Indivior PLC announced results from Buprenorphine-Fentanyl interaction study in PLOS ONE. Provisional data from the centers for disease control and prevention (CDC) estimate there were 101,263 predicted drug overdose deaths in the U.S. during the 12 month period ended June 2021, with approximately 76,002 and 64,977 of these deaths attributable to opioids and synthetic opioids (excluding methadone), respectively.2 The majority of opioid-related overdose deaths in the United States are the result of synthetic opioids (mainly fentanyl and illicit fentanyl analogs) that are more potent than heroin and that can unexpectedly cause respiratory depression by being ingested as a substitute for heroin or with drugs such as prescription opioids, cocaine, methamphetamine or nonopioids with sedative or hypnotic properties (e.g., benzodiazepines, gabapentin, and xylazine)3,4,5 6. In the 12-month period ended in June 2021, 75% of the estimated 101,000 drug overdose deaths were driven by opioids2 an average of more than 200 deaths per day, double the number of fatalities resulting from motor vehicle traffic crashes.8. This clinical pharmacology study, which was conducted in a medical center anesthesiology department, was designed to assess the competitive interaction of fentanyl and buprenorphine on respiratory depression. It evaluated the ability of treatment-relevant plasma concentrations of buprenorphine to prevent respiratory depression and resultant apnea (cessation of breathing) induced by escalating doses of fentanyl. The primary endpoint of the study was to measure the effects of escalating fentanyl dosing on respiratory depression as measured by minute ventilation (VE) under elevated carbon dioxide (CO2) conditions. VE is the volume of gas inhaled or exhaled from a person's lungs per minute. VE is an important parameter in respiratory medicine due to its relationship with blood carbon dioxide (CO2) levels. The maximum decrease in VE, induced by the highest dose of fentanyl, was nearly 60% less with a steady-state plasma buprenorphine concentration of 2.0 ng/mL compared with placebo (33.7% vs 82.3% decrease in VE, respectively). The risk of experiencing apnea requiring verbal stimulation after fentanyl
dosing was significantly lower with buprenorphine than with placebo (p=0.001).1.