{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:37:36Z","timestamp":1787017056884,"version":"build-2736575974"},"reference-count":24,"publisher":"BMJ","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Reg Anesth Pain Med"],"accepted":{"date-parts":[[2026,2,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Methadone is commonly used as an alternative to other opioids for managing cancer-related pain. High-dose methadone, primarily in opioid dependence treatment, has been associated with QTc prolongation and dangerous arrhythmias. The cardiovascular effects of methadone at lower doses, as used in cancer pain management, remain less well characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective chart review of 492 adult patients who received methadone for cancer-related pain management. For each patient, we collected demographic and clinical data, including age, sex, cancer diagnosis, initial methadone dosage, adjuvant medications, and comorbidities. QTc interval measurements were extracted from ECGs performed at baseline (within 12 months prior to methadone initiation) and at follow-up intervals of 0\u20136 months, 6\u201312 months, and \u226512 months after initiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The linear mixed-effects model shows a statistically significant increase in QTc interval by 4.36 ms at \u226512 months after methadone initiation. The prevalence of cardiac comorbidities was associated with a statistically significant increase in QTc by 9.40 ms. No other timeframe, demographic characteristic, or clinical characteristic that we investigated was associated with a statistically significant change in QTc. The overall proportion of patients with QTc prolongation increased modestly from 3% at baseline to 6.8% after 12 months following the initiation of methadone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this large retrospective cohort of oncology patients receiving methadone for pain management, methadone was associated with a small but statistically significant increase in QTc interval \u226512 months after starting therapy, with a mean increase of approximately 4 ms. This magnitude of QTc change is unlikely to produce meaningful clinical manifestations for most patients. These findings support the low risk of QTc prolongation for most patients with cancer taking methadone and encourage a risk-stratified approach to methadone use in cancer pain with targeted ECG monitoring regimens for patients with elevated baseline QTc or underlying cardiac disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rapm-2025-107328","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T13:55:14Z","timestamp":1771336514000},"page":"rapm-2025-107328","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluating the risk of methadone and QTc interval prolongation in an oncologic population"],"prefix":"10.1136","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6675-8529","authenticated-orcid":false,"given":"Daniel Yuwen","family":"Li","sequence":"first","affiliation":[{"name":"University of Texas McGovern Medical School, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Kim","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1028-8904","authenticated-orcid":false,"given":"Saba","family":"Javed","sequence":"additional","affiliation":[{"name":"Department of Pain Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Billy","family":"Huh","sequence":"additional","affiliation":[{"name":"Department of Pain Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,2,17]]},"reference":[{"key":"2026021705550706000_rapm-2025-107328v1.1","doi-asserted-by":"crossref","first-page":"2755","DOI":"10.1007\/s11136-024-03725-w","article-title":"Comprehensive assessment of pain characteristics, quality of life, and pain management in cancer patients: a multi-center cross-sectional study","volume":"33","author":"Shrestha","year":"2024","journal-title":"Qual Life Res"},{"key":"2026021705550706000_rapm-2025-107328v1.2","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1097\/NJH.0000000000000507","article-title":"Cancer Pain and Quality of Life","volume":"21","author":"Rodriguez","year":"2019","journal-title":"J Hosp Palliat Nurs"},{"key":"2026021705550706000_rapm-2025-107328v1.3","doi-asserted-by":"crossref","DOI":"10.1097\/PR9.0000000000000979","article-title":"Use of methadone as an alternative to morphine for chronic pain management: a noninferiority retrospective observational study","volume":"6","author":"Moreira de Barros","year":"2021","journal-title":"Pain Rep"},{"key":"2026021705550706000_rapm-2025-107328v1.4","doi-asserted-by":"crossref","first-page":"7613","DOI":"10.3390\/curroncol31120561","article-title":"Methadone in Cancer-Related Neuropathic Pain: A Narrative Review","volume":"31","author":"Ragaban","year":"2024","journal-title":"Curr Oncol"},{"key":"2026021705550706000_rapm-2025-107328v1.5","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1111\/bcpt.13975","article-title":"Methadone