Abuse and Diversion of Immediate Release Opioid Analgesics as Compared to Extended Release Formulations in the United States

Abstract

BackgroundTherapeutic use and abuse of prescription opioids in the United States increased substantially between 1990 and 2010. The Centers for Disease Control estimated deaths related to pharmaceutical opioids reached nearly 19,000 in 2014. Of prescription opioids sold, 10% are extended release (ER) and 90% immediate release (IR). However, most regulations and interventions have focused on decreasing ER abuse. Our objective was to compare rates of abuse and diversion of ER and IR opioid analgesics over time using multiple surveillance programs.MethodsRates of abuse and diversion of ER and IR opioid formulations were compared using data from four surveillance programs in the Researched Abuse, Diversion and Addiction Related Surveillance (RADARS®) System. Data were evaluated from 2009 through 2015, and Poisson regression used to compare IR and ER opioid cases over time.ResultsFrom 2009 to 2015, IR opioids were prescribed at a rate 12 to 16 times higher than ER. In the Poison Center Program, population-adjusted rates of Intentional Abuse for IR were 4.6 fold higher than ER opioids (p<0.001). In the Drug Diversion Program, population-adjusted rates of diversion were 6.1 fold higher for IR than ER opioids (p<0.001). In the Opioid Treatment Program, population-adjusted rates of endorsements for abuse were 1.6 fold higher for IR opioids than ER (p = 0.002). In the Survey of Key Informants' Patients Program, population-adjusted rates of endorsements for abuse were 1.5 fold higher for IR opioids than ER (p<0.001).ConclusionsBetween 2009 and 2015, IR opioids were prescribed at a much higher rate than ER opioids. Results from four surveillance programs show population-adjusted rates of prescription opioid abuse were markedly higher for IR than ER medications. For the greatest public health benefit, future interventions to decrease prescription opioid abuse should focus on both IR and ER formulations.

Understanding multi‐pill ingestion of prescription opioids: Prevalence, characteristics, and motivation

“…While further analysis is needed to understand how much of the overdose burden involves multi‐pill use, several implications stand out in terms of prevention: First, development of affordable and effective pill dispensers may be useful for high‐risk patients and have been shown to be effective for buprenorphine adherence; second, due to the large quantities of pills ingested, encouraging greater utilization of prescription monitoring programs or prescribing guidelines could serve to deter access; third, multi‐pill use of intact tablets will not be prevented through abuse‐deterrent formulations meant to reduce/inhibit non‐oral use. Novel “abuse‐deterrent formulations” should be a higher priority in terms of (1) effectively deterring the effects or release of drug from ingesting multiple opioid tablets and (2) immediate‐release opioids, which were the most commonly ingested in our sample and which are prescribed at rates that vastly outnumber those for extended‐release opioids …”

Changes in drug use patterns reported on the web after the introduction of ADF OxyContin: findings from the Researched Abuse, Diversion, and Addiction‐Related Surveillance (RADARS) System Web Monitoring Program

“…Probabilities that individuals might use alternate routes of administration with IR formulations of these molecules was estimated to be around 0.20 or greater for oxycodone (intranasal = 0.26), hydromorphone (intravenous = 0.55, intranasal = 0.21), morphine (intravenous = 0.56, intranasal = 0.17), or oxymorphone (intranasal = 0.54). It is possible to infer that reformulation of only select ER opioids may not be enough of an effort to counter prescription opioid abuse . Although some abuse has switched to other ER compounds, many posts conveyed preference for and shifting to IR products.…”

“…Switching to heroin was a concern upon the introduction of the ADFs because of the possible public health implications . Multiple sources have documented various aspects of this pattern and reported increased heroin use . Other studies report that increased heroin use has taken place over the last 2 decades, has occurred among users of multiple drugs, not just prescription opioids, and may be in part related to the accessibility, increased purity, and decreased cost of heroin .…”

“…High levels of immediate‐release (IR) opioid abuse have been reported after reformulation in some, but not all, data sets. When individuals seeking treatment for opioid abuse were asked whether they preferred ER or IR opioids to get high, a majority (66%) reported an IR opioid preference …”

Individual short‐acting opioids and the risk of opioid‐related adverse events in adolescents

“…Oxycodone prescribing has been controversial because it is one of the most frequently abused prescription opioids . Although efforts to reduce abuse have focused on the extended‐release preparations, there is evidence of considerable abuse of immediate‐release formulations …”