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

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 < 0.001). Mortality rates for benzodiazepines and hydrocodone also decreased and were not statistically different. Significant heterogeneity in mortality rates of individual opioids was observed between the three states. When adjusted for prescription volume, the ER/LA opioid analgesic mortality rate decreased in all three states, but was significant only for Washington (P < 0.001). CONCLUSIONS: The 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.

Scoring the best deal: Quantity discounts and street price variation of diverted oxycodone and oxymorphone.

PURPOSE: Diverted prescription opioids are significant contributors to drug overdose mortality. Street price has been suggested as an economic metric of the diverted prescription opioid black market. This study examined variables that may influence the street price of diverted oxycodone and oxymorphone. METHODS: A cross-sectional study was conducted utilizing data from the previously validated, crowdsourcing website StreetRx. Street price reports of selected oxycodone and oxymorphone products, between August 22, 2014 and June 30, 2016, were considered for analysis. Geometric means and 95% confidence intervals were calculated comparing prices per milligram of drug in US dollars. Univariate and multivariable regressions were used to examine the influence of dosage strength, drug formulation, and bulk purchasing on street price. RESULTS: A total of 5611 oxycodone and 1420 oxymorphone reports were analyzed. Across various dosages and formulations, geometric mean prices per milligram ranged between $0.12 and $1.07 for oxycodone and $0.73 and $2.90 for oxymorphone. For a 2-fold increase in dosage strength, there is a 24.0% (95% CI: -28.1%, -19.6%, P < 0.001) and a 22.5% (95% CI: -24.2%, -20.8%, P < 0.001) decrease on average in price per milligram for oxycodone and oxymorphone, respectively. Lower potency, high dosage strength, crush-resistant opioids, and those purchased in bulk were significantly cheaper. CONCLUSION: Street prices for diverted oxycodone and oxymorphone are influenced by multiple factors including potency, dosage, formulation, and bulk purchasing. Buyers who purchase large quantities of low potency, large dosage, crush-resistant formulation prescription opioids can expect to achieve the lowest price.

Shifting Trends in Diagnosis of Asthma, Bronchiolitis, and Viral Pneumonia in Young Children.

Over the last decade, there have been widespread efforts to reduce non-evidence-based therapies for viral bronchiolitis. We question whether this change in practice has inadvertently impacted the diagnosis and management of other pediatric lower-respiratory-tract illnesses. We used the Pediatric Health Information System (PHIS) and logistic regression to describe trends in relative diagnosis frequency of bronchiolitis, viral pneumonia, and reactive airway disease (RAD)/asthma as well as systemic corticosteroid use among children of the age range 1 to 4 years over a 10-year period. Among 169,207 children, the relative frequency of asthma/RAD diagnoses declined over a 10-year period, while bronchiolitis and viral pneumonia diagnoses increased among children of the age range 1 to 3 years and 2 to 4 years, respectively. Frequency of systemic corticosteroid use declined. We question whether the observed shift in diagnosis from asthma/RAD to bronchiolitis or viral pneumonia is reflective of true disease pathophysiology or if it represents an unintended consequence of campaigns surrounding bronchiolitis.

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.

Unit-Dose Packaging and Unintentional Buprenorphine-Naloxone Exposures.

BACKGROUND AND OBJECTIVES: Buprenorphine accounts for the most opioid-related pediatric hospital admissions when compared with other opioid analgesics. Since 2010, several manufacturers began distributing their buprenorphine products with unit-dose packaging (UDP). Our main objective in this study is to evaluate the impact of UDP on unintentional pediatric buprenorphine-naloxone poison center exposures. METHODS: This is an observational surveillance study in which the Researched Abuse, Diversion, and Addiction-Related Surveillance System Poison Center Program is used. The main outcome was cases of unintentional ingestions involving children <6 years old and buprenorphine-naloxone (combination) products. The study was split into 3 periods: pre-UDP (first quarter 2008 through fourth quarter 2010), transition to UDP (first quarter 2011 through fourth quarter 2012), and post-UDP (first quarter 2013 through fourth quarter 2016). RESULTS: Overall, there were 6217 exposures to combination products. In the pre-UDP period, there were 20.57 pediatric unintentional exposures per 100 000 prescriptions dispensed; in the transition to UDP period, there were 8.77 pediatric unintentional exposures per 100 000 prescriptions dispensed; and in the post-UDP period, there were 4.36 pediatric unintentional exposures per 100 000 prescriptions dispensed. This represents a 78.8% (95% confidence interval: 76.1%-81.3%; P < .001) relative decrease from the pre-UDP period. CONCLUSIONS: The shift from non-UDP to UDP in over 80% of buprenorphine-naloxone products was associated with a significant decrease in unintentional pediatric exposures reported to poison centers. Packaging controls should be a mainstay in the approach to the prevention of unintentional buprenorphine pediatric exposures as well as exposures to other prescription opioids.