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Reducing the harm of opioid overdose with the safe use of naloxone: a pharmacologic review

Introduction: Opioid overdose fatality has increased threefold since 1999. As a result, prescription drug overdose surpassed motor vehicle collision as the leading cause of unintentional injury-related death in the USA. Naloxone, an opioid antagonist that has been available for decades, can safely reverse opioid overdose if used promptly and correctly. However, clinicians often overestimate the dose of naloxone needed to achieve the desired clinical outcome, precipitating acute opioid withdrawal syndrome (OWS). Areas covered: This article provides a comprehensive review of naloxone’s pharmacologic properties and its clinical application to promote the safe use of naloxone in acute management of opioid intoxication and to mitigate the risk of precipitated OWS. Available clinical data on opioid-receptor kinetics that influence the reversal of opioid agonism by naloxone are discussed. Additionally, the legal and social barriers to take home naloxone programs are addressed. Expert opinion: Naloxone is an intrinsically safe drug, and may be administered in large doses with minimal clinical effect in non-opioid-dependent patients. However, when administered to opioid-dependent patients, naloxone can result in acute opioid withdrawal. Therefore, it is prudent to use low-dose naloxone (0.04 mg) with appropriate titration to reverse ventilatory depression in this population.