Abuse of tapentadol compared to other atypical opioids among individuals entering treatment for opioid use disorders.

OBJECTIVE: Tapentadol is an atypical opioid analgesic thought to have dual mechanisms of action: µ-receptor agonism and inhibition of norepinephrine reuptake. Unlike other atypical opioids, tapentadol is a schedule II-controlled substance. We compared the prevalence of abuse (use to get high) of tapentadol to other atypical opioids used to treat pain (buprenor-phine and tramadol). DESIGN: An observational, serial cross-sectional study. SETTING: Individuals enrolling in treatment programs for opioid use disorder in 2019. Each completed a self-administered, paper questionnaire assessing prescription drug abuse and illegal drug use within 1 week of enrollment. MAIN OUTCOME MEASURES: Indication of past month abuse of tapentadol or comparator drugs on a self-administered ques-tionnaire. RESULTS: There were 6,987 respondents. Unadjusted and utilization-adjusted logistic regression models were used to compare odds of endorsement of tapentadol to tramadol and buprenorphine products indicated for the management of pain. Unadjusted abuse prevalence was 0.20 percent for total tapentadol (0.03 percent for NUCYNTA® and 0.06 percent for NUCYNTA ER). Relative to total tapentadol, the odds of abuse of buprenorphine for pain was 2.9 times greater (95 percent CI: 1.6 to 5.3, p < 0.001), and for tramadol, 43.1 times greater (95 percent CI: 25.3 to 73.3, p < 0.001). Adjusting for prescriptions dispensed, differences in odds of abuse were not statistically significant (odds ratio (OR) = 1.6, 95 per-cent CI: 0.9 to 3.0, p = 0.108 for buprenorphine for pain and OR = 0.7, 95 percent CI: 0.4 to 1.2, p = 0.209 for tramadol). CONCLUSIONS: Tapentadol use to get high is less frequent than other atypical opioids. Findings suggest tapentadol is rarely the primary drug abused by an individual.

Initiation Patterns and Transitions Among Adults Using Stimulant Drugs: Latent Transition Analysis.

BACKGROUND: The fourth wave of the drug overdose epidemic in the United States includes increasing rates of stimulant-involved overdose. Recent studies of transitions leading to stimulant misuse have shown complex patterns that are not universally applicable because they have isolated individual populations or individual behaviors. A comprehensive analysis of transitions between behaviors and the associations with present-day problematic drug use has not been conducted. OBJECTIVE: This study aims to determine whether adults from the general population who use stimulants initiate use through a heterogeneous combination of behaviors and quantify the association between these typologies with present-day problematic drug use. METHODS: Individuals who have reported use of any stimulant in their lifetime were recruited from the 2021 Survey of Nonmedical Use of Prescription Drugs Program, a nationally representative web-based survey on drug use, to participate in a rapid follow-up survey about their past stimulant use. Individuals were asked which stimulants they used, the reasons for use, the routes of administration, and the sources of the stimulant. For each stimulant-related behavior, they were asked at what age, between 6 and 30 years, they initiated each behavior in a 6-year time window. A latent transition analysis was used to characterize heterogeneity in initiation typologies. Mutually exclusive pathways of initiation were identified manually by the researchers. The association of these pathways with present-day problematic drug use was calculated using logistic regression adjusted by the current age of the respondent. RESULTS: From a total of 1329 participants, 740 (55.7%) reported lifetime prescription stimulant use and 1077 (81%) reported lifetime illicit stimulant use. Three typologies were identified. The first typology was characterized by illicit stimulant initiation to get high, usually via oral or snorting routes and acquisition from friends or family or a dealer (illicit experimentation). The second typology was characterized by low, but approximately equal probabilities of initiating 1-2 new behaviors in a time window, but no singular set of behaviors characterized the typology (conservative initiation). The third was characterized by a high probability of initiating many diverse combinations of behaviors (nondiscriminatory experimentation). The choice of drug initiated was not a strong differentiator. Categorization of pathways showed those who were only in an illicit experimentation status (reference) had the lowest odds of having severe present-day problematic drug use. Odds were higher for a conservative initiation-only status (odds ratio [OR] 1.84, 95% CI 1.14-2.94), which is higher still for those moving from illicit experimentation to conservative initiation (OR 3.50, 95% CI 2.13-5.74), and highest for a nondiscriminatory experimentation status (OR 5.45, 95% CI 3.39-8.77). CONCLUSIONS: Initiation of stimulant-related use behaviors occurred across many time windows, indicating that multiple intervention opportunities are presented. Screening should be continued throughout adulthood to address unhealthy drug use before developing into full substance use disorders.

