Methadone Switching for Cancer Pain: A New Classification of Initiation Protocols, Based on a Critical Literature Review

Treillet, Erwan; Giet, Olivier; Picard, Stéphane; Laurent, Sophie; Seresse, Laure

doi:10.1089/jpm.2021.0309

Cited by 6 publications

(3 citation statements)

References 46 publications

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“…2,3 However, the use of methadone for cancer pain is challenging because it has a complicated and inconsistent conversion ratio from converting the pre-switching opioid dose to methadone. [4][5][6] Indeed, methadone accumulates in the adipose tissue because of its lipophilicity; binds strongly to plasma proteins, causing methadone levels to vary; and gets influenced by individual body compositions. 3 Moreover, the bioavailability of methadone ranges widely from 70% to 90%.…”

Section: Introductionmentioning

confidence: 99%

A Survey of the Status of Methadone Switching in Japan Using a Hospital‐Based Administrative Claims Database

Imai,

Aoki,

Ikegami

et al. 2023

The Journal of Clinical Pharma

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Methadone is generally used for the management of cancer pain in patients who cannot obtain adequate analgesia from other strong opioids; however, it has a complicated and inconsistent conversion ratio from pre‐switching opioid dosage to methadone. This issue may be pronounced in Japan because only oral tablets are commercially available. We aimed to elucidate the status of methadone switching in Japan, focusing on its dosage. Using a Japanese hospital‐based administrative claims database, we included patients who switched to methadone between April 2008 and January 2021. The proportion of methadone switching completion that required more than the defined conversion ratio in the Japanese package insert (called “high‐dose methadone switching”) was evaluated as a primary endpoint. Other endpoints included “the duration from initiation to completion of methadone switching” and “factors affecting high‐dose methadone switching by using multivariate logistic regression analysis.” Of 1,585 patients who received methadone, 370 were enrolled. Among those, 130 (35.1%) received high‐dose methadone switching. The median duration of methadone switching completion (12 days) was longer in the high‐dose methadone switching group than in other patients. Four variables were identified as factors affecting high‐dose methadone switching. Younger age and outpatient status increased the risk of requiring high‐dose methadone switching, whereas the concomitant use of nonsteroidal anti‐inflammatory drugs and fentanyl as a pre‐switching opioid decreased the risk. In conclusion, more than 30% of the patients underwent high‐dose methadone switching and required long completion periods, suggesting that methadone switching remains challenging in Japan.This article is protected by copyright. All rights reserved

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Section: Introductionmentioning

confidence: 99%

A Survey of the Status of Methadone Switching in Japan Using a Hospital‐Based Administrative Claims Database

Imai,

Aoki,

Ikegami

et al. 2023

The Journal of Clinical Pharma

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“…Methadone (MTD) is the most commonly used drug in the world for treating heroin and prescription-opioid addiction due to its safety, efficacy, and low cost [ 1 ]. Furthermore, due to its distinctive pharmacokinetic and pharmacodynamic properties—such as its high oral bioavailability, its longer half-life when compared to other opioids, its non-competitive antagonist action on NMDA receptors, and its inhibitory action on serotonin and noradrenaline reuptake—MTD is a drug that can be used to treat both chronic and acute pain [ 2 ]; MTD is now used to treat both acute post-operatory pain and chronic pain, both cancer and non-cancer related [ 3 , 4 , 5 ]. It is estimated that over 300,000 patients in Europe are receiving MTD maintenance therapy for opioid addiction (750,000 patients worldwide); MTD was added to the WHO’s list of essential drugs in 2005 due to the reduction in mortality, relapses, and illicit activities it ensures [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Methadone Maintenance and QT-Interval: Prevalence and Risk Factors—Is It Effective to Switch Therapy to Levomethadone?

