Mike Heller, BS Asif Ilyas, MD, MBA, FACS
Naloxone (Narcan) is an opioid receptor antagonist that can be used to rapidly reverse the effects of opioids such as depressed breathing.
Increasing the availability of Naloxone along with providing the appropriate overdose reversal training to individuals at risk of experiencing or witnessing an opioid overdose is an effective way to reduce unintentional deaths due to opioids.
States with the implementation of Naloxone standing orders have shown a 79% increase in total Naloxone dispensed at retail pharmacies.
States with mandated co-prescribing requirements experienced a 285% increase in the total number of Naloxone doses dispensed.
First responder training in Naloxone administration has resulted in decreased opioid-related deaths.
40.3% of high school nurses surveyed in North/South Carolina reported an encounter with a student currently on prescription opioids, and only 3.6% reported immediate availability of Naloxone in their building.
As the opioid addiction crisis continues to worsen throughout communities nationwide, it is important to understand the guidelines, utilization, and role of Naloxone (Narcan) in combatting this epidemic. Naloxone is a life-saving medication designed to rapidly reverse the effects of opioids in a patient who is overdosing (1). It reverses overdoses through its action as an opioid receptor antagonist (1). In attempts to mitigate the opioid crisis, states have begun to change laws and regulations surrounding naloxone access. Currently, all 50 states, including DC and Puerto Rico, allow individuals to obtain naloxone without a prescription from a healthcare provider in some capacity (3). Many states are also beginning to push towards mandated co-prescribing of naloxone by physicians prescribing opioids (5), along with naloxone training for all first responders (6) and high school nurses (8,9). The common goal between these changes is focused on increasing the amount of naloxone dispensed throughout communities and professions. Easier access to naloxone along with a heightened awareness about its importance in reversing an overdose increases the potential for many lives to be saved, especially of those in communities being hit hardest by a local opioid crisis. Overdose reversal through naloxone provides individuals who are struggling with an opioid use disorder another opportunity to receive the medical treatment, help, and resources they may need. In this analysis, a review of nationwide access to naloxone will be reviewed.
Naloxone Access Without a Prescription
Since 2010, naloxone standing orders and third-party prescribing provisions have increased dramatically across the country (4). On October 28th, 2015, the Pennsylvania Secretary of Health, Dr. Rachel Levine signed a statewide naloxone standing order (2). The standing order serves as a prescription for anybody to obtain naloxone from a pharmacy with the purpose of ensuring all residents of the Commonwealth of Pennsylvania at risk of opioid overdose, or family members, friends, and other persons in a position to potentially assist with reversing an opioid overdose, the ability to obtain Naloxone (2). Since the first statewide standing order of naloxone in 2010, there have been 32 additional states who have signed a standing order into place. Jing Xu et al performed a study to determine the impact naloxone laws have had on total naloxone dispensing in retail pharmacies across the United States from 2007 to 2016. The results showed dramatic increases in total naloxone orders dispensed, jumping from 1,488 in 2007 to 147,457 in 2016 (4). Furthermore, their model showed that states with implementation of naloxone access laws were associated with an average increase of 78 Narcan prescriptions dispensed per quarter year, which is an average 79% increase. (4)
FIGURE 1: Visualization of Naloxone Access in the US per State as of August 2020. Reprinted from Legislative Analysis and Public Policy Association. https://legislativeanalysis.org/wp-content/uploads/2020/10/Naloxone-summary-of-state-laws-FINAL-9.25.2020.pdf
Figure 2: Changes in Total Naloxone Dispensed per year from 2007 – 2016. The dramatic increase occurred from 2015 – 2016. Reprinted from Jing Xu et al. State naloxone access laws are associated with an increase in the number of naloxone prescriptions dispensed in retail pharmacies. Drug and Alcohol Dependence. 2018; 189: 37-41
Physician Co-Prescribing of Naloxone with Opioids
Another effective way to promote naloxone dispensing is the adoption of co-prescribing requirements of naloxone by physicians when writing an opioid prescription. This conversation can provide the patient with the necessary awareness of the importance of closely monitoring their usage of opioids. Currently, there are nine states with a mandated co-prescription requirement (5). The guidelines for when co-prescription is required varies by state and depends on the amount of morphine milligram equivalents (MME) being prescribed by the doctor, traumatic injury severity score, and benzodiazepine usage. (5). Green et al examined the effects of co-prescribing requirements on the total number of naloxone dispensed in pharmacies of the first 5 states to adopt such laws (Arizona, Florida, Rhode Island, Vermont, and Virginia). They used data from CVS Pharmacies between 2014 to 2018 to compare the number of total naloxone doses dispensed because of physician prescriptions for 90 days before and after co-prescribing mandates took place. Their results showed a substantial increase in naloxone doses dispensed due to traditional prescriptions by a physician, from 5,413 to 20,873, a 285% increase (5).
