Drug Interaction Report

MONITOR: Coadministration with vadadustat, a weak CYP450 2C9 inhibitor, may increase the plasma concentrations and the risk of adverse effects of drugs that are substrates of CYP450 2C9. A drug interaction study evaluating the effect of vadadustat (600 mg) on the pharmacokinetics of celecoxib, a CYP450 2C9 substrate, showed an increase in peak plasma concentration (Cmax) and systemic exposure (AUC) by 60% and 11%, respectively.

MANAGEMENT: Some authorities recommend using caution when vadadustat is used in combination with CYP450 2C9 substrates. Monitoring for signs and symptoms of increased exposure to the CYP450 2C9 substrate should be considered whenever vadadustat is added to or withdrawn from therapy.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 an CYP450 2C9 inhibitor.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of ramelteon. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

ADJUST DOSING INTERVAL: Administration of ramelteon with or immediately after a high-fat/heavy meal may delay the onset of hypnotic effects. In study subjects, administration of a 16 mg dose of ramelteon with a high-fat meal decreased the peak plasma drug concentration (Cmax) by 22% and delayed the median time to reach peak plasma drug concentration (Tmax) by approximately 45 minutes compared to administration in a fasted state.

MANAGEMENT: Patients receiving ramelteon should be advised to avoid the consumption of alcohol. For faster sleep onset, ramelteon should not be administered with or immediately after a high-fat/heavy meal.

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.