Santin,

Verlato,

Tfaily

et al. 2023

Biomedicines

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Methadone is a chiral synthetic opioid primarily used to treat heroin and prescription-opioid addiction: the (R)-enantiomer (Levomethadone) activates the µ-opioid receptor more potently than the (S)-enantiomer, which is a more potent blocker of the hERG potassium channels, resulting in QTc prolongation. The purpose of this retrospective study was to assess the effect of methadone on the QTc interval and to investigate the benefits of Levomethadone. The electrocardiograms of 165 patients taking methadone at various dosages and for different periods of time were examined: the QTc value was manually measured and then adjusted using Bazett’s formula. Data analysis revealed a linear association between the dosage of methadone and QTc length; no correlation was found between the QTc value and gender, age, or duration of therapy. In total, 14% of the sample (23 patients) showed a prolongation of the QTc interval (>470 ms in males and >480 ms in females); 10 of the 23 patients with QTc elongation underwent a change of therapy from Methadone to Levomethadone—in 90% of these patients, a normalization in the QTc length was established. This study confirmed the role of methadone, specifically its dosage, in QTc prolongation and the efficiency of Levomethadone as an adequate therapeutic substitute in these circumstances. This study validates the importance of careful electrocardiographic monitoring in methadone-treated patients.

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“…Methadone (MTD) is the most commonly used drug in the world for treating heroin and prescription-opioid addiction due to its safety, efficacy, and low cost [1]. Furthermore, due to its distinctive pharmacokinetic and pharmacodynamic properties-such as its high oral bioavailability, its longer half-life when compared to other opioids, its noncompetitive antagonist action on NMDA receptors, and its inhibitory action on serotonin and noradrenaline reuptake-MTD is a drug that can be used to treat both chronic and acute pain [2]; MTD is now used to treat both acute post-operatory pain and chronic pain, both cancer and non-cancer related [3][4][5]. It is estimated that over 300,000 patients in Europe are receiving MTD maintenance therapy for opioid addiction (750,000 patients worldwide); MTD was added to the WHO's list of essential drugs in 2005 due to the reduction in mortality, relapses, and illicit activities it ensures [6].…”

Section: Introductionmentioning

confidence: 99%

Methadone Maintenance and QT-interval: Prevalence and Risk Factors. Is it Effective to Switch Therapy to Levomethadone?

Santin,

Verlato,

Tfaily

et al. 2023

Preprint

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(1) Methadone is a chiral synthetic opioid primarily used to treat heroin and prescription-opioid addiction: the (R)-enantiomer (Levomethadone) activates the µ-opioid receptor more potently than the (S)-enantiomer, which is a more potent blocker of the hERG potassium channels, resulting in QTc prolongation. The purpose of this study is to assess the effect of methadone on the QTc interval and to investigate the benefits of Levomethadone. (2) The electrocardiograms of 165 patients taking methadone at various dosages and for different periods of time were examined: the QTc value was manually measured and then adjusted using Bazett's formula. (3) Data analysis revealed a linear association between the dosage of methadone and QTc length; no correlation was found between the QTc value and gender, age, or duration of therapy. 14% of the sample (23 patients) showed a prolongation of the QTc interval. 10 of the 23 patients with QTc elongation underwent a change of therapy from Methadone to Levomethadone: in 90% of these patients, a normalization in the QTc length was established. (4) This study confirmed the role of methadone, specifically its dosage, in QTc prolongation and the efficiency of Levomethadone as an adequate therapeutic substitute in these circumstances. This study validates the importance of a careful electrocardiographic monitoring in methadone-treated patients.

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Methadone Switching for Cancer Pain: A New Classification of Initiation Protocols, Based on a Critical Literature Review

Cited by 6 publications

References 46 publications

A Survey of the Status of Methadone Switching in Japan Using a Hospital‐Based Administrative Claims Database

A Survey of the Status of Methadone Switching in Japan Using a Hospital‐Based Administrative Claims Database

Methadone Maintenance and QT-Interval: Prevalence and Risk Factors—Is It Effective to Switch Therapy to Levomethadone?

Methadone Maintenance and QT-interval: Prevalence and Risk Factors. Is it Effective to Switch Therapy to Levomethadone?

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