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 centers between 2016 and 2021 inclusive that 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 oxycodone and 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.

Differing Behaviors Around Adult Nonmedical Use of Prescription Stimulants and Opioids: Latent Class Analysis.

BACKGROUND: The availability of central nervous system stimulants has risen in recent years, along with increased dispensing of stimulants for treatment of, for example, parent-reported attention-deficit/hyperactivity disorder in children and new diagnoses during adulthood. Typologies of drug use, as has been done with opioids, fail to include a sufficient range of behavioral factors to contextualize person-centric circumstances surrounding drug use. Understanding these patterns across drug classes would bring public health and regulatory practices toward precision public health. OBJECTIVE: The objective of this study was to quantitatively delineate the unique behavioral profiles of adults who currently nonmedically use stimulants and opioids using a latent class analysis and to contrast the differences in findings by class. We further evaluated whether the subgroups identified were associated with an increased Drug Abuse Screening Test-10 (DAST-10) score, which is an indicator of average problematic drug use. METHODS: This study used a national cross-sectional web-based survey, using 3 survey launches from 2019 to 2020 (before the COVID-19 pandemic). Data from adults who reported nonmedical use of prescription stimulants (n=2083) or prescription opioids (n=6127) in the last 12 months were analyzed. A weighted latent class analysis was used to identify the patterns of use. Drug types, motivations, and behaviors were factors in the model, which characterized unique classes of behavior. RESULTS: Five stimulant nonmedical use classes were identified: amphetamine self-medication, network-sourced stimulant for alertness, nonamphetamine performance use, recreational use, and nondiscriminatory behaviors. The drug used nonmedically, acquisition through a friend or family member, and use to get high were strong differentiators among the stimulant classes. The latter 4 classes had significantly higher DAST-10 scores than amphetamine self-medication (P<.001). In addition, 4 opioid nonmedical use classes were identified: moderate pain with low mental health burden, high pain with higher mental health burden, risky behaviors with diverse motivations, and nondiscriminatory behaviors. There was a progressive and significant increase in DAST-10 scores across classes (P<.001). The potency of the opioid, pain history, the routes of administration, and psychoactive effect behaviors were strong differentiators among the opioid classes. CONCLUSIONS: A more precise understanding of how behaviors tend to co-occur would improve efficacy and efficiency in developing interventions and supporting the overall health of those who use drugs, and it would improve communication with, and connection to, those at risk for severe drug outcomes.

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

BACKGROUND AND OBJECTIVE: 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. METHODS: 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. RESULTS: 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% CI 0.11, 0.50], p = 0.0002) and ER oxymorphone (OR = 0.30 [95% CI 0.14, 0.67], p = 0.0038). Oxycodone myristate was not significantly different from other ER oxycodone opioids (OR = 0.5 [95% CI 0.24, 1.03], p = 0.0612). These findings did not change when the estimates were adjusted for age and sex. CONCLUSIONS: 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.

Changes in the Street Prices of Prescription Opioids During the COVID-19 Pandemic.

OBJECTIVE: This study analyzed changes in prescription opioid street prices during the COVID-19 pandemic. METHODS: Crowdsourced prescription opioid street prices were obtained from the Researched Abuse, Diversion and Addiction-Related Surveillance System StreetRx Program. Percentage changes in street price per milligram of different opioids between April and December 2020 compared with the same months in 2019 were calculated by using linear regression. RESULTS: Street prices of high-potency drugs hydromorphone and oxycodone increased 23% and 12% per milligram, respectively. Prices of low-potency drugs hydrocodone and morphine increased 9% and 12% per milligram, respectively. Changes in prices of medications for opioid use disorder were not statistically significant. CONCLUSIONS: Decreased access to opioid analgesics during the pandemic combined with contributors to opioid demand may have led to increases in street prices of prescription opioids. Measures taken to increase access to medications for opioid use disorder were not associated with changes in those drugs' street prices.

