Drug Interactions between adagrasib and erythromycin / sulfisoxazole

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Adagrasib can cause concentration-dependent, prolongation of the QT interval. Coadministration with other agents that can prolong the QT interval may increase the risk of ventricular arrhythmias including torsade de pointes and sudden death. According to cardiac electrophysiology data provided by the manufacturer, the mean (90% CI) QTcF change from baseline was 18 ms at the mean steady-state maximum concentration (Cmax,ss) after administration of adagrasib 600 mg twice daily. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

GENERALLY AVOID: Adagrasib may increase the plasma concentrations and adverse effects of CYP450 3A4 substrates. Adagrasib is a potent inhibitor as well as a substrate of CYP450 3A4. In pharmacokinetic studies, adagrasib 400 mg twice daily increased midazolam (a sensitive CYP450 3A4 substrate) peak plasma concentration (Cmax) and systemic exposure (AUC) by 4.8-fold and 21-fold, respectively. Adagrasib 600 mg twice daily is predicted to increase midazolam Cmax and AUC by 3.1-fold and 31-fold, respectively.

MANAGEMENT: Coadministration of adagrasib with other drugs that can prolong the QT interval and/or are sensitive substrates of CYP450 3A4 should generally be avoided.