It is also difficult to determine if other non-opioid substances are contributing to a drug overdose, for which naloxone is not an effective treatment. Rather a central concern for treating fentanyl/fentanyl analog overdose is the rapidity of overdose onset and the narrow window for treatment. No well-controlled studies have been conducted to test this argument, and the current literature provides limited evidence to suggest that naloxone is ineffective against fentanyl or fentanyl analog overdose. ![]() The argument that naloxone is not efficacious against fentanyl and fentanyl analogs rests on case studies, retrospective analyses of community outbreaks, pharmacokinetics, and pharmacodynamics. We also highlight current advances in overdose treatments and technologies that have been tested in humans. This narrative review provides a brief overview of naloxone, including its history and pharmacology, and the evidence regarding naloxone efficacy against fentanyl and fentanyl analogs. Naloxone is the primary opioid overdose reversal agent, but concern has been raised that naloxone is not efficacious against the pervasive illicit high potency opioids (i.e., fentanyl and fentanyl analogs). ![]() Opioid overdose deaths reached a new record of over 74,000 in a 12-month period ending April 2021. The USA has recently entered the third decade of the opioid epidemic.
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