FDA Initiative for Drug Facts Label for Over-the-Counter Naloxone

N Engl J Med. 2020 May 28;382(22):2129-2136. doi: 10.1056/NEJMsa1912403.


Background: The opioid crisis highlights the need to increase access to naloxone, possibly through regulatory approval for over-the-counter sales. To address industry-perceived barriers to such access, the Food and Drug Administration (FDA) developed a model drug facts label for such sales to assess whether consumers understood the key statements for safe and effective use.

Methods: In this label-comprehension study, we conducted individual structured interviews with 710 adults and adolescents, including 430 adults who use opioids and their family and friends. Eight primary end points were developed to assess user comprehension of each of the key steps in the label. Each of these end points included a prespecified target threshold ranging from 80 to 90% that was evaluated through a comparison of the lower boundary of the 95% exact confidence interval.

Results: The results for performance on six primary end points met or exceeded thresholds, including the steps "Check for a suspected overdose" (threshold, 85%; point estimate [PE], 95.8%; 95% confidence interval [CI], 94.0 to 97.1) and "Give the first dose" (threshold, 85%; PE, 98.2%; 95% CI, 96.9 to 99.0). The lower boundaries for four other primary end points ranged from 88.8 to 94.0%. One exception was comprehension of "Call 911 immediately," but this instruction closely approximated the target of 90% (PE, 90.3%; 95% CI, 87.9 to 92.4). Another exception was comprehension of the composite step of "Check, give, and call 911 immediately" (threshold, 85%; PE, 81.1%; 95% CI, 78.0 to 83.9).

Conclusions: Consumers met thresholds for sufficient understanding of six of eight components of the instructions in the drug facts label for naloxone use and came close on two others. Overall, the FDA found that the model label was adequate for use in the development of a naloxone product intended for over-the-counter sales.

MeSH terms

  • Adolescent
  • Adult
  • Analgesics, Opioid / poisoning*
  • Comprehension*
  • Drug Labeling* / legislation & jurisprudence
  • Drug Overdose / drug therapy*
  • Drug Overdose / therapy
  • Government Regulation
  • Humans
  • Interviews as Topic
  • Naloxone / therapeutic use*
  • Narcotic Antagonists / therapeutic use*
  • Nonprescription Drugs / therapeutic use*
  • United States
  • United States Food and Drug Administration


  • Analgesics, Opioid
  • Narcotic Antagonists
  • Nonprescription Drugs
  • Naloxone