Drug Interactions between Kimyrsa and repaglinide

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of repaglinide, which is metabolized by the isoenzyme in the intestine and liver. In nine healthy volunteers, pretreatment with the CYP450 3A4 inducer rifampin (600 mg orally once a day for 5 days) decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of repaglinide (0.5 mg single oral dose) by 41% and 57%, respectively, compared to placebo. The mean half-life was decreased by 27%, from 1.5 to 1.1 hours, by rifampin. Decreases in repaglinide Cmax (range 15% to 73%), AUC (range 30% to 78%), and half-life (range 1% to 37%) values were observed in every subject. There was also a significant difference in the glucose response to repaglinide between the rifampin and placebo phases. Specifically, rifampin reduced the mean decremental AUC from 0 to 3 hours of blood glucose by 76% and the maximum decrease in blood glucose concentration by 35% compared to placebo.

MANAGEMENT: Because the antidiabetic effect of repaglinide is dose- and concentration-dependent, patients treated concomitantly with rifampin may require a higher dosage of repaglinide. Blood glucose should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy in patients stabilized on their existing antidiabetic regimen, and the repaglinide dosage adjusted as necessary. Patients should be advised to contact their physician if they experience loss of glycemic control.