Lifetree Clinical Research and Pain Clinic, Salt Lake City, Utah 84106, USA.
J Pain Symptom Manage. 2010 Nov;40(5):734-46. doi: 10.1016/j.jpainsymman.2010.05.004.
Morphine sulfate and naltrexone hydrochloride extended release capsules contain extended-release pellets of morphine with a sequestered naltrexone core (MS-sNT). Taken whole, as intended, morphine is released to provide pain relief; if tampered with by crushing, naltrexone is released to mitigate subjective effects of morphine.
This open-label study assessed long-term (12-month) safety of MS-sNT in patients with chronic, moderate to severe pain.
Safety assessments included determining adverse events (AEs), laboratory assessments, and the Clinical Opiate Withdrawal Scale (COWS). Analgesic efficacy was assessed (diary) as worst, least, average, and current pain using an 11-point numeric scale (0=none; 10=worst).
Of 465 patients receiving one or more doses, 160 completed the study. Most patients (81.3%) experienced one or more AEs, most commonly constipation (31.8%) or nausea (25.2%). Thirty-three patients (7.1%) reported serious AEs; one patient's severe gastrointestinal inflammation and colitis were considered possibly study drug-related. Most discontinuations (30%) occurred in the first month, most often because of AEs (23.7%). There were no clinically relevant changes in laboratory results or vital signs, and no clinically significant electrocardiogram changes deemed study drug-related. During each visit after Week 1, 5% or fewer patients had COWS scores indicating mild withdrawal symptoms (range, 0%-4.8%). Five patients, who did not take the study drug as instructed, had scores consistent with moderate withdrawal. MS-sNT yielded statistically significant improvements from baseline in mean scores for all pain diary items for all visits, except Week 1 for least pain.
In this study population, when MS-sNT was taken as directed for chronic, moderate to severe pain for up to 12 months, most AEs were typical opioid-related side effects. Mean COWS scores remained low, indicating lack of withdrawal symptoms and appropriate transition off the study drug at completion.
硫酸吗啡和盐酸纳曲酮缓释胶囊含有包被纳曲酮核心的缓释吗啡丸（MS-sNT）。如果整片吞服，即按规定服用，吗啡会被释放以缓解疼痛；如果被压碎，纳曲酮就会被释放以减轻吗啡的主观作用。
本开放性研究评估了慢性、中重度疼痛患者接受 MS-sNT 治疗 12 个月的长期安全性。
安全性评估包括确定不良事件（AE）、实验室评估和临床阿片戒断量表（COWS）。使用 11 点数字评分（0=无；10=最差）评估镇痛疗效（日记）：最差、最小、平均和当前疼痛。
在接受过一次或多次剂量的 465 名患者中，有 160 名完成了研究。大多数患者（81.3%）经历了一次或多次 AE，最常见的是便秘（31.8%）或恶心（25.2%）。33 名患者（7.1%）报告了严重 AE，1 名患者的严重胃肠道炎症和结肠炎被认为可能与研究药物有关。大多数停药（30%）发生在第一个月，最常见的原因是 AE（23.7%）。实验室结果或生命体征无临床相关变化，无临床意义的心电图变化被认为与研究药物相关。在第 1 周后的每次就诊中，有 5%或更少的患者的 COWS 评分显示轻度戒断症状（范围为 0%-4.8%）。5 名未按规定服用研究药物的患者的评分与中度戒断一致。在所有就诊中，除了第 1 周的最小疼痛外，MS-sNT 均使所有疼痛日记项目的平均评分从基线显著改善。
在该研究人群中，当 MS-sNT 用于慢性、中重度疼痛时，按规定服用长达 12 个月，大多数 AE 是典型的阿片类药物相关副作用。平均 COWS 评分仍然较低，表明无戒断症状，并且在完成时适当过渡到停用研究药物。
