Assessment of Potentially Inappropriate Prescribing of Opioid Analgesics Requiring Prior Opioid Tolerance.

Importance: Opioid-tolerant only (OTO) medications, such as transmucosal immediate-release fentanyl products and certain extended-release opioid analgesics, require prior opioid tolerance for safe use, as patients without tolerance may be at increased risk of overdose. Studies using insurance claims have found that many patients initiating these medications do not appear to be opioid tolerant. Objectives: To measure prevalence of opioid tolerance in patients initiating OTO medications and to determine whether linked electronic health record (EHR) data contribute evidence of opioid tolerance not found in insurance claims data. Design, Setting, and Participants: This retrospective cohort study used a national database of deidentified longitudinal health information, including medical and pharmacy claims, insurance enrollment, and EHR data, from January 1, 2007, to December 31, 2016. Data included 131 756 US residents with at least 183 days of continuous enrollment in commercial or Medicare Advantage insurance (including medical and pharmacy benefits) who had received an OTO medication and who had no inpatient stays in the 30 days prior to starting an OTO medication; of these, 20 044 individuals had linked EHR data within the prior 183 days. Data were analyzed from July 1, 2017, to August 31, 2018. Exposures: Initiating an OTO medication. Main Outcomes and Measures: Prior opioid tolerance demonstrated through pharmacy fills or EHR data on prescriptions written. Results: Among 153 385 OTO use episodes identified, 89 029 (58.0%) occurred among women, 62 900 (41.0%) occurred among patients with Medicare Advantage insurance, 39 394 (25.7%) occurred in the Midwest, 17 366 (11.3%) occurred in the Northeast, 73 316 (47.8%) occurred in the South, and 23 309 (15.2%) occurred in the West. Less than half of use episodes (73 117 episodes [47.7%]) involved patients with evidence in claims data of opioid tolerance prior to initiating therapy with an OTO medication, including 31 392 of 101 676 episodes (30.9%) involving transdermal fentanyl, 1561 of 2440 episodes (64.0%) involving transmucosal fentanyl, 36 596 of 43 559 episodes (84.0%) involving extended-release oxycodone, and 3568 of 5710 episodes (62.5%) involving extended-release hydromorphone. Among 20 044 OTO use episodes with linked EHR and claims data, less than 1% of OTO episodes identified in claims had evidence of opioid tolerance in structured EHR data that was not present in claims data (108 episodes [0.5%]). After limiting the sample to OTO episodes identified in claims with a matching OTO prescription within 14 days in the structured EHR data, only 40 of 939 episodes (4.0%) occurred among patients with evidence of tolerance that was not present in claims data. Conclusions and Relevance: This cohort study found that most patients initiating OTO medications did not have evidence of prior opioid tolerance, suggesting they were at increased risk of opioid-related harms, including fatal overdose. Data from EHRs did not contribute substantial additional evidence of opioid tolerance beyond the data found in prescription claims. Future research is needed to understand the clinical rationale behind these observed prescribing patterns and to quantify the risk of harm to patients associated with potentially inappropriate prescribing.

Trends and Rapidity of Dose Tapering Among Patients Prescribed Long-term Opioid Therapy, 2008-2017.

Importance: A 2016 Centers for Disease Control and Prevention prescribing guideline cautioned against higher-dose long-term opioid therapy and recommended tapering daily opioid doses by approximately 10% per week if the risks outweigh the benefits. Warnings have since appeared regarding potential hazards of rapid opioid tapering. Objectives: To characterize US trends in opioid dose tapering among patients prescribed long-term opioids from 2008 to 2017 and identify patient-level variables associated with tapering and a more rapid rate of tapering. Design, Setting, and Participants: This retrospective cohort study used deidentified medical and pharmacy claims and enrollment records for 100 031 commercial insurance and Medicare Advantage enrollees, representing a diverse mixture of ages, races/ethnicities, and geographical regions across the United States. Adults with stable, higher-dosage (mean, ≥50 morphine milligram equivalents [MMEs]/d) opioid prescriptions for a 12-month baseline period and 2 or more months of follow-up from January 1, 2008, to December 31, 2017, were included in the study. Main Outcomes and Measures: Tapering was defined as 15% or more relative reduction in mean daily MME during any of 6 overlapping 60-day windows within a 7-month follow-up period. The rate of tapering was computed as the maximum monthly percentage dose reduction. Results: Among the 100 031 participants (53 452 [53.4%] women; mean [SD] age, 57.6 [11.8] years), from 2008 to 2015, the age- and sex-standardized percentage of patients tapering daily opioid doses increased from 10.5% to 13.7% (adjusted incidence rate ratio [aIRR] per year, 1.05 [95% CI, 1.05-1.06]) before increasing to 16.2% in 2016 and 22.4% in 2017 (aIRR in 2016-2017 vs 2008-2015, 1.20 [95% CI, 1.16-1.25]). Patient-level covariates associated with tapering included female sex (aIRR, 1.13 [95% CI, 1.10-1.15]) and higher baseline dose (aIRR for ≥300 MMEs/d vs 50-89 MMEs/d, 2.57 [95% CI, 2.48-2.65]). Among patients tapering daily opioid doses, the mean (SD) maximum dose reduction was 27.6% (17.0%) per month, and 18.8% of patients had a maximum tapering rate exceeding 40% per month (ie, faster than 10% per week). More rapid dose reduction was associated with 2016-2017 vs 2008-2015 (adjusted difference, 1.4% [95% CI, 0.8%-2.1%]) and higher baseline dose (adjusted difference, 2.7% [95% CI, 2.2%-3.3%] for 90-149 vs 50-89 MMEs/d). Conclusions and Relevance: Patients using long-term opioid therapy are increasingly undergoing dose tapering, particularly women and those prescribed higher doses; in addition, dose tapering has become more common since 2016. Many patients undergoing tapering reduce daily doses at a rapid maximum rate.