Drug Interaction Report

MONITOR: Coadministration with vadadustat, an inhibitor of breast cancer resistance protein (BCRP), may increase the plasma concentrations and pharmacologic effects of BCRP substrates. The proposed mechanism involves decreased clearance due to inhibition of BCRP by vadadustat. According to product labeling, when vadadustat was coadministered with the BCRP substrates sulfasalazine, simvastatin and rosuvastatin, systemic exposure (AUC) of the substrates increased 4.5-fold, 2-fold, and 2 to 3-fold, respectively. However, no substantial change in exposure to sulfasalazine's active metabolite was observed.

MANAGEMENT: Caution is advised when vadadustat is used concomitantly with drugs that are substrates of the breast cancer resistance protein (BCRP) transporter. Monitoring for signs and symptoms of increased exposure to the BCRP substrate should be considered whenever vadadustat is added to or withdrawn from therapy. The prescribing information for concomitant medications may be consulted to assess the benefits versus risks of coadministration, as well as any dosage adjustments that may be required during coadministration and/or following the discontinuation of a BCRP inhibitor.

ADJUST DOSING INTERVAL: Oral cladribine may increase the bioavailability of other drugs, which may increase the risk or severity of adverse reactions. Cladribine tablets may contain hydroxypropyl betadex, which could form a complex with the active ingredients of other drugs, especially agents with low solubility. The clinical relevance of this interaction remains unknown.

MANAGEMENT: Administration of oral cladribine should be separated from any other oral drug by at least 3 hours.

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.