Clustering patterns in polysubstance mortality in the United States in 2017: a multiple correspondence analysis of death certificate data.

PURPOSE: The main goal of this analysis was to identify mortality patterns apparent when many drug classes are analyzed together. METHODS: The Drug Involved Mortality database is a registry of drug terms mentioned on death certificates of all drug-related deaths in the United States. Means of total number of drugs involved and percentages of specific drug combinations were calculated. Dimensionality reduction using multiple correspondence analysis and hierarchical clustering identified clusters of drugs listed on death certificates. RESULTS: An average of 2.4 specific drugs were listed on death certificates in 2017. For 9 of the top 10 drugs involved, over 80% of deaths involved at least one other drug. As expected, opioid drugs and psychostimulants clustered together, but other psychoactive substances (non-opioid analgesics, sedatives, antidepressants, antipsychotics) clustered together into multi-class groups. Other drugs (e.g., acetaminophen, oxymorphone) were frequently involved in polysubstance death, but did not cluster with any other specific drug. Deaths involving illicit drugs listed fewer drugs than deaths involving prescription drugs. CONCLUSIONS: While individual drug substances might contribute to many deaths (e.g., fentanyl), polysubstance mortality is more common than single substance mortality. Multidimensional analyses integrating all drugs involved are useful to identify uncommon patterns of overdose and changing trends.

Evaluation of Cannabis Use Among US Adults During the COVID-19 Pandemic Within Different Legal Frameworks.

This cross-sectional study analyzes the prevalence of cannabis use by US adults during the COVID-19 pandemic within different legal frameworks and evaluates differences in associated behaviors.

Trends in characteristics of fentanyl-related poisonings in the United States, 2015-2021.

Background: Fentanyl-related deaths continue to increase in the United States; however, most national studies focus on fatal overdose. More research, including data on nonfatal overdose, is needed.Objective: We examined trends in characteristics of fatal and nonfatal fentanyl-related poisonings ("exposures") in the US.Methods: National Poison Control data were examined to estimate trends in characteristics of reported exposures between 2015 and 2021 (N = 15,391; 38.7% female). We also delineated correlates of experiencing a major adverse effect or death.Results: The proportion of exposures increased among all age groups between ages 13 and 39 (ps < .05) with the largest increase among those age 13-19 (a 127.8% increase). With respect to reasons for use, the proportion of cases involving fentanyl "abuse" increased by 63.8% (p < .001). The proportion involving fentanyl inhalation increased 427.6% from 5.7% to 29.9% and injection increased from 6.7% to 9.6%, a 42.3% increase (ps < .01). The proportion also increased for co-use of methamphetamine (by 669.0%), cocaine (by 374.0%), and heroin (by 159.5%). The proportion of major adverse effects increased from 15.5% to 39.6% (p < .001). In the multivariable model, "abuse", suspected suicide attempts, and use via inhalation were risk factors for experiencing a major effect or death, and misuse, ingestion, dermal use, and co-use of methamphetamine were associated with lower risk.Conclusion: Poison Control data suggest that characteristics of individuals exposed to fentanyl continue to shift, with use via inhalation increasing and medical outcomes of nonfatal poisonings becoming more severe. These results complement mortality data and inform prevention and harm reduction efforts.

Changes in Hydrocodone Misuse Exposures Reported to U.S. Poison Centers Following Rescheduling in 2014.

