Extended-release Opioids Research Articles

Development and implementation of autoverification standardization in the adult and pediatric emergency department.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. This project utilized the guidance of the American Society of Health-System Pharmacists (ASHP) autoverification toolkit to refine our health system's approach to autoverification and contribute to the literature regarding appropriate use of autoverification technology in a pediatric and adult emergency department (ED). This single-center quality improvement study was conducted in an academic medical center ED that has 33 pediatric beds and 77 adult beds. A team consisting of clinical pharmacy specialists in emergency medicine, medication safety and informatics personnel, operational managers, and pharmacy leadership was identified to develop and implement autoverification best practices in the ED utilizing practices outlined within the ASHP autoverification toolkit. Before implementation of best practices, defined as the "preoptimization" state, autoverification took place for most medications available in the automated dispensing cabinets (ADCs). By anchoring the autoverification rule on ADC inventory, it was challenging to optimize both inventory practices and autoverification best practices. This project focused on redesigning the autoverification rules in the electronic health record, defined as the "postoptimization" state. In the postoptimization state, autoverification in the ED was updated to better align with regulatory standards. Autoverification metrics and the percentage of orders that autoverified vs required pharmacist verification were analyzed in the preoptimization and postoptimization states. This project utilized the guidance from ASHP's autoverification toolkit to refine our health system's approach to autoverification. High-alert medications (eg, insulin, extended-release opioids, digoxin) were taken off autoverification following implementation. Optimization of autoverification rules allows more orders for high-alert medications to be reviewed by a pharmacist.

Inpatient Use of Extended-Release (ER) Opioids for Vaso-Occlusive Crisis Associated with Increased Length of Stay for ER Opioid-Naïve Patients

Background: The intermittent acute pain syndrome associated with sickle cell disease (SCD) is a poorly understood phenomenon with complex pathophysiology. Given the broad spectrum of analgesic interventions, including immediate-release (IR) and extended-release (ER) opioids, healthcare providers are challenged with the task of safely and effectively escalating inpatient opioid regimens, especially in the setting of limited guidelines outlining the combination of different opioid formulations. Despite SCD being the most common genetic disorder in the United States, more research is required to improve physician expertise with appropriate and timely pain management of vaso-occlusive crisis. Methods: This study was a retrospective chart review (n=200) of patients with known SCD requiring hospitalization for acute pain secondary to vaso-occlusive crisis without an alternative etiology of pain symptoms. The review included a patient population aged 18-67 years old with 43.5% males and 56.5% females hospitalized from 2/1/2022 to 5/6/2022. The primary outcome measure was hospital length of stay (LOS) for adequate pain control compared against varying factors of inpatient opioid-prescribing practices, including initiation or continuation (if prescribed within 6 months prior to admission encounter per PDMP review) of an ER opioid formulation, degree of morphine milligram equivalents (MME) escalation from outpatient regimen, utilization of a sickle cell analgesic order set, and initiation of patient-controlled analgesia pump (PCA). A secondary outcome measure investigated was the quantitative comparison of highest daily prescribed MME in relation to the aforementioned inpatient variables. Data analysis was completed using Wilcoxon Rank Summary analysis, with a significant p-value set to < 0.05. Results: Among the primary outcome analysis, the only significant factor affecting LOS was the introduction of an ER opioid. The results show that within the patient cohort naïve to an outpatient ER opioid (n=105), ER opioid-incorporated inpatient analgesic regimens resulted in a significantly increased mean LOS compared to IR opioid monotherapy regimens, with an average of 8.8 inpatient days as compared to 5.3 days, respectively (p-value < 0.001). For the patients prescribed an outpatient ER opioid at baseline (n=95), the continuation of an inpatient ER opioid did not result in a significant change in mean LOS, calculated as 6.7 days vs. 6.0 days in the continued and non-continued groups, respectively (p-value = 0.716). Among the secondary outcome measures, utilization of a sickle cell order set and PCA did not significantly affect degree of MME escalation. Conclusions: Limited evidence-based recommendations for the treatment of acute pain episodes in SCD has resulted in widely varying opioid regimens prescribed by inpatient providers and has created clinical challenges regarding the optimization of pain management. This study investigated inpatient opioid regimens utilized in treatment of vaso-occlusive crisis and found that the initiation of ER opioids resulted in increased length of stay for ER opioid-naïve patients as compared to treatment with IR opioids alone. These results question the benefit of inpatient ER opioids in relation to the risk of opioid dependence and MME escalation.

Differences in severity of poison centers exposures involving XTAMPZA® ER versus other opioid analgesics.

