Adverse Events During Treatment Induction With Injectable Diacetylmorphine and Hydromorphone for Opioid Use Disorder.
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ABSTRACT: Objectives
The present study aims to describe a 3-day induction protocol for injectable hydromorphone (HDM) and diacetylmorphine (DAM) used in 3 Canadian studies and examine rates of opioid-related overdose and somnolence during this induction phase.Methods
The induction protocol and associated data on opioid-related overdose and somnolence are derived from 2 clinical trials and one cohort study conducted in Vancouver and Montreal (2005-2008; 2011-2014; 2014-2018). In this analysis, using the Medical Dictionary for Regulatory Activities coding system we report somnolence (ie, drowsiness, sleepiness, grogginess) and opioid overdose as adverse events. Overdoses requiring intervention with naloxone are coded as severe adverse events.Results
Data from the 3 studies provides a total of 1175 induction injections days, with 700 induction injection days for DAM, and 475 induction injection days for HDM. There were 34 related somnolence and adverse event (AE) overdoses (4.899 per 100 injection days) in DAM and 6 (1.467 per 100 days) in HDM. Four opioid overdoses requiring naloxone (0.571 per 100 injection days) were registered in DAM and 1 in HDM (0.211 per 100 injection days), all safely mitigated onsite. The first week maximum daily dose patients received were on average 433.62?mg [standard deviation (SD)?=?137.92] and 223.26?mg (SD?=?68.06) for DAM and HDM, respectively.Conclusions
A 3-day induction protocol allowed patients to safely reach high doses of injectable hydromorphone and diacetylmorphine in a timely manner. These findings suggest that safety is not an evidence-based barrier to the implementation of treatment with injectable hydromorphone and diacetylmorphine.
SUBMITTER: Oviedo-Joekes E
PROVIDER: S-EPMC6791495 | biostudies-literature | 2019 Sep/Oct
REPOSITORIES: biostudies-literature
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Project description:Opioid use disorder (OUD) is a significant health problem in the United States and many other countries. A combination of issues, most notably increased prescription of opioid analgesics, has resulted in climbing rates of opioid abuse and overdose over the last decade. This ongoing epidemic has produced a growing population of patients requiring treatment for OUD. Medications such as methadone and buprenorphine have well documented success rates in treating the disorder compared with placebo. However, significant percentages of the population still fail to maintain abstinence or reduce illicit opioid use while using such medications. Genetic variation may play a role in this variability in outcome through pharmacokinetic or pharmacodynamic effects on OUD medications, or by affecting the rate of negative side effects and adverse events. This review focuses on the existing literature on the pharmacogenetics of OUD treatment, with specific focus on medication metabolism, treatment outcomes, and adverse events.
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Project description:BackgroundTo test whether there are gender differences in treatment outcomes among patients receiving injectable opioids for the treatment of long-term opioid-dependence. The study additionally explores whether men and women have different perceptions of treatment effectiveness.MethodsThis study is a secondary analysis from SALOME, a double-blind, phase III, randomized controlled trial testing the non-inferiorirty of injectable hydromorphone to injectable diacetylmorphine among 202 long-term street opioid injectors in Vancouver (Canada). Given this was a secondary analysis, no a priori power calaculation was conducted. Differences in baseline characteristics and six-month treatment outcomes (illicit heroin use, opioid use, crack cocaine use, non-legal activities, physical and psychological health scores, urine positive for street heroin markers, and retention) were analysed by gender using fitted models. Responses to an open ended question on reasons for treatment effectiveness were explored with a thematic analysis.ResultsMen and women differed significantly on a number of characteristics at baseline. For example, women were significantly younger, presented to treatment with significantly higher rates of prior month sex work (31.5% vs. 0%), and used significantly more crack cocaine (14.71 vs. 8.38 days). After six-months of treatment there were no significant differences in treatment outcomes by gender, after adjusting for baseline values. For both men and women, improved health and quality of life were the most common reasons provided for treatment effectiveness, however women were more specific in the types of health improvements.ConclusionsDespite presenting to treatment with vulnerabilities not faced to the same extent by men, at six-months women did not differ significantly from men in tested trial efficacy outcomes. While the primary outcome in the trial was the reduction of illicit opioid use, in the open-ended responses both men and women focused their comments on improvement in health and quality of life as reasons for treatment effectiveness. The supervised model of care with injectable medications provides a particularly suitable framework for providing care to opioid-dependent men and women not attracted or retained by other treatments. The absence of statistical differences reported in this secondary analysis may be due to lack of adequate statistical power to detect meaningful effects.Trial registrationThis trial is registered with ClinicalTrials.gov (NCT01447212) Registered: October 4, 2011 at the following link: https://clinicaltrials.gov/ct2/show/NCT01447212 .
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