Drug Interactions between ampicillin / probenecid and vadadustat

MONITOR: Coadministration with moderate or potent inhibitors of the uptake transporters organic anion transporter 1 and/or 3 (OAT1, OAT3) may increase the plasma concentrations and the risk of adverse effects associated with vadadustat. According to the manufacturer, coadministration with probenecid, a potent OAT1/OAT3 inhibitor, increased systemic exposure (AUC) of vadadustat by almost 2-fold. Increased systemic exposure to vadadustat may result in a rapid rise in hemoglobin and increase the risk of adverse reactions such as thromboembolic events, diarrhea, hypertension, liver injury, seizures, pneumonia, and increased cardiovascular and mortality risk.

MANAGEMENT: Close clinical and laboratory monitoring for adverse effects is advised if vadadustat is used concomitantly with moderate or potent OAT1 and/or OAT3 inhibitors. Additionally, close monitoring of hemoglobin levels is advised following initiation or discontinuation of treatment with moderate or potent OAT1/OAT3 inhibitors, and the vadadustat dosage adjusted as necessary in accordance with the prescribing information.

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.