the renal tubular secretion of penicillins. While this interaction is often exploited to enhance the antibacterial effect of penicillins, toxicity may occur and should be considered if high penicillin dosages are administered intravenously.

References

  1. Sommers DK, Schoeman HS (1987) "Drug interactions with urate excretion in man?" Eur J Clin Pharmacol, 32, p. 499-502
  2. Waller ES, Sharanevych MA, Yakatan GJ (1982) "The effect of probenecid on nafcillin disposition." J Clin Pharmacol, 22, p. 482-9
  3. Shanson DC, McNabb R, Hajipieris P (1984) "The effect of probenecid on serum amoxycillin concentrations up to 18 hours after a single 3g oral dose of amoxycillin: possible implications for preventing endocarditis." J Antimicrob Chemother, 13, p. 629-32
  4. Sutherland R, Croydon EA, Rolinson GN (1972) "Amoxycillin: a new semi-synthetic penicillin." Br Med J, 3, p. 13-6
  5. Allen MB, Fitzpatrick RW, Barratt A, Cole RB (1990) "The use of probenecid to increase the serum amoxycillin levels in patients with bronchiectasis." Respir Med, 84, p. 143-6
  6. Gibaldi M, Schwartz MA (1968) "Apparent effect of probenecid on the distribution of penicillins in man." Clin Pharmacol Ther, 9, p. 345-9
View all 6 references

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Drug and food interactions

Moderate

ampicillin food

Applies to: ampicillin / probenecid

ADJUST DOSING INTERVAL: Certain penicillins may exhibit reduced gastrointestinal absorption in the presence of food. The therapeutic effect of the antimicrobial may be reduced.

MANAGEMENT: The interacting penicillin should be administered one hour before or two hours after meals. Penicillin V and amoxicillin are not affected by food and may be given without regard to meals.

References

  1. Neu HC (1974) "Antimicrobial activity and human pharmacology of amoxicillin." J Infect Dis, 129, s123-31
  2. Welling PG, Huang H, Koch PA, Madsen PO (1977) "Bioavailability of ampicillin and amoxicillin in fasted and nonfasted subjects." J Pharm Sci, 66, p. 549-52
  3. McCarthy CG, Finland M (1960) "Absorption and excretion of four penicillins." N Engl J Med, 263, p. 315-26
  4. Cronk GA, Wheatley WB, Fellers GF, Albright H (1960) "The relationship of food intake to the absorption of potassium alpha-phenoxyethyl penicillin and potassium phenoxymethyl penicillin from the gastrointestinal tract." Am J Med Sci, 240, p. 219-25
  5. Klein JO, Sabath LD, Finland M (1963) "Laboratory studies on oxacillin. I: in vitro activity against staphylococci and some other bacterial pathogens. II: absorption and urinary excretion in normal young." Am J Med Sci, 245, p. 399-411
  6. Neuvonen PJ, Elonen E, Pentikainen PJ (1977) "Comparative effect of food on absorption of ampicillin and pivampicillin." J Int Med Res, 5, p. 71-6
View all 6 references

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Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Beta-lactam antibiotics

Therapeutic duplication

The recommended maximum number of medicines in the 'beta-lactam antibiotics' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'beta-lactam antibiotics' category:

  • ampicillin/probenecid
  • cefaclor

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

See also

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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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer