Opioid tolerance and clinically recognized opioid poisoning among patients prescribed extended-release long-acting opioids

Abstract

Background: In recognition of potential for increased overdose risk, drug labels for extended-release and long-acting (ER/LA) opioids emphasize the need for established opioid tolerance prior to initiating high dosages.

Objectives: Describe the proportion of patients with opioid tolerance prior to initiation of 90 morphine milligram equivalents (MME) ER/LA opioids and examine subsequent risk of opioid poisoning.

Methods: We used Truven Health Analytics' MarketScan Databases (2006-2015) to identify patients initiating ER/LA opioids ≥90 MME. We examined prescription histories and describe the proportion of initiators with opioid tolerance (defined as ≥7 days of 60 MME in the prior 14 days). We adjusted for age, sex, year of initiation, and baseline comorbidities using inverse probability of treatment weighted Cox proportional hazards models. We estimated adjusted hazard ratios and 95% confidence intervals for the effect of opioid tolerance on the risk of clinically recognized opioid poisoning (based on diagnosis codes) in specific periods (0-7, 8-30, 31-90, and 91-365 days) following initiation.

Results: Among 372 038 initiators, 38% did not meet opioid tolerance criteria. The proportion of nontolerant initiators was highest among those initiating methadone (44%) and fentanyl (42%). Nontolerant patients were 37% more likely to be diagnosed with opioid poisoning (adjusted hazard ratios = 1.37 [1.07, 1.76]) in the week following ER/LA initiation.

Conclusions: Over one-third of patients initiating ≥90 MME ER/LA opioids did not have evidence of opioid tolerance. The 7 days following high dose ER/LA initiation may represent a high-risk period for clinically diagnosed opioid poisoning in patients who do not have prior opioid tolerance.

Keywords: extended-release long-acting opioids; opioid poisoning; opioid tolerance; pharmacoepidemiology.