Methadone concentrations may also increase when coadministered with dasatinib, nilotinib, and imatinib, which are all weak/moderate CYP3A4 inhibitors.21 Methadone-related toxicity may cause sedation, respiratory depression, and QT prolongation associated with the risk of potentially fatal torsades de pointes and arrhythmias.46-49 Therefore, close monitoring including electrocardiogram (ECG) assessment is recommended,21 with dose adjustment where necessary. This evidence concerns the gene CYP3A4 and respiratory depression.