Aims: Xtampza® ER (Collegium Pharmaceutical, MA, USA) is an abuse-deterrent formulation (ADF) of oxycodone intended to deter tampering for use by unintended routes of administration. We assessed whether Xtampza ER exposures were less likely to result in severe medical outcomes relative to other opioid analgesic exposures. Materials & methods: Exposures reported to participating poison centersbetween2016 and2021 inclusivethat were followed to a known medical outcome were analyzed. Xtampza ER was compared with other ADF opioids, non-ADF extended-release opioids, single-entity oxycodone immediate-release, unspecified oxycodoneand unspecified morphine. Results & conclusion: No Xtampza ER exposures involved unintended routes of administration. Xtampza ER exposures were less likely to be abuse, misuse or suspected suicidal, and medical outcomes were less severe than comparators.

A Cross-Sectional Study of Tampering in Xtampza ER, an Abuse-Deterrent Formulation of an Extended-Release Opioid, in a Treatment Center Population.

While the current landscape of opioid use disorder (OUD) is complicated by the increase in use of non-prescription opioids, prescription opioids continue to be frequently used in non-medical ways. In response to this abuse, pharmaceutical companies have developed abuse deterrent formulations (ADFs) for extended-release (ER) opioids. To test the effectiveness of Xtampza ER ADF (oxycodone myristate) at reducing tampering, its rate of tampering in a treatment-center population was compared to immediate release (IR) single entity (SE) oxycodone, other ER oxycodone opioids, and ER oxymorphone. Data were collected between the third quarter of 2018 and the third quarter of 2021 from individuals entering nationally distributed opioid treatment programs. To determine odds of tampering with Xtampza ER compared to each comparator, a logistic model was fit with a random intercept allowing for multiple drugs in each subject. Within-subject correlation was assumed to have a compound symmetric relationship. Overlap among the categories of drug tampering was high. Logistic regression analyses found that oxycodone myristate had lower odds of tampering when compared to both IR SE oxycodone (OR = 0.23 [95% CI0.11, 0.50], p = 0.0002) and ER oxymorphone (OR = 0.30 [95% CI0.14, 0.67], p = 0.0038). Oxycodone myristate was not significantly different from other ER oxycodone opioids (OR = 0.5 [95% CI0.24, 1.03], p = 0.0612). These findings did not change when the estimates were adjusted for age and sex. Drugs employing ADF technology may reduce the likelihood of tampering when compared to non-ADF formulations in a treatment-center population, which represents an opportunity for intervention in OUD among those still requiring pain management.

Determinants of satisfaction with acute pain therapy during and after childbirth.

An important task in obstetrics is to offer patients adequate pain management after vaginal delivery (VD) and after cesarean section (CS). The aim of the present analysis was to assess pain intensity at the day after childbirth, after 3 and 6 months in women after VD and after CS. Additionally, it was planned to identify determinants of maternal satisfaction with acute pain therapy following VD and CS. This secondary analysis of asingle-center prospective cohort study included 210 parturients. The women gave birth in the University Hospital of Wuerzburg. They completed asurvey before childbirth(P), on the first day (D1), 3and 6months after VD and CS. The survey included questions about the expected pain, the experienced pain, the birth, the pain afterwards and also psychological questionnaires. In addition, information was collected from the patient records. Women with planned CS received spinal anesthesia. Asecondary CS was performed with an epidural, spinal or general anesthesia. Pain therapy on the ward was standardized. The primary outcomes were acute and chronic pain intensity at rest, during movement, determinants of satisfaction with pain therapy and the wish to have received more pain medication during and after VD and CS (D1). A total of 175women completed the survey at all time points and were available for the analysis (drop-out 16.8%). The results confirmed high pain levels at D1 after CS (median pain intensity during movement: 8NRS points, interquartile range, IQR 6-9 points). After VD pain scores were much lower (median pain intensity during movement:4 points, IQR 2-5 points). Of the mothers 7.4% reported pain at rest at all time points after VD or CS but pain intensity was low after3 and 6months (median pain intensity at rest:2 points, IQR 0-3 points), 28% received extended-release opioids after CS and 33% of women (VD and CS) had an epidural. The most important influencing factor for lower satisfaction with pain therapy after CS or VD was inadequate pain relief. Women with VD who had an epidural, were more satisfied during delivery than women without but there was no difference at D1. This study confirmed high acute pain levels following CS and an incidence of chronic pain of around 7% but pain intensity was low and one third received strong opioids after CS. Around 11% of women after primary CS (8% epidural, 3% combined spinal/epidural) and around 55% of women after secondary CS had an epidural, which could be used for pain therapy after birth. Women without an epidural or without opioids may not have had good pain management. The received pain relief appeared to be the most relevant predictor for satisfaction and the wish to have received more pain medication. Mothers having aVD with an epidural catheter were more satisfied with pain therapy during birth than those without. Therefore, abetter multimodal pain management (including opioids, epidural and nonopioids) might provide better pain relief and might improve overall satisfaction with pain treatment following CS. Finally, the received pain relief might be abetter patient-related outcome measure for satisfaction with pain treatment after childbirth than pain intensity alone.

