Evaluation of QTc Interval Prolongation Among Patients With Cancer Using Enteral Methadone

Abstract

The effect of methadone on corrected QT interval (QTc) in patients with cancer pain is not well-known. Objectives: To describe and characterize the effect of low-, moderate-, and high-dose enteral methadone on QTc interval in patients with cancer. Methods: Retrospective cohort study including patients prescribed enteral methadone during the 27-month study period. Participants were divided into 3 methadone daily dose groups: <30 (low dose), 30 to 59 (moderate dose), !60 (high dose) mg. The primary outcome was the incidence of QTc prolongation (>450 ms for females and >430 ms for males). Secondary outcomes included the magnitude of change in QTc after starting methadone, the incidence of clinically significant QTc prolongation (>500 ms) and the prevalence of torsades de pointes and syncope. Results: Two hundred three patients met study inclusion criteria: 91 (45%) low dose, 52 (26%) moderate dose, and 60 (29%) high dose. Incidence of QTc prolongation for low-, moderate-, and high-dose groups was 50 (55%), 37 (71%), and 43 (72%), respectively (P ¼ .039, low vs high dose). Incidence of clinically significant QTc prolongation was 10 (11%), 4 (8%), and 7 (12%) for low-, moderate-, and high-dose groups. For patients without QTc prolongation prior to initiating methadone, 62% of moderate-dose patients and 67% of high-dose patients had QTc prolongation, while taking methadone. Conclusion: This study found a notably high incidence of QTc prolongation in patients with cancer using enteral methadone. Future studies should aim to determine the risk of adverse cardiac effects in the cancer population and determine appropriate monitoring of methadone for pain management.

The Use of Low-Dose Methadone as Add-On to Regular Opioid Therapy in Cancer-Related Pain at End of Life: A National Swedish Survey in Specialized Palliative Care

“…This is of importance since there are concerns about safety in ambulatory settings due to the inherent risk of respiratory depression and QTc prolongation associated with methadone use. 28 In our material, patients in home care settings were safely initiated on methadone. Our findings are corroborated by two other studies.…”

Methadone in Cancer Pain

“…[ 26 ] Methadone has been established to be safe beyond the hospital setting and has been corroborated by various studies to be safe despite the inherent risk of respiratory depression and the risk of arrhythmia due to QTc prolongation. [ 14 59 60 61 62 ]…”

How to Prescribe Drugs With an Identified Proarrhythmic Liability

“…In contrast to the medical specialties focusing on LQTS, drug‐induced QT prolongation is relevant to a much wider group of health care professionals involved in therapeutic decisions, for example, physicians in family practice and a wide variety of medical specialties, physician assistants, nurses, and pharmacists and hence this article's focus on this topic. A wide range of drugs and drug classes for many conditions as diverse as liver and kidney disease, chronic obstructive pulmonary disease, psychiatric conditions, and posttraumatic stress disorder have an identified proarrhythmic liability. If prescribed to patients with certain risk factors, they can occasionally precipitate bradyarrhythmias and tachyarrhythmias, including TdP.…”