Takemura Miho, Niki Kazuyuki, Okamoto Yoshiaki, Matsuda Yoshinobu, Ueda Mikiko, Uejima Etsuko
Department of Clinical Pharmacy Research and Education, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
Department of Pharmacy, Ashiya Municipal Hospital, Ashiya, Japan.
JMA J. 2020 Jul 15;3(3):258-264. doi: 10.31662/jmaj.2019-0039. Epub 2020 Jul 7.
The Japanese packaging instructions for methadone prohibit dose escalation within 7 days of administration initiation as this may result in overdose and subsequent adverse events. However, for terminal cancer patients, evaluation of the effects of methadone may be desirable within 7 days because they have limited prognoses. We aimed to determine the possibility of estimating the adequateness of methadone earlier than the 7th day by investigating the onset timing of analgesic effects and adverse events of methadone in Japanese terminal cancer patients.
Japanese terminal cancer patients who started taking methadone in Ashiya Municipal Hospital were enrolled from January 1, 2013 to February 28, 2019. Verbal rating scale (VRS) scores on pain and adverse events before and after methadone administration (on days 3, 5, and 7) were retrospectively investigated from medical records.
We enrolled 25 patients, of which 20 (80.0%) received methadone until day 7. The VRS score (mean ± standard deviation) on pain was significantly reduced to 0.90 ± 0.55 on day 3, compared with 1.65 ± 0.67 before the administration of methadone (p < 0.05). The mean VRS scores did not differ significantly on days 3, 5, and 7. Additionally, of the 23 patients who received methadone until day 3, 20 (87.0%) showed an analgesic effect on day 3 and 17 (85.0%) received methadone without experiencing serious adverse events until day 7.
The adequateness of methadone in Japanese terminal cancer patients could be determined before day 7, considering the high analgesia incidence and few adverse events 3 days after the methadone administration under careful observation by a physician experienced in methadone administration. However, as this is a preliminary study, the relationship between pharmacokinetic parameters and analgesic effects was not evaluated. Further studies involving pharmacokinetics and multicenter prospective studies are required to support these findings.
美沙酮的日本包装说明书禁止在开始给药的7天内增加剂量，因为这可能导致过量用药及随后的不良事件。然而，对于晚期癌症患者，由于其预后有限，可能需要在7天内评估美沙酮的效果。我们旨在通过调查日本晚期癌症患者中美沙酮镇痛效果和不良事件的起效时间，确定在第7天之前更早估计美沙酮是否合适的可能性。
2013年1月1日至2019年2月28日期间，纳入在芦屋市立医院开始服用美沙酮的日本晚期癌症患者。从医疗记录中回顾性调查美沙酮给药前及给药后（第3、5和7天）的疼痛和不良事件的视觉模拟评分（VRS）。
我们纳入了25例患者，其中20例（80.0%）服用美沙酮至第7天。与美沙酮给药前的1.65±0.67相比，第3天疼痛的VRS评分（平均值±标准差）显著降至0.90±0.55（p<0.05）。第3、5和7天的平均VRS评分无显著差异。此外，在23例服用美沙酮至第3天的患者中，20例（87.0%）在第3天显示出镇痛效果，17例（85.0%）服用美沙酮至第7天未发生严重不良事件。
在有美沙酮给药经验的医生仔细观察下，考虑到美沙酮给药3天后镇痛发生率高且不良事件少，日本晚期癌症患者中美沙酮的合适剂量可在第7天之前确定。然而，由于这是一项初步研究，未评估药代动力学参数与镇痛效果之间的关系。需要进一步开展涉及药代动力学的研究和多中心前瞻性研究来支持这些发现。
