Naloxone Co-Dispensing with Opioids: a Cluster Randomized Pragmatic Trial

Background Although naloxone prevents opioid overdose deaths, few patients prescribed opioids receive naloxone, limiting its effectiveness in real-world settings. Barriers to naloxone prescribing include concerns that naloxone could increase risk behavior and limited time to provide necessary patient education. Objective To determine whether pharmacy-based naloxone co-dispensing affected opioid risk behavior. Secondary objectives were to assess if co-dispensing increased naloxone acquisition, increased patient knowledge about naloxone administration, and affected opioid dose and other substance use. Design Cluster randomized pragmatic trial of naloxone co-dispensing. Setting Safety-net health system in Denver, Colorado, between 2017 and 2020. Participants Seven pharmacies were randomized. Pharmacy patients ( N =768) receiving opioids were followed using automated data for 10 months. Pharmacy patients were also invited to complete surveys at baseline, 4 months, and 8 months; 325 survey participants were enrolled from November 15, 2017, to January 8, 2019. Intervention Intervention pharmacies implemented workflows to co-dispense naloxone while usual care pharmacies provided usual services. Main Measures Survey instruments assessed opioid risk behavior; hazardous drinking; tobacco, cannabis, and other drug use; and knowledge. Naloxone dispensings and opioid dose were evaluated using pharmacy data among pharmacy patients and survey participants. Intention-to-treat analyses were conducted using generalized linear mixed models accounting for clustering at the pharmacy level. Key Results Opioid risk behavior did not differ by trial group ( P =0.52; 8-month vs. baseline adjusted risk ratio [ARR] 1.07; 95% CI 0.78, 1.47). Compared with usual care pharmacies, naloxone dispensings were higher in intervention pharmacies (ARR 3.38; 95% CI 2.21, 5.15) and participant knowledge increased ( P =0.02; 8-month vs. baseline adjusted mean difference 1.05; 95% CI 0.06, 2.04). There was no difference in other substance use by the trial group. Conclusion Co-dispensing naloxone with opioids effectively increased naloxone receipt and knowledge but did not increase self-reported risk behavior. Trial Registration Registered at ClinicalTrials.gov ; Identifier: NCT03337100