Drug Interactions between Ozempic and rimegepant

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.

ADJUST DOSING INTERVAL: Coadministration with grapefruit or grapefruit juice may increase the plasma concentrations of rimegepant. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruit. Concomitant administration of a single dose of rimegepant (75 mg) with itraconazole, a strong CYP450 3A4 inhibitor, at steady state increased the systemic exposure (AUC) and peak plasma concentration (Cmax) of rimegepant by 4-fold and approximately 1.5-fold, respectively. The manufacturer also states that concomitant administration of rimegepant with a moderate CYP450 3A4 inhibitor may increase rimegepant AUC by less than 2-fold. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). 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.

MONITOR: When administered with a high-fat meal under fed condition, Tmax was delayed by 1 hour, which resulted in a 42% to 53% reduction in Cmax and a 32% to 38% reduction in AUC. However, the impact of this reduction on rimegepant efficacy remains unknown.

MANAGEMENT: Rimegepant may be administered with or without food. Until more information is available, patients receiving rimegepant may want to avoid the regular consumption of grapefruits and grapefruit juice to prevent undue increases in plasma levels and systemic effects of rimegepant. If grapefruit or grapefruit juice is consumed concomitantly with rimegepant, the manufacturer recommends avoiding another dose of rimegepant within 48 hours.