Evaluation of QTc Interval Prolongation Among Cancer Patients Using Oral Methadone (FR420D)

Abstract

•Describe the incidence of QTc prolongation in cancer patients taking oral methadone.•Discuss the effect of increasing methadone doses on QTc prolongation in cancer patients. Methadone’s effect on QTc in cancer pain patients is not well known. The lone published study may not represent all palliative prescribing patterns. The objective of this study is to describe and characterize the effect of low-, moderate-, and high-dose methadone on QTc in cancer patients. This retrospective cohort study was exempt from IRB. Cancer patients with an order for enteral methadone over a 27-month period were included. Participants were divided into three methadone daily dose groups: <30mg (low-dose), 30 to 59mg (moderate-dose), >60mg (high-dose). Primary outcome was the incidence of QTc prolongation in each group. Secondary outcomes included change in QTc from baseline to study electrocardiogram (ECG), incidence of clinically significant QTc prolongation (> 500ms), and prevalence of adverse cardiac outcomes including Torsades de Pointes. A total of 203 of 430 met the inclusion criteria for the study; low-dose: 91 patients (45%), moderate-dose: 52 (26%), and high-dose: 60 (29%). Incidence of QTc prolongation for low-, moderate-, and high-dose groups was 50 (55%), 37 (71%), and 43 (72%), respectively (p=0.039). Incidence of clinically significant QTc prolongation was 10 (11%), 4 (8%), and 7 (12%) for low-, moderate-, and high-dose groups. Median change in QTc interval from baseline to study ECG for low-, moderate-, and high-dose groups was 6ms, 18ms, 14.5ms, respectively (p=0.068). Sixty-two percent of patients in the moderate-dose group and 67% of patients in the high-dose group without QTc prolongation at baseline had QTc prolongation at study ECG. Our data suggest there may be a higher incidence of QTc prolongation in patients using oral methadone in the cancer population than previously defined in the literature.