Department of Pharmacy, Tan Tock Seng Hospital, Singapore.
Palliative Care Centre for Excellence in Research and Education, Singapore.
BMJ Support Palliat Care. 2022 Dec;12(e6):e736-e739. doi: 10.1136/bmjspcare-2019-002175. Epub 2020 Apr 22.
Methadone is a useful option in the treatment of cancer pain. Despite its advantages, methadone use is complicated due to high interindividual variability in pharmacokinetics. Various rotation methods from other opioids have been proposed in mostly Caucasian populations.
This study aims to describe our experience with opioid rotation to methadone for management of cancer pain in a predominantly Asian population.
A retrospective review of 52 inpatients initiated on methadone for cancer pain from June 2015 to June 2018 was conducted. Our institution protocol for methadone rotation involves either one of two methods ('Stop-and-go' or the Edmonton 3-day rotation) based on the morphine-equivalent daily dose (MEDD), using an equianalgesic ratio of 10:1 for MEDD <1000 mg. To account for incomplete cross-tolerance, we further reduce the calculated dose by 30%.
The majority of patients had mixed nociceptive-neuropathic pain (83%) and the predominant reason for methadone rotation was ineffective analgesia with other opioids (75%). The median MEDD before rotation was 104 mg. Effective analgesia (defined as a decrease in numerical rating scale (NRS) of ≥1 or attainment of NRS ≤3) was achieved within 3 days after rotation in 89% of patients. Patients with an MEDD ≤100 mg/day required a greater degree of uptitration of methadone dose after rotation compared with those with an MEDD >100 mg/day.
Rotation to methadone according to our protocol is effective in achieving adequate analgesia in most patients experiencing nociceptive-neuropathic pain. Our results also suggest that a fixed equianalgesic ratio of 10:1 may be adequate for patients at low-to-moderate MEDD <400 mg/day.
美沙酮是治疗癌痛的有效选择。尽管具有优势，但由于药代动力学个体间的高度变异性，美沙酮的使用较为复杂。在主要为白种人群体中，已经提出了各种从其他阿片类药物转换的方法。
本研究旨在描述我们在以亚洲人为主的人群中，使用美沙酮治疗癌痛的经验，主要涉及从其他阿片类药物转换为美沙酮的方法。
对 2015 年 6 月至 2018 年 6 月期间因癌痛而开始接受美沙酮治疗的 52 例住院患者进行回顾性分析。我们机构的美沙酮转换方案根据吗啡等效日剂量（MEDD），采用 10:1 的等痛觉效应比，选择“停走法”或埃德蒙顿 3 天转换法中的一种方法，当 MEDD<1000mg 时。为了考虑不完全交叉耐受，我们进一步将计算剂量减少 30%。
大多数患者存在混合伤害感受性-神经性疼痛（83%），因其他阿片类药物无效而进行美沙酮转换是主要原因（75%）。转换前 MEDD 的中位数为 104mg。89%的患者在转换后 3 天内达到有效镇痛（定义为数字评分量表（NRS）下降≥1 或达到 NRS≤3）。与 MEDD>100mg/天的患者相比，MEDD≤100mg/天的患者在转换后需要更大程度地增加美沙酮剂量。
根据我们的方案，大多数患有伤害感受性-神经性疼痛的患者，转换为美沙酮后能够实现充分的镇痛。我们的结果还表明，对于 MEDD<400mg/天的低至中度 MEDD 的患者，10:1 的固定等效比可能是足够的。
