Extreme doses of intravenous methadone for severe pain in two children with cancer

Abstract

We describe the effect and side effects in two children with cancer treated with intravenous methadone in extreme doses (>10 mg/kg/day) due to vincristine-induced neuropathy where surgical procedures provoked severe neuropathic pain. The maximum daily dose was 33 and 25 mg/kg/day. Methadone remained effective at adjusted doses. Few side effects were reported. No significant changes in paraclinical data were observed. Prolonged QTc-interval occurred only during concomitant treatment with fluconazole. In conclusion, methadone should be seen as a part of the armamentarium against cancer-related pain. Methadone can be used in extreme doses with appropriate monitoring by clinicians experienced in its use.

The frequency of QTc prolongation among pediatric and young adult patients receiving methadone for cancer pain

“…Little is known, however, about the effects of methadone on the QTc in children except its potential to increase the QTc interval . There is a case report of methadone‐induced prolongation of the QTc in a child, yet this child received extremely high intravenous (IV) doses, which both are known risk factors in adults for prolongation of the QTc interval …”

“…9 Little is known, however, about the effects of methadone on the QTc in children except its potential to increase the QTc interval. 10,11 There is a case report of methadone-induced prolongation of the QTc in a child, 12 yet this child received extremely high intravenous (IV) doses, which both are known risk factors in adults for prolongation of the QTc interval. 13,14 The purpose of this study was to determine the frequency of QTc prolongation in a series of children and young adults treated with methadone for cancer-related pain by a Pediatric Supportive Care Service.…”

The effect of thioctic acid on allodynia in a rat vincristine-induced neuropathy model

“…1,2 Since the pathogenesis of vincristine induced neuropathy is not clearly understood, various treatments are prescribed empirically, including tricyclic antidepressants, anticonvulsants, opioids, nonsteroidal anti-inflammatory agents and a-adrenergic agonists. [3][4][5] The efficacy of these drugs in the treatment of neuropathy is limited, however, and some have poor safety profiles.…”

Effects of Methadone on Corrected Q-T Interval Prolongation in Critically Ill Children

“…12 In 2 pediatric patients (ages 11 and 17 years) receiving methadone for chronic pain, 1 had no change in QTc interval and the other had QTc prolongation in the setting of concomitant QTc-prolonging drugs. 7 In a recent retrospective review of 37 children with cancer-related pain, the mean QTc during methadone treatment was longer than at baseline (447 vs. 437 msec, respectively). 8 Our findings are inconsistent with data in adults, in whom methadone has been associated with varying degrees of QTc prolongation (16%-23% change in QTc interval), and with torsades de pointes in up to 4% of patients.…”

“…3 Existing evaluations of the QTc-prolonging effects of methadone in children are limited to very small studies and case reports (73 total children) that reach varying conclusions regarding the degree of QTc prolongation induced by methadone. [4][5][6][7][8] Notably, existing studies have largely excluded critically ill children, including those with underlying cardiac disease. Critically ill children are among the most frequent recipients of methadone therapy.…”