Drug Interactions between astemizole and vadadustat

GENERALLY AVOID: Some beverages such as tonic water contain varying amounts of quinine. Coadministration of a single 430 mg dose of quinine has been shown to increase plasma concentrations of astemizole and its metabolite, desmethylastemizole. Elevated levels of these agents may cause a prolongation of the electrocardiographic QT interval and potentially fatal ventricular arrhythmias. Although pharmacokinetic data have indicated that the amounts of quinine in beverages (up to 80 mg quinine in 32 oz of tonic water) are not sufficient to produce a significant effect, the potential for an interaction exists if large amounts of tonic water are ingested. Also, grapefruit juice has been shown to inhibit CYP450 enzymes, which may lead to increased serum astemizole concentrations. The risk of life-threatening ventricular arrhythmias may be increased.

MANAGEMENT: Patients should be counseled to limit consumption of quinine-containing beverages and avoid grapefruit juice while they are taking astemizole.

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.