BACKGROUND: In 2014, the Drug Enforcement Administration rescheduled hydrocodone combination products to Schedule II to reduce nonmedical use and diversion. METHODS: The impact of rescheduling was assessed using quarterly data from 2011 through 2019 from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS®) System Poison Center Program and IQVIATM Longitudinal Prescription Data. Trends and immediate changes in prescriptions dispensed and misuse exposures before and after rescheduling involving hydrocodone, oxycodone, and other Schedule II opioid analgesics were calculated using segmented regression. RESULTS: Hydrocodone prescriptions were stable pre-rescheduling, decreased by 2.7% (95% CI: -3.6%, -1.8%, p < 0.0001) per quarter post-rescheduling. Misuse exposures involving hydrocodone were decreasing by 3.2% (95% CI: -3.9%, -2.4%, p < 0.0001) per quarter pre-rescheduling and decreased by 4.9% (95% CI: -5.5%, -4.2%, p < 0.0001) post-rescheduling. Immediate decreases in hydrocodone prescriptions and misuse exposure rates in 2014Q4 compared to 2014Q3 were significant and different from oxycodone or other Schedule II opioids. Schedule II opioid analgesics prescriptions in aggregate were stable prior to rescheduling, decreased by 10.8% (95%CI: -14.0%, -7.6%, p < 0.0001) immediately after the rescheduling, and decreased by 2.3% per quarter (95% CI: -3.1%, -1.5%, p < 0.0001) subsequently. Misuse exposures involving these opioids were decreasing by 3.3% (95% CI: -4.1%, -2.5%, p < 0.0001) prior to rescheduling then by 2.8%, (95% CI: -3.4%, -2.2%, p < 0.0001) after rescheduling. The immediate change in misuse was not significant. CONCLUSIONS: Rescheduling corresponded with changes in hydrocodone prescribing and misuse not offset by increases in other Schedule II opioid analgesics. Misuse exposures for hydrocodone and comparators were decreasing prior to rescheduling with little change post-intervention.

The association between the availability of over the counter codeine and the prevalence of non-medical use.

PURPOSE: To investigate the prevalence of non-medical use (NMU) of codeine in Germany, Italy, Spain and the UK and whether availability of OTC codeine has any association with NMU of the drug. METHODS: Data collected in the online Survey of Non-Medical Use of Prescription Drugs, in surveys launched in the second half of 2018 from (Germany (n = 14,969), Italy, (n = 9974), Spain (n = 9912) and the UK (n = 9819) were analysed. For each survey, the estimated prevalence and 95% confidence interval (CI) of respondents reporting NMU of prescription and/or OTC codeine within the last 12 months were calculated and compared. RESULTS: The prevalence of last 12-month NMU in Spain was 12.6% (95% CI 11.7-13.6) for prescription codeine, 6.3% (5.6-7.0) for OTC codeine and 16.1% (15.1-17.3) for any codeine (prescription and/or OTC). The prevalence of last 12-month NMU in the UK was 5.4% (4.9-5.8) for prescription codeine, 4.5% (4.1-5.0) for OTC codeine and 8.3% (7.8-8.9) for any codeine (prescription and/or OTC). The prevalence of last 12-month NMU for prescription codeine was 2.1% (1.9-2.4) in Germany and 1.9% (1.7-2.2) in Italy. CONCLUSION: The prevalence of last 12-month NMU of any codeine product is approximately eight times greater in Spain and four times greater in the UK compared to Germany and Italy where the drug is only available by prescription. While other factors may contribute, these findings suggest that availability of codeine OTC is associated with greater NMU.

Web-Based Discussion and Illicit Street Sales of Tapentadol and Oxycodone in Australia: Epidemiological Surveillance Study.