Opioid prescribing practices in trauma patients at discharge: An exploratory retrospective chart analysis.

This study examined the opioid prescribing patterns at discharge in the trauma center of a major Canadian hospital and compared them to the guidelines provided by the Illinois surgical quality improvement collaborative (ISQIC), a framework that has been recognized as being associated with reduced risk.This was a retrospective chart review of patient data from the trauma registry between January 1, 2018, and October 31, 2019. A total of 268 discharge charts of naïve opioid patients were included in the analysis. A Morphine Milligram Equivalents per day (MME/day) was computed for each patient who was prescribed opioids and compared with standard practice guidelines.About 75% of patients were prescribed opioids. More males (75%) than females (25%) were prescribed opioids to patients below 65 years old (91%). Best practice guidelines were followed in most cases. Only 16.6% of patients were prescribed over 50 mg MME/day, the majority (80.9%) were prescribed opioids for =<3 days and only 1% for >7 days. Only 7.5% were prescribed extended-release opioids and none were strong like fentanyl. Patients received a multimodal approach with alternatives to opioids in 88.9% of cases and 82.9% had a plan for opioid discontinuation. However, only 23.6% received an acute pain service referral.The majority of the prescriptions provided adhered to the best practice guidelines outlined by the ISQIC framework. These results are encouraging with respect to the feasibility of implementing opioid prescription guidelines effectively. However, routine monitoring is necessary to ensure that adherence is maintained.

Opioid Utilization and Management in the Setting of Stewardship During Inpatient Rehab Care.

BackgroundOpioid utilization and management in an inpatient rehabilitation setting have not been widely described, despite the unique opportunities that exist in this setting to support opioid stewardship across transitions in care. We aimed to characterize opioid utilization and management by interprofessional teams across a large, inpatient rehabilitation setting after incorporation of opioid stewardship principles by pharmacists as part of their daily practice.Patients and methodsThis was a retrospective chart review at Toronto Rehab, University Health Network, Toronto, Canada. Patients with admission orders for any opioid from November 2017 to February 2018 were included. Complex continuing care and palliative care patients were excluded. Descriptive statistics were primarily used to describe the data as well as univariate linear regression to compare associations with milligram morphine equivalent (MME) reduction.ResultsA total of 448 patients were included. A reduction in total daily MME was seen in 49% (n=219) of the patients during their inpatient stay, with 73% (n=159) of these patients having a reduction of ≥50%. Sixty-nine percent (n=311) of the patients received an opioid prescription at discharge, with most scheduled (90%, n=98) with a supply of less than 30 days. Rehabilitation length of stay was correlated with a MME decrease during rehab (p<0.01), suggesting that longer lengths of stay contributed to a greater reduction in MME. Patients with chronic opioid use prior to acute care admission (p=0.01), and those who started extended-release opioids during acute care (p=0.02) were significantly less likely to discontinue opioids during rehab stay.ConclusionOpioid utilization and management in the setting of opioid stewardship across inpatient rehab and transitions of care were characterized. Opportunities exist for further quality improvement initiatives within inpatient rehabilitation and acute care settings to identify and support patients with complex pain management needs.

Association of 3 CDC opioid prescription guidelines for chronic pain and 2 payer pharmacy coverage changes on opioid initiation practices.

