Dataset Information

Changes in Mortality Involving Extended-Release and Long-Acting Opioids After Implementation of a Risk Evaluation and Mitigation Strategy.

ABSTRACT:

Objective

To assess changes in mortality rates in extended-release and long-acting (ER/LA) opioid analgesics after the implementation of the Risk Evaluation and Mitigation Strategy (REMS).

Setting

All drug poisoning deaths in three states: Florida, Oregon, and Washington. Data were obtained through state vital records offices and the Researched Abuse, Diversion and Addiction-Related Surveillance System Medical Examiner Program.

Methods

Using cause-of-death literal text from death certificates, individual opioid active pharmaceutical ingredients (APIs) involved in each death were identified using rules-based natural language processing. Population-adjusted and prescriptions dispensed-adjusted mortality rates were calculated for all ER/LA opioid analgesic and individual opioid APIs. Rates before and after implementation of the REMS were compared. Rate changes were compared with rates from two APIs with little or no inclusion in the REMS: benzodiazepines and hydrocodone.

Results

The mean ER/LA opioid analgesic population-adjusted mortality rate significantly decreased in all three states (FL: P?=?0.003; OR: P?=?0.003; WA: P?ConclusionsThe population-adjusted mortality rate of ER/LA opioid analgesics has decreased in three states. Notably, the contributions to mortality rates by individual opioid analgesics were not uniform across the three states in this study. However, these changes were not generally distinct from changes in mortality rates where comparator substances were involved.

SUBMITTER: Black JC

PROVIDER: S-EPMC6953333 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

Changes in Mortality Involving Extended-Release and Long-Acting Opioids After Implementation of a Risk Evaluation and Mitigation Strategy.

Black Joshua C JC Bau Gabrielle E GE Rosen Travis T Cepeda M Soledad MS Wedin Gregory P GP Green Jody L JL Dart Richard C RC

Pain medicine (Malden, Mass.) 20200101 1

<h4>Objective</h4>To assess changes in mortality rates in extended-release and long-acting (ER/LA) opioid analgesics after the implementation of the Risk Evaluation and Mitigation Strategy (REMS).<h4>Setting</h4>All drug poisoning deaths in three states: Florida, Oregon, and Washington. Data were obtained through state vital records offices and the Researched Abuse, Diversion and Addiction-Related Surveillance System Medical Examiner Program.<h4>Methods</h4>Using cause-of-death literal text from ...[more]

PMID: 30877807

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Project description:AimsTo examine perceptions of extended-release (XR) buprenorphine injections among people who regularly use opioids in Australia.DesignCross-sectional survey prior to implementation. XR-buprenorphine was registered in Australia in November 2018.SettingSydney, Melbourne and Hobart. Participants A total of 402 people who regularly use opioids interviewed December 2017 to March 2018.MeasurementsPrimary outcome concerned the proportion of participants who believed XR-buprenorphine would be a good treatment option for them, preferred weekly versus monthly injections and perceived advantages/disadvantages of XR-buprenorphine. Independent variables concerned the demographic characteristics and features of current opioid agonist treatment (OAT; medication-type, dose, prescriber/dosing setting, unsupervised doses, out-of-pocket expenses and travel distance).FindingsSixty-eight per cent [95% confidence interval (CI) = 63-73%] believed XR-buprenorphine was a good treatment option for them. They were more likely to report being younger [26-35 versus > 55 years; odds ratio (OR) = 3.16, 95% CI = 1.12-8.89; P = 0.029], being female (OR = 1.67, 95% CI = 1.04-2.69; P = 0.034), < 10 years school education (OR = 1.87, 95% CI = 1.12-3.12; P = 0.016) and past-month heroin (OR = 1.81, 95% CI = 1.15-2.85; P = 0.006) and methamphetamine use (OR = 1.90, 95% CI = 1.20-3.01; P = 0.006). Fifty-four per cent reported no preference for weekly versus monthly injections, 7% preferred weekly and 39% preferred monthly. Among OAT recipients (n = 255), believing XR-buprenorphine was a good treatment option was associated with shorter treatment episodes (1-2 versus ≥ 2 years; OR = 3.93, 95% CI = 1.26-12.22; P = 0.018), fewer unsupervised doses (≤ 8 doses past-month versus no take-aways; OR = 0.50; 95% CI = 0.27-0.93; P = 0.028) and longer travel distance (≥ 5 versus < 5 km; OR = 2.10, 95% CI = 1.20-3.65; P = 0.009). Sixty-nine per cent reported 'no problems or concerns' with potential differences in availability, flexibility and location of XR-buprenorphine.ConclusionsAmong regular opioid users in Australia, perceptions of extended-release buprenorphine as a good treatment option are associated with being female, recent illicit drug use and factors relating to the (in)convenience of current opioid agonist treatment.

