Drug Interaction Report

GENERALLY AVOID: Theoretically, grapefruit and grapefruit juice may increase the plasma concentrations of hydroxychloroquine or chloroquine and the risk of toxicities such as QT interval prolongation and ventricular arrhythmias. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruit. Following coadministration with cimetidine, a weak to moderate CYP450 3A4 inhibitor, a 2-fold increase in chloroquine exposure occurred. Since chloroquine and hydroxychloroquine have similar structures and metabolic elimination pathways, a similar interaction may be observed with hydroxychloroquine. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

ADJUST DOSING INTERVAL: Administration with food or milk may reduce the incidence of hydroxychloroquine-related gastrointestinal adverse effects.

MANAGEMENT: Although clinical data are lacking, it may be advisable to avoid the consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract during hydroxychloroquine or chloroquine therapy. Hydroxychloroquine should be administered with food or milk to reduce the occurrence of gastrointestinal upset.

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.