BACKGROUND: Due to the US opioid epidemic, in March of 2016, the Centers for Disease Control and Prevention (CDC) published new guidelines for primary care providers on opioid prescribing for chronic pain. Payer coverage changes were also implemented to help modify opioid prescribing behavior. Whether these initiatives were associated with changes in opioid initiation patterns is unknown. OBJECTIVE: To assess the association between 3 of the 2016 CDC guidelines and 2 subsequent payer pharmacy coverage changes with changes in opioid initiation behavior across different provider specialties. METHODS: We conducted a real-world evidence study using claims data from OptumLabs Data Warehouse between January of 2014 and December of 2018. Subjects were continuously enrolled opioid naive patients, aged at least 18 years, who had at least 1 chronic pain diagnosis within 2 weeks before their first (first-time) opioid prescription. The study used multiple treatment period segmented regression analysis to evaluate the association, across different provider specialties, between the CDC guideline release and the payer pharmacy coverage changes with immediate change in level and overall change in the rate of first-time extended-release opioid prescriptions, firsttime opioid prescriptions at doses of at least 50 MME (morphine milligram equivalent) per day, and first-time opioid prescriptions with overlapping benzodiazepine prescription. RESULTS: The CDC guidelines were not associated with any change in the rate of first-time prescriptions of extended-release opioids. However, a January 2017 payer pharmacy coverage change was associated with a reduction over time in first-time extended-release opioid prescription rates by 22.15 in every 100,000 prescriptions (CI = -40.04 to -2.92, P = 0.013). The CDC guidelines were associated with an immediate decline in level of first-time opioid prescription at doses of at least 50 MME per day by 74.00 in every 10,000 prescriptions (CI = -124.86 to -23.13, P = 0.004) and an increased rate of decline over time by 13.64 in every 10,000 prescriptions (CI = -17.07 to -10.21, P < 0.001). These associations varied across provider types and specialties. The March 2018, payer coverage change was associated with an immediate reduction in level of first-time opioid prescriptions at doses of at least 50 MME per day across all specialties and an increased reduction over time among surgeons. The CDC guidelines were associated, respectively, with a reduction in the rate of overlapping first-time opioid prescriptions with benzodiazepines among family medicine, internal medicine, surgeons, emergency medicine providers, and providers with unknown specialty by 6.11, 5.10, 2.89, 11.43, and 9.11 in every 10,000 prescriptions monthly (CI = -9.48 to -2.73, -9.86 to -0.35, -5.40 to -0.38, -17.26 to -5.61 and -11.96 to -6.25, respectively, P < 0.001, P = 0.035, P = 0.024, P < 0.001 and P < 0.001). CONCLUSIONS: Some specialist providers also adopted the CDC guidelines, and the response to the guidelines differed across various provider specialties. Some CDC guidelines were associated with a reduction in high-risk first-time opioid prescriptions. Payer pharmacy coverage changes reinforced the guidelines both in situations where the CDC guidelines did and did not show any association. DISCLOSURE: This research was funded by Agency for Healthcare Research and Quality (R01 HS025164; PI: Karaca-Mandic). Karaca-Mandic reports grants from the American Cancer Society and Sempre Health, along with fees from Tactile Medical and Precision Health Economics, unrelated to this study. The other authors have nothing to disclose.

Impact of an Australian/New Zealand organisational position statement on extended-release opioid prescribing among surgical inpatients: a dual centre before-and-after study.

Extended-release opioids are often prescribed to manage postoperative pain despite being difficult to titrate to analgesic requirements and their association with long-term opioid use. An Australian/New Zealand organisational position statement released in March 2018 recommended avoiding extended-release opioid prescribing for acute pain. This study aimed to evaluate the impact of this organisational position statement on extended-release opioid prescribing among surgical inpatients. Secondary objectives included predictors and clinical outcomes of prescribing extended-release opioids among surgical inpatients. We conducted a retrospective, dual centre, 11-month before-and-after study and time-series analysis by utilising electronic medical records from two teaching hospitals in Sydney, Australia. The primary outcome was the proportion of patients prescribed an extended-release opioid. For surgical patients prescribed any opioid (n = 16,284), extended-release opioid prescribing decreased after the release of the position statement (38.4% before vs. 26.6% after, p < 0.001), primarily driven by a reduction in extended-release oxycodone (31.1% before vs. 14.1% after, p < 0.001). There was a 23% immediate decline in extended-release opioid prescribing after the position statement release (p < 0.001), followed by an additional 0.2% decline per month in the following months. Multivariable regression showed that the release of the position statement was associated with a decrease in extended-release opioid prescribing (OR 0.54, 95%CI 0.50-0.58). Extended-release opioid prescribing was also associated with increased incidence of opioid-related adverse events (OR 1.52, 95%CI 1.35-1.71); length of stay (RR 1.44, 95%CI 1.39-1.51); and 28-day re-admission (OR 1.26, 95%CI 1.12-1.41). Overall, a reduction in extended-release opioid prescribing was observed in surgical inpatients following position statement release.

A retrospective review of the use of oxymorphone immediate release for long term pain control in cancer patients with gastrostomy tubes.

