Methadone as the initial long-acting opioid in children with advanced cancer.

Abstract

224 Background: Methadone is an attractive medication for treating children with advanced cancer who have chronic pain, as it is the only long-acting opioid available as a liquid. This formulation allows for precise dosing that is not possible with the fixed dose of extended release tablets or transdermal patches. Additionally, it can be used in children unable to reliably swallow tablets. Many pediatric oncologists are concerned with methadone’s complex pharmacodynamics and pharmacokinetics, and so it is often relegated to being the long-acting opioid to use only after long-acting morphine, long-acting oxycodone, and fentanyl transdermal patches have proven to be ineffective in controlling pain. We believe that methadone has a role as the first long-acting opioid in children who have uncontrolled pain while only on immediate-release mu opioid agonists. Methods: Retrospective chart review of 52 consecutive patients referred to Pediatric Supportive Care for pain management started on methadone as their first long-acting opioid. Data collected at baseline and first follow up visit (F1) included child- and parent-reported outcomes for various physical and psychological symptoms, opioid side effects and other clinical data. All symptoms were rated on a 5 point scale: 0 (not at all), 1 (a little bit), 2 (kind of), 3 (quite a bit) and 4 (a lot). Results: Of 52 eligible patients, a majority (47, 90.3%) were assessed at F1. Reasons for not evaluating patients at F1 included death (3) (none died of cardiac arrhythmia or opioid related toxicity) and transfer of care to another facility (2). Pain as scored by the child was 3.6/4 at baseline and 1.8/4 at F1 (P < 0.0001). Pain as scored by the parent was 3.5/4 at baseline and 1.4 at F1 (P < 0.0001). A majority of patients (33, 70.2%) at F1 did not need a change in their methadone dose. A small number (10, 21.3%) needed an increase in their methadone dose due to inadequate pain control; a few (4, 8.5%) had a lower methadone dose but all were part of tapering methadone due to resolution of the original pain syndrome, not due to opioid toxicity. Conclusions: Initiation of methadone was effective and safe as the first long-acting opioid in children with pain due to advanced cancer.

Methadone for Cancer Pain in Pediatric End-of-Life Care

“…13 A dose of 0.2 mg/kg per day was used for methadone as an initial long-acting opioid with reported success in a cohort of 52 pediatric oncology patients. 12 Anghelescu et al reported individualized starting doses ranging from 0.06 to 3.8 mg/kg per day for the treatment of pediatric cancer pain. 15 This range partially reflects high variability in morphine to methadone conversion ratios.…”

“…Despite an increased interest in the use of methadone and its potential advantages over other opioids, evidence in pediatric oncology remains sparse, to date consisting only of case reports and case series. 2,11 -16 Both pediatric oncologists 17 and pediatric palliative care physicians 18 have reported a lack of experience with and education in the use of methadone, further justifying the need for additional data regarding the use of methadone in the pediatric oncology setting. Herein, we describe a single institution’s experience with dosing, duration, monitoring, and other clinical considerations for using methadone to treat cancer pain in pediatric EOL care.…”

First-line methadone for cancer pain: titration time analysis

“…Initial median (range) pain intensity was 8 (4-10) and the PPG was 2 (0-4). Irruptive pain was present in 11/62 patients (18%) with a median intensity of 7 (6)(7)(8)(9). Fifty-ve out of 62 patients who initiated methadone (89%) completed the 7-day observation period.…”

“…A main concern relates to its variable and erratic half-life and slow elimination phase with the risk of accumulation and delayed toxicity [5,7], requiring cautious initiation and titration. In recent years, some studies began to document methadone´s safety and e cacy as a rst line of treatment for cancer pain in palliative care (PC) patients [8,9]. Still there is limited evidence in relation to the modality of titration and the timing for pain control and dose stabilization [8].…”

Attitudes, Beliefs, and Practices of Pediatric Palliative Care Physicians Regarding the Use of Methadone in Children With Advanced Cancer

“…This might allow them to safely administer it to even the very youngest children. 3 Most research on methadone in children for pain is limited to reports on the prolongation of the corrected QT (QTc) interval. 4e6 The use of methadone for pain in children with cancer is limited to a few case series.…”