Abemaciclib (Verzenio™)

Drug-drug interactions in breast cancer patients treated with CDK4/6 inhibitors

“…The AUC values of abemaciclib and its active metabolites increase by 9% when administered with a high-fat meal in healthy subjects. Abemaciclib is extensively metabolized by CYP3A4 with formation of equipotent active metabolites [17]. The V d is approximately 690 L. Improved central nervous system penetration has been demonstrated for abemaciclib with concentrations of parent drug and active metabolites in cerebrospinal fluid comparable to unbound plasma concentrations [12,18].…”

“…For example, co-administration of clarithromycin has been reported to increase abemaciclib AUC by 237% and C max by 30%, respectively, and those of the total active metabolites by 119% and 7%, respectively [33]. As a consequence, clarithromycin and abemaciclib combination should be avoided or, alternatively, abemaciclib dose should be reduced from 200 or 150 mg to 100 mg twice daily [17]. Accordingly, daily dose of palbociclib needs to be reduced from 125 to 75 mg and that of ribociclib from 600 to 400 mg, in the presence of strong CYP3A4 inhibitors [21].…”

“…However, selection of a specific antifungal agent needs to be carefully evaluated by taking into account that DDIs involving antifungals are common during multiple treatments [32,35]. For example, ketoconazole is predicted to increase the AUC of abemaciclib by up to 16-fold with potential toxicity; this combination should be therefore avoided and non-interacting alternatives considered in patients receiving CDK4/6 inhibitors [17]. A possible alternative is represented by echinocandins, which display a lower potential for DDIs [35].…”