Cancer patients often require feeding or venting gastrostomy-tubes (G-tubes) for enteral nutrition or symptom palliation. The administration of most extended-release (ER) opioids via the G-tube or orally followed by clamping of the venting G-tube is contraindicated. Oxymorphone immediate release (IR) may be useful because of its longer half-life compared to other IR opioids. We examined the use of oxymorphone IR administered every 8 hours in patients with G-tubes. This was a retrospective chart review of 40 consecutive cancer patients with G-tubes who underwent opioid rotation (OR) to oxymorphone. Demographics, symptoms, morphine equivalent daily dose (MEDD), and oxymorphone dose were collected. Successful OR was defined as a 2-point or 30% reduction in pain score and continued use of oxymorphone at follow-up in outpatient setting, or discharge in inpatient setting. Opioid rotation ration (ORR) between MEDD and oxymorphone in patients with successful OR was calculated as MEDD before the OR divided by total oxymorphone dose/day at follow-up or discharge. The median age was 56 years, 57.5% were white, 68% male, 47.5% (n=19) had head and neck cancer, 90% had advanced disease, 67.5% (n=27) were inpatient, and 15% (n=6) had venting G-tubes. 25/40 (62.5%) patients had successful OR to oxymorphone. The median ORR from MEDD to oxymorphone was 3.5 (IQR, 3.1-4). There were no independent predictors for successful OR, and ORR did not significantly differ among various groups. Oxymorphone IR can be used successfully in cancer patients with G-tubes using an ORR of 3.5 to calculate dose from MEDD.

An ethnographic study of opioid use disorder in rural Maine: The problem of pain

This qualitative study was conducted to more fully understand health care providers and community leaders’ perceptions of the opioid crisis in rural Maine. In 2017, Maine continued to have one of the highest opioid overdose death rates in the country, more than double the national average. I (first author) visited eight treatment centers in Maine providing support and treatment to people recovering form Opioid Use Disorder (OUD), shadowing health care providers. I also attended OUD-related meetings held with community leaders. I conducted a total of 33 semi-structured interviews with health care providers, community leaders, and NGOs in the state of Maine. Three themes emerged integrating observations with semi-structured interviews: i) Impact of emergence of new extended release opioids, their prescription patterns, and culture around them; ii) Subjectivity of pain and importance of understanding psychic injury in OUD treatment; iii) Socio-political context and perception of OUD in Maine. Our society’s perception of pain has deep historical and cultural sources that influence the way that pain has been perceived and treated in the medical setting. Resources beyond the medical environment are needed to address pain adequately.

Postmarketing Analysis of Misuse, Abuse, and Diversion of Xtampza ER

ObjectiveTo evaluate abuse, misuse, and diversion of Xtampza ER, an extended-release (ER) abuse-deterrent formulation (ADF) of oxycodone.MethodsAbuse, misuse, and diversion of Xtampza ER were assessed using Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) System data sources. Xtampza ER was compared with immediate-release (IR) oxycodone, other ADF ER products combined, and non-ADF ER products combined.ResultsXtampza ER prescriptions increased 50-fold during the study period. In contrast, cases from poison centers, substance abuse treatment centers, and diversion were infrequent and did not increase. Adjusted for prescriptions dispensed, poison center exposures were greater for IR oxycodone (rate ratio [RR] = 2.3, P = 0.008), other ADF ER opioids (RR = 5.2, P < 0.001), and non-ADF ER opioids (RR = 2.5, P = 0.004) than for Xtampza ER. In Treatment Center Programs Combined, past-month abuse prevalence for other ADF ER opioids (odds ratio [OR] = 7.4, P < 0.001) and non-ADF ER opioids (OR = 2.0, P = 0.002) was greater than Xtampza ER; IR oxycodone was not significantly different (OR = 1.2, P = 0.349). In the Drug Diversion Program, rates for IR oxycodone (RR = 3.7, P = 0.003), other ADF ER opioids (RR = 4.2, P = 0.002), and non-ADF ER opioids (RR = 3.4, P = 0.007) were greater than Xtampza ER. Adjustment using morphine equivalents provided similar results, except that IR oxycodone in Treatment Center Programs Combined became higher than Xtampza ER. Nonoral abuse cases involving Xtampza ER were infrequent; Web monitoring data support findings that Xtampza ER is difficult to abuse nonorally.ConclusionXtampza ER abuse, misuse, and diversion and tampering are low relative to other prescription opioid analgesics. Abuse and diversion did not increase over the study period.

Prescription and Prescriber Specialty Characteristics of Initial Opioid Prescriptions Associated with Chronic Use.

