Drug Interaction Report

ADJUST DOSING INTERVAL: Coadministration of vadadustat with oral products containing multivalent cations such as calcium, magnesium, or aluminum may significantly decrease the bioavailability of vadadustat. The mechanism of this interaction has not been fully described but may involve the formation of an insoluble complex or chelate with multivalent cations that is poorly absorbed from the gastrointestinal tract. According to product labeling, when non-iron-containing phosphate binders were coadministered-administered with vadadustat, the systemic exposure (AUC) and peak plasma concentration (Cmax) decreased by 55% and 52%, respectively.

MANAGEMENT: Vadadustat should be administered at least one hour before, or two hours after the administration of oral non-iron-containing phosphate binders or other medicinal products whose primary component consists of multivalent cations such as calcium, magnesium, or aluminum.

ADJUST DOSING INTERVAL: Sevelamer may decrease the oral bioavailability of concomitantly administered drugs. While clinical data are lacking for most drugs, the intestinal absorption of some may be impaired due to sevelamer's binding capabilities.

MANAGEMENT: As a precaution, drugs that can be adversely affected by alterations in blood levels should be administered 1 hour before or 3 hours after sevelamer.

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.