pharmacokinetics in opioid agonist treatment: Influencing factors and clinical implications","volume":"134","author":"Chalabianloo","year":"2024","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"2026021705550706000_rapm-2025-107328v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100120"},{"key":"2026021705550706000_rapm-2025-107328v1.7","doi-asserted-by":"publisher","DOI":"10.1080\/10550880903436010"},{"key":"2026021705550706000_rapm-2025-107328v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2008.06.018"},{"key":"2026021705550706000_rapm-2025-107328v1.9","doi-asserted-by":"publisher","DOI":"10.1592\/phco.23.6.802.32186"},{"key":"2026021705550706000_rapm-2025-107328v1.10","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.jpain.2020.04.004","article-title":"Methadone in Pain Management: A Systematic Review","volume":"22","author":"Hanna","year":"2021","journal-title":"J Pain"},{"key":"2026021705550706000_rapm-2025-107328v1.11","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1007\/s40263-020-00743-3","article-title":"Methadone for Pain Management: A Pharmacotherapeutic Review","volume":"34","author":"Kreutzwiser","year":"2020","journal-title":"CNS Drugs"},{"key":"2026021705550706000_rapm-2025-107328v1.12","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1111\/pme.12658","article-title":"The QTc effect of low-dose methadone for chronic pain: a prospective pilot study","volume":"16","author":"Grodofsky","year":"2015","journal-title":"Pain Med"},{"key":"2026021705550706000_rapm-2025-107328v1.13","unstructured":"Woosley RL , Heise CW , Gallo T , et al . QTdrugs list [CredibleMeds (AZCERT, Inc]. n.d. Available: https:\/\/www.crediblemeds.org"},{"key":"2026021705550706000_rapm-2025-107328v1.14","doi-asserted-by":"publisher","DOI":"10.1002\/sim.3697"},{"key":"2026021705550706000_rapm-2025-107328v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2013.01.013"},{"key":"2026021705550706000_rapm-2025-107328v1.16","doi-asserted-by":"crossref","first-page":"579","DOI":"10.21037\/apm.2020.02.01","article-title":"Levorphanol versus methadone use: safety considerations","volume":"9","author":"Haider","year":"2020","journal-title":"Ann Palliat Med"},{"key":"2026021705550706000_rapm-2025-107328v1.17","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.121.023482","article-title":"Methadone Blockade of Cardiac Inward Rectifier K+ Current Augments Membrane Instability and Amplifies U Waves on Surface ECGs: A Translational Study","volume":"11","author":"Klein","year":"2022","journal-title":"J Am Heart Assoc"},{"key":"2026021705550706000_rapm-2025-107328v1.18","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.194670"},{"key":"2026021705550706000_rapm-2025-107328v1.19","doi-asserted-by":"crossref","first-page":"2850","DOI":"10.1002\/cncr.31389","article-title":"Polypharmacy and patterns of prescription medication use among cancer survivors","volume":"124","author":"Murphy","year":"2018","journal-title":"Cancer"},{"key":"2026021705550706000_rapm-2025-107328v1.20","doi-asserted-by":"crossref","DOI":"10.1186\/s40360-017-0181-2","article-title":"Frequency, characteristics and risk factors of QT interval prolonging drugs and drug-drug interactions in cancer patients: a multicenter study","volume":"18","author":"Khan","year":"2017","journal-title":"BMC Pharmacol Toxicol"},{"key":"2026021705550706000_rapm-2025-107328v1.21","unstructured":"International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) . E14: the clinical evaluation of QT\/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs. Geneva, 2005."},{"key":"2026021705550706000_rapm-2025-107328v1.22","doi-asserted-by":"publisher","DOI":"10.1113\/JP270526"},{"key":"2026021705550706000_rapm-2025-107328v1.23","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1080\/17581869.2025.2457316","article-title":"The effect of oral methadone on the QTc interval in cancer pain patients","volume":"15","author":"Sheen","year":"2025","journal-title":"Pain Manag"},{"key":"2026021705550706000_rapm-2025-107328v1.24","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.jpainsymman.2019.05.021","article-title":"Corrected QT Interval Prolongation in Pediatric and Young Adult Patients on Methadone for Cancer-Related Pain","volume":"58","author":"Madden","year":"2019","journal-title":"J Pain Symptom Manage"}],"container-title":["Regional Anesthesia &amp; Pain Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/rapm-2025-107328","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T13:55:17Z","timestamp":1771336517000},"score":1,"resource":{"primary":{"URL":"https:\/\/rapm.bmj.com\/lookup\/doi\/10.1136\/rapm-2025-107328"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,17]]},"references-count":24,"alternative-id":["10.1136\/rapm-2025-107328"],"URL":"https:\/\/doi.org\/10.1136\/rapm-2025-107328","relation":{},"ISSN":["1098-7339","1532-8651"],"issn-type":[{"value":"1098-7339","type":"print"},{"value":"1532-8651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,17]]}}}