This study evaluated the characteristics of opioid prescriptions, including prescriber specialty, given to opioid-naïve patients and their association with chronic use. Cross-sectional analysis of the Ohio prescription drug monitoring program from January 2010 to November 2017. Ohio, USA. Patients who had no opioid prescriptions from 2010 to 2012 and a first-time prescription from January 2013 to November 2016. Chronic use was defined as at least six opioid prescriptions in one year and either one or more years between the first and last prescription or an average of ≤30 days not covered by an opioid during that year. A total of 4,252,809 opioid-naïve patients received their first opioid prescription between 2013 and 2016; 364,947 (8.6%) met the definition for chronic use. Those who developed chronic use were older (51.7 vs 45.6 years) and more likely to be female (53.6% vs 52.8%), and their first prescription had higher pill quantities (44.9 vs 30.2), higher morphine milligram equivalents (MME; 355.3 vs 200.0), and was more likely to be an extended-release formulation (2.9% vs 0.7%, all P < 0.001). When compared with internal medicine, the adjusted odds of chronic use were highest with anesthesiology (odds ratio [OR] = 1.46) and neurology (OR = 1.43) and lowest with ophthalmology (OR = 0.33) and gynecology (OR = 0.37). Eight point six percent of opioid-naïve individuals who received an opioid prescription developed chronic use. This rate varied depending on the specialty of the provider who wrote the prescription. The risk of chronic use increased with higher MME content of the initial prescription and use of extended-release opioids.

Exploring the use of extended release opioids at shortened dosing intervals in people with chronic pain and high risk medication or substance use.

Background Critical attention to rational opioid prescribing has emerged from the opioid epidemic in North America. Individuals with chronic pain are prescribed extended release opioids in an effort to maintain stable drug levels and for more convenient dosing, though evidence to support improvements in pain or function is lacking. It has been observed that extended release opioid products are used at intervals shorter than recommended by product monographs. The need for shortened intervals has been linked with potential inter-patient variability in pharmacokinetics, among other rationale. Implications of shortened dosing intervals for extended release opioids have not been systematically studied. Objective The aim of this study was to characterize the use of extended release opioid formulations at shortened dosing intervals in a population of patients with chronic pain and high risk for opioid-related harms. Setting This study took place in the Interprofessional Pain and Addiction Recovery Clinic, a specialty ambulatory clinic at the Centre for Addiction and Mental Health in Toronto, Canada for adults with chronic pain and a diagnosis or suspicion of substance use disorder. Method This was a retrospective cross-sectional study. Data were collected from records of patients with assessments completed in the years 2012-2017 (n = 210). Main outcome measure Proportion of patients using extended release opioids at shortened intervals. Results Sixty-one percent of individuals using extended release opioids (n = 78) were using them at shortened intervals. This use was associated with a higher daily morphine equivalent dose (533mg vs 236mg, p < 0.01), use of oxycodone extended release products (50% vs. 27%, p < 0.01), a longer duration of opioid therapy (8.9 vs. 6.8years, p = 0.03) and a diagnosis of chronic neuropathic pain (63% vs. 39%, p < 0.01), with no differences in reported pain intensities, compared with use at standard intervals. Conclusion The use of extended release opioids at shortened intervals was associated with increased daily morphine equivalent doses, thus an increased risk of opioid-related mortality. It is unlikely that of those using extended release opioids, the high proportion of use at shortened intervals is the result of inter-patient differences in metabolism alone. Further study is warranted to explore the underlying drivers and implications for people with chronic pain.

High-Risk Opioid Prescribing Trends: Prescription Drug Monitoring Program Data From 2010 to 2018.

Deaths due to opioids have continued to increase in South Carolina, with 816 opioid-involved overdose deaths reported in 2018, a 9% increase from the prior year. The objective of the current study is to examine longitudinal trends (quarter [Q] 1 2010 through Q4 2018) of opioid prescribing volume and high-risk opioid prescribing behaviors in South Carolina using comprehensive dispensing data available in the South Carolina Prescription Drug Monitoring Program (SC PDMP). Retrospective analyses of SC PDMP data were performed using general linear models to assess quarterly time trends and change in rate of each outcome Q1 2010 through Q4 2018. Opioid analgesic prescription fills from SC state residents between Q1 2010 and Q4 2018. High-risk prescribing behaviors included (1) opioid prescribing rate; (2) percentage of patients receiving opioids dispensed 90 or more average morphine milligram equivalents daily; (3) percentage of opioid prescribed days with overlapping opioid and benzodiazepine prescriptions; (4) rate per 100 000 residents of multiple provider episodes; and (5) percentage of patients prescribed extended release opioids who were opioid naive. A total of 33 027 461 opioid prescriptions were filled by SC state residents within the time period of Q1 2010 through Q4 2018. A 41% decrease in the quarterly prescribing rate of opioids occurred from Q1 2010 to Q4 2018. The decrease in overall opioid prescribing was mirrored by significant decreases in all 4 high-risk prescribing behaviors. PDMPs may represent the most complete data regarding the dispensing of opioid prescriptions and as such be valuable tools to inform and monitor the supply of licit opioids. Our results indicate that public health policy, legislative action, and multiple clinical interventions aimed at reducing high rates of opioid prescribing across the health care ecosystem appear to be succeeding in the state of South Carolina.

