Drug Interaction Report

GENERALLY AVOID: Probenecid is known to inhibit the renal transport of many organic compounds, including aminohippuric acid, and may affect the renal excretion of phenylacetylglutamine and hippurate, the byproducts formed when sodium phenylacetate and sodium benzoate are administered for the treatment of acute hyperammonemia in patients with urea cycle disorders. Since phenylacetylglutamine and hippurate serve as vehicles to reduce waste nitrogen levels in such patients, adequate renal excretion is necessary to treat hyperammonemia and reduce the risk of glutamine-induced neurotoxicity.

MANAGEMENT: Although the interaction is theoretical and no data are available, it may be appropriate to avoid using probenecid during treatment of acute hyperammonemia in patients with urea cycle disorders due to the urgent nature of the condition. Uncontrolled hyperammonemia can rapidly result in brain damage or death.

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.

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.