"We contribute nationally representative evidence to help answer each of these questions, including wholesale pricing data from a proprietary drug sales database spanning January 2006 to February 2017. We find that all formulations of naloxone increased in price since 2006 except for Narcan Nasal Spray. These cumulative increases totaled 2281% for the 0.4 MG single-dose products, 244% for the 2 MG single-dose products, 3797% for the 4 MG multi-dose products, and 469% for the 0.4 MG Evzio auto-injector.

"This large multicentre, randomised, controlled, comparative effectiveness trial had five major findings. First, it was more difficult to start XR-NTX [Extended-release naltrexone] treatment than BUP-NX [sublingual buprenorphine-naloxone] treatment: 28% dropped out of treatment before XR-NTX induction versus only 6% before BUP-NX induction. Second, nearly all induction failures had early relapse. Third, in the intention-to-treat population of all patients who were randomly assigned, XR-NTX had lower relapse-free survival than BUP-NX, directly related to early induction failure.

"Results
"By 2014, 30 states had a naloxone access and/or Good Samaritan law. States with naloxone access laws or Good Samaritan laws had a 14% (p = 0.033) and 15% (p = 0.050) lower incidence of opioid-overdose mortality, respectively. Both law types exhibit differential association with opioid-overdose mortality by race and age. No significant relationships were observed between any of the examined laws and non-medical opioid use.

"• Naloxone access laws that ease restrictions on naloxone possession and distribution are associated with a 20% reduction overdose deaths among African-Americans.
"• Good Samaritan laws, providing immunity from prosecution for those calling emergency services, are associated with broad reductions in overdose deaths, reducing overdose deaths by 13% overall.
"• None of these harm reduction measures result in increase in opioid or heroin use.

"Naloxone is the most common antidote used for overdoses. It is normally ambulance personnel who administer naloxone in connection with opioid overdoses, and doses are administered by intramuscular or intravenous injection. It is now being discussed whether naloxone in the form of a mouth spray should be available to others as well, as first aid for someone who has overdosed
until the ambulance arrives."

"Naloxone distribution was cost-effective in our base-case and all sensitivity analyses, with incremental costs per QALY [Quality-Adjusted Life-Year] gained much less than $50 000 (Table 2 and Appendix Figure 3, available at www.annals.org; see Appendix Table 3, available at www.annals.org, for detailed results of selected analyses). Cost-effectiveness was similar at starting ages of 21, 31, and 41 years; the greater QALY gains of younger persons were roughly matched by higher costs.

"Naloxone distribution to heroin users would be expected to reduce mortality and be cost-effective even under markedly conservative assumptions of use, effectiveness, and cost. Although the absence of randomized trial data on naloxone distribution and reliance on epidemiologic data increase the uncertainty of results, there are few or no scenarios in which naloxone would not be expected to increase QALYs [Quality-Adjusted Life-Years] at a cost much less than the standard threshold for cost-effective health care interventions.

"The heart of the challenge is the possibility that things could be different: overdose is a public health problem that can be solved. Unlike many of the other leading causes of death, death from opioid overdose is almost entirely preventable,²¹ and preventable at a low cost.²² Opioids kill by depressing respiration, a slow mode of death that leaves plenty of time for effective medical intervention.²³ Overdose is rapidly reversed by the administration of a safe and inexpensive drug called naloxone.

"Naloxone distribution programs in the US are ongoing in Chicago, Baltimore, San Francisco, New Mexico and New York City. Additional community-based organizations interested in minimizing the adverse consequences of drug use in several cities in the US, including Los Angeles, Providence, Pittsburgh and Boston, are in the process of planning and developing naloxone administration programs for drug users."

"This pilot trial is the first in North America to prospectively evaluate a program of naloxone distribution to IDUs [Injection Drug Users] to prevent heroin overdose death. After an 8-hour training, our study participants' knowledge of heroin overdose prevention and management increased, and they reported successful resuscitations during 20 heroin overdose events. All victims were reported to have been unresponsive, cyanotic, or not breathing, but all survived. These findings suggest that IDUs can be trained to respond to heroin overdose by using CPR and naloxone, as others have reported.