Author: [AUTHOR] Published on 3/10/2023 5:00:00 AM

FDA Addresses the Opioid Crisis Through Proactive and Innovative Regulatory Research

In 2021, 106,699 drug overdose deaths occurred in the United States. Approximately 75% of these deaths involved an opioid, and the rate of deaths due to opioids is on the rise.[1] While the US Food and Drug Administration (FDA) has recently approved multiple anti-opioid, naloxone products, significant scientific and operational challenges in tackling this growing public health crisis remain. Two FDA articles published in December 2022, Assessing the Impact of Opioid Overdose and Opioid Antagonist Dosing to Support Medical Product Development and Assessing the Respiratory Effects of Approved Opioid Products When Co-administered with Commonly Prescribed Drugs highlight the FDA’s collaborative and innovative research into the underlying biological and pharmacological pathways involved in respiratory depression due to opioids, prevention of possible overdose scenarios, and acceleration of fast-acting, safe, and effective naloxone treatments.

The FDA Impact Story article Assessing the Impact of Opioid Overdose and Opioid Antagonist Dosing to Support Medical Product Development, describes the challenges in dosing naloxone, an opioid antagonist, for the numerous prescription and illicit opioid compounds. To address this challenge, FDA developed, validated, and published a translational model constructed from available data that incorporates physiological information of how opioids and naloxone act in the body to predict responses in a variety of overdose and intervention scenarios. Based on FDA’s translational model of patient response to opioids and naloxone, CDER was able to approve a naloxone product as an emergency treatment for individuals who are over aged 12 years where use of high-potency opioids, such as fentanyl analogues, as a chemical weapon is suspected. This model also provides CDER scientists with a robust quantitative framework for evaluating dosing regimens of opioid receptor antagonists to reverse opioid-induced respiratory depression in a community setting, including for newly emerging synthetic opioids with limited clinical data.

The FDA Spotlight on CDER Science article Assessing the Respiratory Effects of Approved Opioid Products When Co-administered with Commonly Prescribed Drugs describes the Agency’s multi-step approach to understand if drugs other than benzodiazepines, when co-administered with opioid drugs, might also raise the risk of respiratory depression. Through literature and non-clinical studies, two drugs, paroxetine and quetiapine, were identified for further evaluation through a clinical trial. The clinical study demonstrated that paroxetine plus oxycodone significantly decreased mean hypercapnic ventilation compared to placebo plus oxycodone. These findings may have important clinical implications for patients on paroxetine (or, potentially, other antidepressant drugs) who concomitantly use opioids, but further research is needed. FDA researchers have initiated a separate clinical trial to further explore the observations with paroxetine and better understand the dosing effects on ventilation during paroxetine treatment and potentially related drugs.

To learn more about FDA’s work to address the evolving opioid crisis, see the Food and Drug Administration Overdose Prevention Framework and a recent perspective article on CDER’s Continued Efforts to Widen Naloxone Access. More FDA Impact Stories illustrating how regulatory science impacts the lives and health of people can be found at the FDA’s Impact Stories webpage. Learn more from CDER scientists describing scientific advancements aimed at improving drug development at FDA’s Spotlight on CDER Science webpage.

[1] National Institute on Drug Abuse. (February 9, 2023). Drug Overdose Death Rates. Retrieved March 1, 2023. https://nida.nih.gov/research-topics/trends-statistics/overdose-death-rates.

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This communication was prepared by Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDA.