CYP3A4 and torsades de pointes: Its strong CYP3A4 induction may significantly reduce methadone concentrations and thereby decrease analgesia.21 As a dose-dependent inhibitor of CYP3A4, ribociclib may increase methadone concentrations and is also a QT prolonging agent (linked to the risk of potentially fatal torsades de pointes and arrhythmias21,45) which contraindicates coadministration at higher doses.21