Quality Assessment of Expired Naloxone Products from First-Responders' Supplies

Objective: Naloxone is an opioid receptor antagonist that reverses life-threatening effects of opioid overdose. Since the 1970s, naloxone products have been developed as injectable solutions, and more recently as nasal sprays. Naloxone products have saved many lives in emergency settings. These products are routinely carried by public safety first-responders including fire fighters (FF), law enforcement officers (LEO), and emergency medical services (EMS). Now, they are also distributed through community access programs to the public. While public safety medications are monitored, those publically distributed are not, so expired products can be possibly found on-hand in an emergency. This study analyzed the quality and stability of expired Naloxone HCl Solutions for Injection, to assess their remaining efficacies and potential risks. Methods: The samples were collected from EMS or law enforcement training supplies and expired returns, with expiration dates ranging from 1990 to 2018. Using standardized techniques, the remaining naloxone was quantified, and the main degradation products, nornaloxone (also known as noroxymorphone) and other possible species, were monitored and quantified systematically. Results: Most tested samples were found containing more than 90% of labeled naloxone, including those stored for nearly 30 years. The naloxone degradation was slow, but generally correlated with storage time length. There was no significant amount of degradation products detected across all samples. Nornaloxone was detected from some older samples, but all less than 1%. Therefore, although it is an opioid agonist, the risk caused by nornaloxone should be low. Conclusion: This quality assessment demonstrates that expired naloxone products may still meet USP standards, even after many years. Further pharmaceutical, clinical, and regulatory investigation should be conducted to confirm our findings, especially for new naloxone products with different formulations and routes of administration. Extending the shelf-life of naloxone products may have important financial and public health consequences in addressing future drug shortages and meeting the needs for this critical drug.