Model simulations were performed using a validated translational model1 developed by the Division of Applied Regulatory Science in the US Food and Drug Administration's Center for Drug Evaluation and Research. In the present study, this translational model was further expanded with data from pharmacokinetic and pharmacodynamic studies with OPVEE2,3 and IN naloxone pharmacokinetic data.2 Simulations were conducted in 2000 virtual patients. Following an IV dose of 2.97 mg fentanyl that resulted in a 78% incidence of cardiac arrest in chronic opioid users, a single administration of 4 mg IN naloxone reduced this rate to 47% while a single dose of IN OPVEE reduced this rate to 12%. Four simultaneous doses of 4 mg IN naloxone were needed to lower the incidence of cardiac arrest to 17% which was comparable to that observed following a single dose of OPVEE (12%).
Simulations in opioid naïve individuals illustrated the same trend, although a higher incidence of cardiac arrest was predicted in this population given the lack of tolerance to the respiratory effects of opioids. Simulation of an IV fentanyl overdose (2.97 mg) in opioid naïve individuals led to an incidence of cardiac arrest of 90%, which was reduced to 26% with IN OPVEE and to 68% after 4 mg IN naloxone, respectively.
More than 78,200 fatal opioid overdoses in the US were reported in the one year ending December 2023, with almost 92% (71,821) linked to synthetic opioids.4 According to The State Unintentional Drug Overdose Reporting System (SUDORS), the percentage of overdose deaths in which naloxone was administered (22% in the US in 2022)5, suggests that naloxone might not have been administered fast enough or at sufficient dosage.
"These modeling data are relevant considering today's overdose epidemic with increasing prevalence of overdoses from illicitly manufactured synthetic opioids, which can be extremely difficult to reverse6," said Christian Heidbreder, PhD, Chief Scientific Officer, Indivior, Inc. "These simulated data serve two purposes. First, they quantify the challenge of effectively reversing a synthetic opioid overdose. Second, these data inform the approach for first responders (e.g., police, fire and rescue personnel, friends and family of the overdose victim) in a community setting that does not benefit from the ventilatory support available in an Emergency Department. Without adequate ventilatory support, there is a limited time window before hypoxic injury is irreversible and cardiac arrest occurs; this can happen extremely rapidly with fentanyl and other synthetic opioids."
About Indivior:
Indivior is a global pharmaceutical company working to help change patients' lives by developing medicines to treat substance use disorders (SUD), opioid overdose and serious mental illnesses. Our vision is that all patients around the world will have access to evidence-based treatment for the chronic conditions and co-occurring disorders of SUD. Indivior is dedicated to transforming SUD from a global human crisis to a recognized and treated chronic disease. Building on its global portfolio of opioid use disorder treatments, Indivior has a pipeline of product candidates designed to both expand on its heritage in this category and potentially address other chronic conditions and co-occurring disorders of SUD. Headquartered in the United States in Richmond, VA, Indivior employs more than 1,100 individuals globally and its portfolio of products is available in 37 countries worldwide.
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