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Drug Interactions between ampicillin / probenecid and grepafloxacin

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

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Interactions between your drugs

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 (6)
  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
Minor

probenecid grepafloxacin

Applies to: ampicillin / probenecid and grepafloxacin

Probenecid has been shown to interfere with the urinary excretion of certain quinolone antibiotics, resulting in increased plasma quinolone concentrations in some cases. The clinical relevance of this interaction is unknown but may be greater for quinolones that undergo significant tubular secretion via the renal anion transporter system such as cinoxacin, ciprofloxacin, enoxacin, gemifloxacin, nalidixic acid, and norfloxacin. In one study, serum levels of cinoxacin reportedly doubled in the presence of probenecid, while urinary recovery in a 7-hour period was reduced by 32%. In another study (n=12), mean systemic exposure (AUC) of a 200 mg IV dose of ciprofloxacin increased by 75% and renal clearance decreased by 64% following pretreatment with multiple-dose probenecid. Likewise, probenecid has been found to reduce renal clearance of enoxacin and gemifloxacin by approximately 50%. Another study reported a threefold increase in the peak serum nalidixic acid level of two volunteers 8 hours following coadministration of a 500 mg dose of nalidixic acid and a 500 mg dose of probenecid. Also, a 1 gram dose of probenecid reduced the 12-hour urinary recovery of a single 200 mg dose of norfloxacin by about one-half in five study subjects, although serum concentrations were not significantly changed. In contrast, probenecid appears to have no clinically significant effect on the pharmacokinetics of moxifloxacin, ofloxacin, or sparfloxacin. In general, no precautions appear to be necessary during coadministration of most quinolones and probenecid. However, in the treatment of urinary tract infections, clinicians should consider the possibility of reduced antibacterial efficacy due to decreased quinolone excretion into the urine.

References (11)
  1. Wijnands WJ, Vree TB, Baars AM, van Herwaarden CL (1988) "Pharmacokinetics of enoxacin and its penetration into bronchial secretions and lung tissue." J Antimicrob Chemother, 21, p. 67-77
  2. Shimada J, Yamaji T, Ueda Y, Uchida H, Kusajma H, Irikura T (1983) "Mechanism of renal excretion of AM-715, a new quinolonecarboxylic acid derivative, in rabbits, dogs, and humans." Antimicrob Agents Chemother, 23, p. 1-7
  3. Weidekamm E, Portmann R, Suter K, et al. (1987) "Single- and multiple-dose pharmacokinetics of fleroxacin, a trifluorinated quinolone, in humans." Antimicrob Agents Chemother, 31, p. 1909-14
  4. Rodriguez N, Madsen PO, Welling PG (1979) "Influence of probenecid on serum levels and urinary excretion of cinoxacin." Antimicrob Agents Chemother, 15, p. 465-9
  5. (2001) "Product Information. Noroxin (norfloxacin)." Merck & Co., Inc
  6. Dash H, Mills J (1976) "Letter: Severe metabolic acidosis associated with nalidixic acid overdose." Ann Intern Med, 84, p. 570-1
  7. Jaehde U, Sorgel F, Reiter A, Sigl G, Naber KG, Schunack W (1995) "Effect of probenecid on the distribution and elimination of ciprofloxacin in humans." Clin Pharmacol Ther, 58, p. 532-41
  8. Shimada J, Nogita T, Ishibashi Y (1993) "Clinical pharmacokinetics of sparfloxacin." Clin Pharmacokinet, 25, p. 358-69
  9. Nataraj B, Mamidi NVSR, Krishna DR (1998) "Probenecid affects the pharmacokinetics of ofloxacin in healthy volunteers." Clin Drug Invest, 16, p. 259-62
  10. Stass H, Sachse R (2001) "Effect of probenecid on the kinetics of a single oral 400mg dose of moxifloxacin in healthy male volunteers." Clin Pharmacokinet, 40 Suppl 1, p. 71-6
  11. (2003) "Product Information. Factive (gemifloxacin)." *GeneSoft Inc

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 (6)
  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

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.

Further information

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