Perioperative Prescribing Practices of Extended-Release Opioids in Noncancer Surgical Patients, 2015-2018.

Extended-release (ER) opioids are indicated for the management of persistent moderate to severe pain in patients requiring around-the-clock opioid analgesics for an extended period of time. Concerns have been raised regarding safety of ER opioids due to its potential for abuse and dependence. However, little is known about perioperative prescribing practices of ER opioids. This study assessed perioperative prescribing practices of ER opioids in noncancer surgical patients stratified by type of opioid exposure prior to admission and examined predictors of postoperative opioid administration in oral morphine equivalents (OME). This was a retrospective cohort study using the University of California San Francisco Medical Center electronic health record data. This study included 25,396 adult noncancer patients undergoing elective surgery under general anesthesia in the period 2015-2018. The primary study outcome was predictors of postoperative administration of opioids in hospitalized surgical patients. Secondary outcomes included patients discontinued and initiated on ER opioids during their hospital stay. substance use disorder diagnosis and use of opioids, surgery type, and postoperative administration of nonopioid analgesics were associated with postoperative administration of opioids (P < .0001). The estimated adjusted mean (95% confidence interval [CI]) of postoperative administration of OME prior to admission in ER opioid users (170.08 mg; 147.08-196.67) was twice the amount for opioid-naïve patients (81.36 mg; 70.7-93.63; P < .0001). One in 5 prior to admission ER opioid users were weaned off ER opioids while hospitalized without adversely affecting their postoperative pain or hospital length of stay (LOS). Four of 5 patients who used ER opioids prior to admission also received ER opioids after surgery, whereas, 1 in 100 opioid-naïve patients received ER opioids during their hospital stay. We found significant variability in the perioperative prescribing practices of ER opioids in hospitalized noncancer surgical patients by use of opioids prior to admission and surgery type. Pain medicine practitioners and surgeons may play a significant role tackling the surgery-related risk of exposure to ER opioids and decreasing opioid-related complications.

The Effectiveness of Stewardship Interventions to Reduce the Prescribing of Extended-Release Opioids for Acute Pain: A Systematic Review.

To evaluate the effectiveness of stewardship interventions in reducing the prescribing of extended-release opioids for acute pain. Systematic review of randomized controlled trials, pre-post intervention studies, cohort studies and case-control studies. A search was conducted using Medline, Scopus, Cochrane Central Register of Controlled Trials, International Pharmaceutical Abstracts, and PsycINFO from inception to March 24, 2019. Search terms included opioids, interventions, extended-release, and acute pain. Included articles were original research articles outlining the impact of stewardship interventions on reducing the prescribing of extended-release opioids for acute pain. The search resulted in 1,264 articles after the removal of duplicates. Of these, 141 full texts were assessed, with three eligible for inclusion. One additional article was obtained via a manual search. Three studies explored forcing function interventions; two included prior authorization policies, which saw decreases in extended-release/long-acting scripts by 18-36%, while another evaluated order restrictions producing increased adherence to guidelines by 36%. One study explored the impact of education targeting prescribers and patients through a risk mitigation and evaluation strategy, which decreased extended-release/long-acting quarterly script volumes by 4.3%. All studies were performed at system levels. Forcing function interventions decreased extended-release/long-acting prescriptions and increased adherence to guidelines to a greater extent than less restrictive interventions such as education. Forcing function interventions implemented at system levels show promise in decreasing the prescribing of extended-release opioids for acute pain. The current lack of literature warrants future research to increase understanding of the effectiveness of such interventions.

Demographic, Clinical, and Prescribing Characteristics Associated with Future Opioid Use in an Opioid-Naive Population in an Integrated Health System.

