5 - Abuse of tapentadol among individuals entering treatment for opioid use disorder

¹Rocky Mountain Poison & Drug Safety – Denver Health and Hospital Authority, Denver, CO, USA. ²University of Colorado School of Medicine, Aurora, CO, USA

Purpose
Tapentadol is centrally acting analgesic thought to have dual mechanisms of action: mu-receptor agonism and inhibition of norepinephrine reuptake. Tapentadol is a schedule II opioid available as an immediate-release (IR; NUCYNTA^®) and extended-release (ER; NUCYNTA ER) formulation. Postmarketing surveillance studies indicate tapentadol abuse and diversion events are rare relative to other opioids. However, studies report abuse is comparable to other schedule II opioids when adjusted for drug utilization. Tapentadol is not a commonly prescribed medication relative to other opioid analgesics. In 2019 there were fewer than 250,000 tapentadol prescriptions filled compared to 19 million oxycodone prescriptions, 26 million hydrocodone prescriptions, and 12 million tramadol prescriptions. The low prescribing volume presents challenges in evaluating the abuse liability of tapentadol using general population data sources. We address this by examining abuse among adults entering treatment for opioid use disorder, a sample at high-risk for abuse of prescription analgesics. This is a descriptive study of tapentadol abuse relative to commonly prescribed opioid analgesics. We compare abuse prevalence and the frequency that each drug group is identified as the primary substance abused in the month prior to enrollment.
Methods
Data collected from 2019 are presented from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS^®) System Treatment Center Programs Combined. In the Treatment Center Programs Combined, respondents entering treatment for opioid use disorders complete a questionnaire asking about prescription medications abused in the past month. Respondents are also asked about their primary opioid drug of abuse, defined as the active pharmaceutical ingredient (API) used the most prior to entering treatment. We compared abuse and primary drug prevalence across the following APIs: total tapentadol, total tramadol, total oxycodone, and total hydrocodone endorsements. We also compared abuse prevalence across formulations: NUCYNTA (IR tapentadol), NUCYNTA ER (ER tapentadol), IR hydrocodone, IR single-entity (SE; not in combination with acetaminophen) oxycodone tablets/capsules, and IR oxycodone combination ingredient tablets/capsules. For abuse cases, unadjusted prevalence and prevalence adjusted for prescriptions dispensed are reported. Prescriptions dispensed estimates were obtained from the IQVIA^® (Danbury, CT) US-Based Longitudinal Patient Data. Prescriptions dispensed adjusted prevalence values are estimated and compared at 1 million prescriptions nationally.
Results
There were 8,001 valid surveys completed; prevalence of tapentadol abuse was 0.17% (n=14), tramadol abuse was 6.95% (n=556), oxycodone abuse was 25.60% (n=2,048), and hydrocodone abuse was 18.40% (n=1,472). The prevalence of primary drug of abuse endorsements was 0.15% (n=12) for tapentadol, 2.56% (n=205) for tramadol, 18.87% (n=1,510) for oxycodone, and 11.34% (n=907) for hydrocodone.
The prescription adjusted prevalence for past month abuse was 0.80% (95% CI: 0.47% to 1.35%) for tapentadol. This was greater than tramadol (0.57%, 95% CI: 0.52% to 0.61%), similar to hydrocodone (0.72%, 95% CI: 0.68% to 0.75%), and less than oxycodone (1.36%, 95% CI: 1.30% to 1.41%). Among tapentadol abuse cases, 14.28% (n=2) identified tapentadol as their primary drug of abuse. Among tramadol abuse cases, 22.30% (n=124) identified tramadol was a primary drug of abuse, 47.27% (n=968) of oxycodone abuse cases identified oxycodone as a primary drug, and 37.29% (n=549) of hydrocodone users identified hydrocodone as a primary drug of abuse.
By formulation, NUCYNTA abuse (n=2) and NUCYNTA ER abuse (n=4) was indicated on less than 0.1% of surveys. IR hydrocodone abuse was indicated on 10.17% (n=814) of surveys, IR SE oxycodone abuse on 5.52% (n=442) of surveys, and combination ingredient IR oxycodone abuse on 914 (11.42%) of surveys. Abuse prevalence adjusted for utilization was lowest for NUCYNTA (0.19%, 95% CI: 0.05% to 0.77%), followed by IR hydrocodone (0.40%, 95% CI: 0.38 to 0.43%), NUCYNTA ER (0.56%, 95% CI: 0.21% to 1.50%), IR SE oxycodone (0.75%, 95% CI: 0.68% to 0.82%), and highest for IR combination ingredient oxycodone (1.10%, 95% CI: 1.04% to 1.17%).
Conclusions
The abuse of tapentadol is infrequent relative to other opioids among individuals entering treatment for opioid use disorders. Relative to prescribing however, tapentadol abuse is greater than tramadol, similar to hydrocodone, and lower than oxycodone. Tapentadol is less likely to be endorsed as a primary drug of abuse than tramadol, oxycodone, and hydrocodone. Among tapentadol abuse cases, the percentage of cases reporting tapentadol as a primary drug is low relative to primary drug prevalence among tramadol, oxycodone, and hydrocodone abuse cases. When examining cases involving specific products, abuse of NUCYNTA was less frequent than all comparator drug groups and abuse of NUCYNTA ER was less frequent than all drug groups except IR hydrocodone after adjusting for prescriptions dispensed. This study has limitations. Abuse estimates are based on self-report and no adjustments were made for differences between active pharmaceutical ingredients in missing data. Noting these limitations, this study provides insight into tapentadol abuse among individuals entering treatment for opioid use disorder. Specifically, abuse relative to utilization may be similar to frequently prescribed comparators although tapentadol is less likely to be identified as a preferred drug. Given low prescribing volume, continued examination into the motivations for abuse of tapentadol products is needed.