Drug Interaction Report

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.

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.

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.