Health systems and prescribers need additional tools to reduce the risk of opioid dependence, abuse, and overdose. Identifying opioid-naive individuals who are at risk of opioid dependence could allow for the development of needed interventions. We conducted a retrospective cohort analysis of 23,804 adults in an integrated health system who had received a first opioid prescription between 2010 and 2015. We compared the demographic, clinical, and prescribing characteristics of individuals who later received a third opioid dispense at least 27 days later, indicating long-term opioid use, with those who did not. The strongest predictors of continued opioid use were an initial prescription dosage of 90 morphine milligram equivalence or more; prescription of extended-release opioids, rather than short-release; and being prescribed outside of a hospital setting. Patients with a third prescription were also more likely to be older than 45 years, white, and non-Hispanic and to have physical comorbidities or prior substance abuse or mental health diagnoses. Our findings are largely consistent with prior research but provide new insight into differences in continued opioid use by opioid type, prescribing location, ethnicity, and comorbidities. Together with previous research, our data support a pattern of higher opioid use among older adults but higher rates of diagnosed opioid abuse among younger adults. By identifying population characteristics associated with continued opioid use following a first prescription, our data pave the way for quality improvement interventions that target individuals who are at higher risk of opioid dependence.

Evaluation of Abuse and Route of Administration of Extended-Release Tapentadol Among Treatment-Seeking Individuals, as Captured by the Addiction Severity Index-Multimedia Version (ASI-MV).

BackgroundTapentadol is a molecule incorporating mu opioid receptor agonism and norepinephrine reuptake inhibition to provide analgesia, with the potential for a lower incidence of gastrointestinal side effects than full mu opioid agonists. Postmarketing surveillance of tapentadol as an active pharmaceutical ingredient has consistently revealed low levels of abuse and diversion.ObjectiveThe purpose of the present study was to further characterize the abuse liability of tapentadol extended-release (ER) by evaluating the prevalence of past 30-day tapentadol ER abuse and reported routes of administration as compared with ER opioids with Food and Drug Administration (FDA) abuse-deterrent labeling (“ADF opioids”) and ER opioids without FDA abuse-deterrent labeling (“non-ADF opioids”).MethodsData were collected from January 2014 through December 2017 from 776 centers located in 43 states throughout the United States using the Addiction Severity Index–Multimedia Version (ASI-MV), an instrument that is integral to the National Addictions Vigilance Intervention and Prevention Program (NAVIPPRO, Inflexxion, an IBH Company, Costa Mesa, CA, USA).ResultsTapentadol ER had lower rates of past 30-day abuse than ADF ER and non-ADF ER opioid comparators, both at a population level and when adjusted for drug utilization. Tapentadol ER was primarily abused orally, although it was also abused through alternate routes of administration. Cumulative rates of tapentadol ER abuse by alternative routes of administration were lower than both ADF and non-ADF ER opioid comparators, although large confidence intervals resulting from the small sample size of reported tapentadol ER use limit firm conclusions.ConclusionsIn summary, tapentadol ER was found to have lower rates of both past 30-day abuse and use via alternate routes of administration, specifically snorting and smoking, than ADF and non-ADF ER comparators.

Modeling the potential impact of abuse-deterrent opioids on medical resource utilization

Objectives: To extend a previously published manuscript on a model for estimating potential avoided medical events and cost savings in the US associated with the introduction of extended-release abuse-deterrent opioids and incorporate new methods of evaluating abuse deterrence using human abuse potential studies.Methods: A model was developed to estimate reductions in abuse-related events and annual savings in the US. Model inputs included: opioid abuse prevalence, abuse-deterrent opioid cost and effectiveness at deterring abuse, and opioid abuse-related events and costs. Direct (medical and drug) and indirect (work loss) cost savings (2017 US$) and abuse-related events were estimated assuming the replacement of the entire extended-release opioid market (brand and generic) by brand abuse-deterrent opioids.Results: Replacing the extended-release opioid market with abuse-deterrent opioids is estimated to lower annual abuse-related medical events by ∼13–31% (e.g. 78,000–186,000 emergency department visits) and lower annual medical costs by ∼$640 M–$1,538 M, depending on the abuse-deterrent technology (physical/chemical barrier or agonist/antagonist). Replacement of extended-release oxycodone with extended-release abuse-deterrent oxycodone is associated with the largest amount of cost savings and highest number of avoided medical events, followed by replacing extended-release morphine with an extended-release abuse-deterrent opioid. Replacement of transdermal fentanyl is associated with the smallest amount of cost savings and lowest number of avoided medical events.Conclusion: Agonist/antagonist abuse-deterrent opioid technology is associated with higher annual medical cost savings and more avoided events than physical/chemical barrier technology. Total net savings are dependent upon the abuse-deterrent opioid price relative to non-abuse-deterrent opioids.