Drug Interaction Report

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.

MONITOR: Smoking and alcohol consumption during therapy with vadadustat may increase the risk of gastrointestinal erosions. Serious erosions, including gastrointestinal bleeding and the need for red blood cell transfusions, have been reported during vadadustat clinical trials. Patients with a history of gastrointestinal erosion, peptic ulcer disease, and current tobacco smokers and alcohol drinkers may be at higher risk of gastrointestinal injury.

MANAGEMENT: Caution is advised if vadadustat is prescribed to current tobacco smokers or alcohol drinkers. Patients should be advised to contact their physician if they develop potential signs and symptoms of gastrointestinal injury such as abdominal pain, hematemesis, trouble swallowing, chest or throat pain, and/or black, tarry stools.