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

Abstract

Purpose Hydrocodone, codeine, oxycodone, and tramadol are frequently prescribed to adolescents for moderate pain related to minor trauma or dental, surgical, or medical procedures. Pharmacokinetic and pharmacodynamic differences between these opioids could affect their relative safety. We aimed to compare occurrence of opioid‐related adverse events in adolescents without cancer or other severe conditions taking hydrocodone, codeine, oxycodone, and tramadol. Methods Retrospective cohort study of 201 940 Tennessee Medicaid enrollees 12 to 17 years of age without cancer, other severe conditions, or evidence of substance abuse with 529 731 filled prescriptions for study opioids. Adverse events were defined as an emergency department visit, hospital admission, or death related to opioid use, confirmed by medical record review. Serious events had opioid‐related escalation of care, hospitalization, or death. Propensity‐score adjusted hazard ratios (HRs) were calculated with hydrocodone as the reference category. Results The incidence of opioid‐related adverse events per 10 000 person‐years of opioid exposure was 97.5 for hydrocodone (127 events/13 026 person‐years), 91.2 for codeine (58/6,359), 229.7 for oxycodone (43/1,872), and 317.7 for tramadol (47/1479). The HRs for tramadol in comparison with hydrocodone for all and serious events were 2.98 (2.03‐4.39) and 2.94 (1.81‐4.75), respectively. Increased risk for tramadol was consistently present when the adverse events were restricted to those with neurologic‐respiratory depression/other symptoms of possible overdose. Conclusion In adolescents without cancer or other severe conditions prescribed short‐acting opioids, the incidence of both all opioid‐related adverse events and more serious events with opioid‐related escalation of care, hospitalization, or death was consistently greater for tramadol than for hydrocodone.

Hospitalizations for opioid‐related overdose and timing of concurrent opioid and benzodiazepine use: A nested case‐control study

“…Elucidating the risk of opioid‐related overdose based on levels of recency was done to examine the relevance of a look‐back time period for monitoring concurrent use in the previous 90 days. To account for as needed use of opioids and BZDs, sensitivity analyses were conducted to extend prescription days supply by 15%, 30%, 50%, and 14 days 21 . Daily dose of concurrent use was calculated based on average Morphine Milligram Equivalents (MME/day) 22 and lorazepam equivalents per day 23 in the 90 days prior to opioid‐related overdose.…”

Medical prescription forms of opioid cough suppressants falsified by the patients before and after they switched from over‐the‐counter to prescription‐only in France

“…Nonmedical use of codeine has been demonstrated for years, and the first descriptions of cases of serious adverse reactions or fatalities attributed to codeine pills or even cough syrup date from the 1970s 24,25 . The incidence of codeine‐related adverse events in adolescents was found to be 91.2 per 10 000 person‐years in the US State of Tennessee 26 . The age‐standardized death rate due to drug dependence and substance‐use disorders in adolescents and young adults appears to have decreased overall in the World Health Organization European region, from 0.6 in 2005 to 0.2 in 2015 per 100 000 population 27 .…”

Trends in National Opioid Prescribing for Dental Procedures among Medicaid Patients

“…18 Hydrocodone, oxycodone, codeine, and tramadol are associated with high incidence of opioid-related adverse effects. 19 Tramadol was associated with higher rates of hospitalization, a need for escalated care, and death than other medications, particularly among adolescents. 19 Due to the associated medical complications of both codeine and tramadol, the Food and Drug Administration on April 20, 2017, issued guidance recommending no use of either medication in children younger than twelve.…”

“…19 Tramadol was associated with higher rates of hospitalization, a need for escalated care, and death than other medications, particularly among adolescents. 19 Due to the associated medical complications of both codeine and tramadol, the Food and Drug Administration on April 20, 2017, issued guidance recommending no use of either medication in children younger than twelve. 20 Given the stark social and economic costs and the higher likelihood of opioid use disorder and mortality, it is imperative to understand the impact and role of dentists and associated prescribing trends within the child and the non-elderly adult populations, especially for those receiving Medicaid, the insurance program that covers those among the most vulnerable in society.…”