Drug Interaction Report

MONITOR: Coadministration with vadadustat may decrease the plasma concentrations and therapeutic efficacy of drugs that are substrates of the CYP450 2B6 isoenzyme. Vadadustat is an inducer CYP450 2B6 in vitro. However, clinical data are not available.

MANAGEMENT: Some authorities recommend using caution when vadadustat is used concomitantly with drugs that are substrates of CYP450 2B6, particularly sensitive substrates or those with a narrow therapeutic range. Monitoring for potential loss of therapeutic efficacy is recommended. 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 CYP450 2B6 inducer.

CONTRAINDICATED: Consumption of ethanol during treatment with disulfiram may cause flushing, nausea, blurred vision, dyspnea, tachypnea, tachycardia, and hypotension. Death has been reported. The mechanism is probably related to inhibition of aldehyde dehydrogenase, the enzyme responsible for the oxidation of acetaldehyde to acetyl CoA. Accumulation of acetaldehyde probably results.

MANAGEMENT: Ethanol should be avoided in patients receiving disulfiram.

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.