Project description:ImportanceTransmucosal immediate-release fentanyls (TIRFs), indicated solely for breakthrough cancer pain in opioid-tolerant patients, are subject to a US Food and Drug Administration (FDA) Risk Evaluation and Mitigation Strategy (REMS) to prevent them from being prescribed inappropriately.ObjectivesTo evaluate knowledge assessments of pharmacists, prescribers, and patients regarding appropriate TIRF use; to describe sponsor assessments, based on claims data, of whether the REMS program was meeting its goals; and to characterize how the FDA responded to REMS assessments.Design, setting, and participantsQualitative analysis of 4877 pages of FDA documents obtained through a Freedom of Information Act request, including 6 annual REMS assessment reports (2012-2017), FDA evaluations of these reports, and FDA-sponsor correspondence about safety issues.ExposureA REMS program to reduce the risk of adverse outcomes, including misuse, abuse, addiction, and overdose, arising from use of TIRFs.Main outcomes and measures(1) Knowledge assessments of pharmacists, prescribers, and patients; (2) survey and claims-based prescribing assessments; (3) FDA and TIRF sponsor communications; (4) modifications to the REMS program; and (5) disenrollment of noncompliant prescribers.ResultsTwelve months after initiation of the program, 24 of 302 pharmacists (7.9%), 35 of 302 prescribers (11.6%), and 5 of 192 patients (2.6%) incorrectly reported that TIRFs can be prescribed to opioid-nontolerant patients, with similar levels of misunderstanding maintained in the subsequent reports. At 60 months, product-specific analyses of claims data indicated that between 34.6% and 55.4% of patients prescribed TIRFs were opioid-nontolerant. In the 48-month survey, 106 of 310 prescribers (34.2%) reported prescribing TIRFs for opioid-tolerant patients with chronic, noncancer pain; at 60 months, 54 of 302 prescribers (18.4%) and 148 of 310 patients (47.7%) erroneously reported that TIRFs were FDA-approved for such use. Over the 60-month period examined, there were few substantive changes made to the REMS to address evidence of high rates of off-label TIRF use, and, although the REMS program had a noncompliance plan, there was no report of prescribers being disenrolled for inappropriate prescribing.Conclusions and relevanceIn this review of FDA documents pertaining to the TIRF REMS, surveys of pharmacists, prescribers, and patients reflected generally high levels of knowledge regarding proper TIRF prescribing, yet some survey items as well as claims-based analyses indicated substantial rates of inappropriate TIRF use. Despite these findings, the FDA did not require substantive changes to the program.

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Project description:Background and objectivesThe effectiveness and tolerability of tapentadol extended release (ER), a centrally acting analgesic with μ-opioid receptor agonist and norepinephrine (noradrenaline) reuptake inhibitor activities, have been demonstrated in patients with chronic pain, including those switching directly from prior opioid therapy. The objective of the current study was to evaluate the effectiveness and safety of conversion to oral tapentadol ER (50-250 mg twice daily) from previous around-the-clock strong opioid therapy in patients with moderate to severe, chronic malignant tumor-related cancer pain that was well-controlled.MethodsThis randomized, open-label, phase III study, which was conducted in Japan, included a 1- to 2-week screening period (on previous opioid) and an 8-week, open-label treatment period. Eligible patients, who were taking a strong opioid analgesic and had a mean pain intensity score <4 during the 3 days prior to randomization (adequate pain control on previous strong opioid), were randomized (1:1) to receive twice-daily treatment with tapentadol ER (100-500 mg/day) or morphine sustained release (SR; 20-140 mg/day; reference for assay sensitivity). Initial doses were estimated based on the conversion ratio of tapentadol ER:oxycodone:morphine:fentanyl = 10:2:3:0.03. The primary effectiveness endpoint was the proportion of patients who maintained pain control [change from baseline in mean pain intensity (11-point numerical rating scale) less than +1.5 for 3 consecutive days and no more than two doses of rescue medication per day for 3 consecutive days) during the first week of open-label treatment.ResultsIn the tapentadol ER group (n = 50), 84.0 % of patients (42/50; 95 % CI, 70.89-92.83) maintained pain control during Week 1. On the Patient Global Impression of Change, 2.1 % (1/48), 2.1 % (1/48), 22.9 % (11/48), and 50.0 % (24/48) of patients in the tapentadol ER group reported that their overall condition was "very much improved," "much improved," "minimally improved," and "not changed," respectively, at Week 1 compared with 0 %, 10.7 % (3/28), 28.6 % (8/28), and 53.6 % (15/28) reporting these ratings at Week 8. The sensitivity of effectiveness analyses was validated based on results using morphine SR; 98.0 % (49/50; 95 % CI, 89.35-99.95) of patients in the morphine SR group maintained pain control after 1 week of treatment. The overall safety profile was similar to that demonstrated in previous studies; tapentadol ER was associated with a lower incidence of gastrointestinal treatment-emergent adverse events than morphine SR [38.0 % (19/50) vs. 54.0 % (27/50)], including constipation [12.0 % (6/50) vs. 20.0 % (10/50)] and vomiting [6.0 % (3/50) vs. 26.0 % (13/50)].ConclusionsOverall, results indicate that conversion from previous strong opioids to tapentadol ER (50-250 mg twice daily) was successful and resulted in safe and effective pain control with improved gastrointestinal tolerability versus morphine SR in patients with moderate to severe cancer-related pain that was well-controlled on their previous opioid.

Dataset Information

Changes in Mortality Involving Extended-Release and Long-Acting Opioids After Implementation of a Risk Evaluation and Mitigation Strategy.

Objective

Setting

Methods

Results

Publications

Changes in Mortality Involving Extended-Release and Long-Acting Opioids After Implementation of a Risk Evaluation and Mitigation Strategy.

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