BACKGROUND: Opioid use disorder and its consequences are a persistent public health concern for Australians. Web activity has been used to understand the perception of drug safety and diversion of drugs in contexts outside of Australia. The anonymity of the internet offers several advantages for surveilling and inquiring about specific covert behaviors, such as diversion or discussion of sensitive subjects where traditional surveillance approaches might be limited. OBJECTIVE: This study aims to characterize the content of web posts and compare reports of illicit sales of tapentadol and oxycodone from sources originating in Australia. First, post content is evaluated to determine whether internet discussion encourages or discourages proper therapeutic use of the drugs. Second, we hypothesize that tapentadol would have lower street price and fewer illicit sales than oxycodone. METHODS: Web posts originating in Australia between 2017 and 2019 were collected using the Researched Abuse, Diversion, and Addiction-Related Surveillance System Web Monitoring Program. Using a manual coding process, unstructured post content from social media, blogs, and forums was categorized into topics of discussion related to the harms and behaviors that could lead to harm. Illicit sales data in a structured format were collected through a crowdsourcing website between 2016 and 2019 using the Researched Abuse, Diversion, and Addiction-Related Surveillance System StreetRx Program. In total, 2 multivariable regression models assessed the differences in illicit price and number of sales. RESULTS: A total of 4.7% (28/600) of tapentadol posts discussed an adverse event, whereas 10.27% (95% CI 9.32-11.21) of oxycodone posts discussed this topic. A total of 10% (60/600) of tapentadol posts discussed unsafe use or side effects, whereas 20.17% (95% CI 18.92-21.41) of oxycodone posts discussed unsafe use or side effects. There were 31 illicit sales reports for tapentadol (geometric mean price per milligram: Aus $0.12 [US $0.09]) and 756 illicit sales reports for oxycodone (Aus $1.28 [US $0.91]). Models detected no differences in the street price or number of sales between the drugs when covariates were included, although the potency of the pill significantly predicted the street price (P<.001) and availability predicted the number of sales (P=.03). CONCLUSIONS: Australians searching the web for opinions could judge tapentadol as safer than oxycodone because of the web post content. The illicit sales market for tapentadol was smaller than that of oxycodone, and drug potency and licit availability are likely important factors influencing the illicit market.

Drug product dispensing and estimates of use in a general population survey as a signal detection problem.

PURPOSE: Understanding potential bias due to rarity of the outcome is important when monitoring newly approved drugs and drugs with low availability to the general public. Although there is an increasing use of online surveys to investigate health outcomes, the limits of inference due to drug availability have not been studied. The goal of this study was to quantify the relationship between dispensing of prescription drugs and estimates of use in an online general population survey. METHODS: An online repeated, cross-sectional survey from 2018 to 2020 was used to estimate the number of adults in the United States who used prescription drugs in the general population and compared to estimated number of prescriptions dispensed over an equivalent time period. Joinpoint regression was used to quantify thresholds. A sample of respondents was retested to estimate reliability statistics. RESULTS: A model with a single threshold was the best fit, with the estimated threshold of 565 000 (95% CI: 9500-11 600 000) prescriptions dispensed per year. Above the threshold, there was a significant association between dispensing and estimates (p < 0.001); below the threshold, the relationship was not significant (p = 0.912). Above the threshold, responses were more reliable than random chance, and reliability steadily increased with increased dispensing. CONCLUSIONS: These results suggest the threshold demarcates two distinct pharmacoepidemiological paradigms when investigating drug use in general population surveys. Dispensing can be used as a guide to determine the epidemiological paradigm that is best suited.

Measuring prescription opioid misuse and its consequences.

AIMS: Prescription drug misuse in the USA increased during the 1990s to 2010. The epidemic stimulated the need new analytical strategies and techniques to understand the medications involved, user characteristics and other factors needed to address the epidemic. METHODS: A strategy of mosaic surveillance has evolved. Using real world evidence, the goal is to paint a more complete profile of a drug's real world misuse using triangulation-integrating results from multiple sources, where each approach has unrelated sources of bias. RESULTS: Research findings have been remarkably consistent across multiple data sources. The most commonly misused opioid medications: hydrocodone = oxycodone > methadone = buprenorphine = tramadol = fentanyl (prescription form) > morphine > hydromorphone = oxymorphone > tapentadol. This rank order is similar to the number of prescriptions dispensed for each product in the USA. In the USA, prescription opioid misuse started to decrease about 2011. Typically, multiple drugs are misused together, particularly in lethal cases. Immediate release formulations are more commonly misused than extended release formulations. The introduction of tamper resistant formulations to resist crushing were followed by a decrease in misuse of those products. CONCLUSIONS: The rapid expansion of opioid prescribing was accompanied by increasing misuse and mortality. Interventions such as prescription drug monitoring programmes, increased law enforcement and abuse deterrent formulations have been followed by decreases in misuse of most opioid analgesics.

Prevalence and description of kratom (Mitragyna speciosa) use in the United States: a cross-sectional study.

