Drug Interaction Report

ADJUST DOSING INTERVAL: Taking oral semaglutide with food, beverage, or other oral medications may alter semaglutide absorption and exposure. In a controlled study with healthy volunteers, limited or no measurable semaglutide exposure was observed in subjects that were fed 30 minutes prior to taking oral semaglutide, while all subjects that fasted overnight and 30 minutes after the oral semaglutide dose had measurable semaglutide exposure. Area under the curve (AUC) and semaglutide peak plasma concentration (Cmax) were approximately 40% greater in subjects that fasted compared to those who did not. AUC and Cmax were also increased with a post-dose fasting period greater than 30 minutes.

MANAGEMENT: It is recommended that oral semaglutide be taken 30 minutes before the first food, beverage, or other oral medications of the day with no more than 4 ounces of plain water to ensure its efficacy. Fasting longer than 30 minutes after the oral semaglutide dose may lead to increased gastrointestinal side effects including nausea, vomiting, or diarrhea.

In vitro data suggest that grapefruit juice may inhibit the CYP450 3A4 first-pass metabolism of dofetilide. Decreased first-pass metabolism may increase dofetilide concentrations and increase the risk of QT interval prolongation and arrhythmias. The clinical significance is unknown, since dofetilide has a high oral bioavailability and a low affinity for CYP450 3A4. The manufacturer recommends caution.