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Drug Interactions between levofloxacin and probenecid

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

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Interactions between your drugs

Minor

probenecid levoFLOXacin

Applies to: probenecid and levofloxacin

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

  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
View all 11 references

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Drug and food interactions

Moderate

levoFLOXacin food

Applies to: levofloxacin

ADJUST DOSING INTERVAL: Food may reduce the oral absorption and bioavailability of levofloxacin. According to the drug product labeling, administration of levofloxacin 500 mg with food prolonged the time to peak concentration by 1 hour and decreased the Cmax decreased by 25% following administration of the oral solution and by 14% following administration of the oral tablet.

MANAGEMENT: To ensure maximal and consistent oral absorption, levofloxacin oral solution should be taken at least one hour before or two hours after meals. For administration of the oral solution with continuous enteral nutrition, some experts recommend that the tube feeding should be interrupted for one hour before and two hours after the dose of levofloxacin. The oral tablets may be taken without regard to food.

References

  1. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT (2009) "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm, 66, p. 1438-67

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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.

Further information

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