BACKGROUND AND AIMS: Mitragyna speciosa ('kratom') contains mu opioid partial agonists. It is widely available, and occasionally used as a home remedy for opioid use disorder. The Drug Enforcement Agency considers kratom a drug of concern; however, prevalence of use and role in drug misuse are unknown. This study aimed to characterize kratom use in the United States. DESIGN: Cross-sectional Survey of Non-Medical Use of Prescription Drugs (NMURx) Program, 2018 third quarter and 2019 first quarter. SETTING: A validated non-probability online survey in the United States. PARTICIPANTS: A total of 59 714 respondents aged 18 years or older, weighted to represent the adult US population (n = 252 063 800). MEASUREMENTS: In addition to prevalence of past-year kratom and other drug use, behavior proportions were estimated. The Drug Abuse Screening Test (DAST-10) estimated consequences of drug abuse. FINDINGS: The estimated prevalence of past-year kratom use in the adult US population was 0.8% [95% confidence interval (CI) = 0.7-0.9], representing 2 031 803 adults. Life-time prevalence was 1.3% (95% CI = 1.2-1.4), representing 3 353 624 adults. Kratom users were younger (mean 35 years, P < 0.001), with higher proportions of males (61.0 versus 48.6%, P < 0.001), students (14.1 versus 7.5%, P < 0.001) and health-care professionals (9.7 versus 4.5%, P < 0.001) and fewer bachelor's/advanced degree graduates (33.4 versus 42.6%, P < 0.001) compared with non-users. Results were inconclusive on whether there was a difference in kratom use by race, household income or employment status. Among those with past-year kratom use, 36.7% (95% CI = 32.1-41.3) non-medically used prescription opioids, 21.7% (95% CI = 18.0-25.5) used illicit opioids, 54.4% (95% CI = 49.5-59.3) used another illicit drug and 67.1% (95% CI = 62.5-71.8) used cannabis. The DAST-10 profile was more often substantial/severe in kratom users (21 versus 1%, P < 0.001) compared with non-users. CONCLUSIONS: Estimated United States past-year prevalence of kratom use is 0.8%, and kratom users tend to have more serious substance abuse profiles than non-users or users of cannabis, alcohol or cigarettes. To our knowledge, this is the first description of kratom use at the national level.

Tramadol non-medical use in Four European countries: A comparative analysis.

BACKGROUND: Understanding prescription medication misuse is challenging due to lack of consistent measures of misuse behaviors and prevalence between countries. Tramadol is an atypical opioid with a dual mechanism, and has low drug liking compared to conventional opioids. We evaluate tramadol misuse compared to conventional opioids utilizing a harmonized validated national survey across four countries: Germany, Italy, Spain, and the United Kingdom (UK). METHODS: Data from the Survey of Non-Medical Use of Prescription Drugs (NMURx) Program online cross-sectional general population national surveys are analyzed from 2018 from four countries, with 45,000 total responses. Misuse and abuse of tramadol, codeine, morphine, and oxycodone are compared, and national prevalence estimates calculated via calibration weighting. Rates are calculated per population and per drug availability. Supplemental data are included from patients entering treatment centres and poison centre exposures. RESULTS: In 2018, distribution, misuse, and abuse of four prescription opioids show similar patterns across four countries. In all countries, codeine is misused by the largest number of adults (estimated 861,181 in Italy to 4,676,680 in Spain in past 12 months). When adjusted for availability, tramadol is misused uncommonly with lowest or second lowest rates in all countries. Most abuse occurs by the oral route for all opioids, including tramadol with only 7.27 (Germany) to 54.92 (UK) cases per 100,000 units sold. CONCLUSIONS: In four countries, tramadol misuse and abuse are infrequent both in absolute number of cases and in comparison to conventional opioids. Even with availability of intravenous tramadol formulations, misuse by injection is rare.

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

OBJECTIVE: To evaluate abuse, misuse, and diversion of Xtampza ER, an extended-release (ER) abuse-deterrent formulation (ADF) of oxycodone. METHODS: Abuse, 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. RESULTS: Xtampza 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. CONCLUSION: Xtampza 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.