Another important result they found was the number of different naloxone prescribers increased from 1,028 before the co-prescribing mandate to 4,285 after 90 days of the initiation of the mandates, which amounts to 317% increase (5). Since the implementation of the co-prescribing mandates, there has also been a significant shift in percentages of naloxone prescribed by specialty in the 5 states studied. Physician assistants (5.3% to 12.4%) and internal medicine physicians (5.0% to 9.1%) showed the largest increases, while nurse practitioners (24.3% to 12.9%) and anesthesiologists/pain medicine specialists (23.4% to 17.3%) experienced the largest decrease in the percentage of naloxone prescribed (5).
Figure 3: Visualization of Co-Prescription Requirements in the US per State as of August 2020. Reprinted from Legislative Analysis and Public Policy Association. https://legislativeanalysis.org/wp-content/uploads/2020/10/Naloxone-summary-of-state-laws-FINAL-9.25.2020.pdf
Training of First Responders in Naloxone Administration and Opioid Overdose Reversal
Another strategy many larger cities have implemented is providing naloxone education and training for all potential first responders (EMS, fire, and police). Rando et al performed a prospective interventional study to determine the effectiveness of police officer naloxone training in decreasing opioid overdose rates in Lorain County, Ohio from January 2011 to October 2014. Opioid overdose deaths per quarter were increasing significantly in Lorain County prior to the police officer naloxone training initiation. The average deaths per quarter year were 5.5 for 2011, 15.3 for 2012, and 16.3 for the first three quarters of 2013 (6). Following the initiation of the police officer naloxone training program, opioid overdose deaths consistently decreased each quarter with an average of 13.4 deaths per quarter (6). Naloxone training for EMS personnel has been implemented in Philadelphia since early 2014, while Philadelphia Police Department naloxone training and carrying did not take place until the 3rd quarter of 2016, right around the time when overdose death rates began to increase dramatically due to the increased presence of fentanyl in street heroin. Data from Philadelphia Emergency Medical Services Center showed a consistent increase in the number of Narcan doses administered by both EMS and Philadelphia police from quarter 3 of 2016 until quarter 2 of 2017, where doses administered peaked at 1,836 and 197, respectively (7).
Figure 4: Number of Naloxone Doses Administered by Philadelphia EMS, Police Department, and SEPTA Employees from 2014 – 2020. Reprinted from Philadelphia Emergency Medical Services; Delaware Valley Intelligence Center. https://www.substanceusephilly.com/naloxone
Naloxone Supplies and Training for High School Nurses
Increasing naloxone supplies and overdose training for school nurses is another lifesaving change that could be implemented nationwide to help decrease the number of opioid overdose deaths in teenagers. A cross-sectional study published by McDonald et al collected data from March 2018 to June 2018 in an attempt to understand the current standing of naloxone availability in high schools across Pennsylvania and the reasons, if any, for not having a supply. Of the 362 school nurses who met inclusion criteria, 53.6% reported a naloxone supply in their building, and 5.2% of those with a naloxone supply in their building reported a past administration of their naloxone on a student who was overdosing (8). A similar study published by Sharp et al was interested in assessing the rates of school nurses in North and South Carolina who have encountered students with opioid prescriptions. Of the 633 school nurses sampled in the study, 40.3% of them reported an encounter with a student who was prescribed opioids but only 3.6% of them had naloxone available in their building (9). Moreover, 83.9% of the nurses involved in the study reported interest in opioid-related training for staff, and 69.9% believe that opioid education to the students would be beneficial (9).
Recent Changes & Future Direction
As lifesaving as naloxone can be for so many people suffering from opioid overdose or abuse, it does not do any good for those who are unaware of it, do not know how to use it, do not have a prescription for it, or cannot afford to pay for it. An initiative to resolve this issue took place in 2020 when a Philadelphia based naloxone distribution program, SOL Collective, and the Philadelphia Department of Public Health, partnered with a national harm reduction program, NEXT Distro, to provide Philadelphia residents an opportunity to sign up online for free naloxone doses mailed directly to their home after watching a short overdose training video and questionnaire (10). From March 2020 – January 2021, there were 422 naloxone requests through the program in Philadelphia (11). French et al were interested in studying the reported barriers to naloxone access from the individuals who requested the naloxone doses (12). Within their results, they found that the most significant barriers included COVID quarantine (25.1%), lack of knowledge about the access (13.2%), and cost (11.2%) (12). They also found that individuals who were categorized as a higher risk for overdosing or witnessing an overdose heard about the naloxone mailing program more often through an active online search when compared to the individuals who were categorized as lower risk for an overdose or witnessing one (21.4% vs 8.8%). Conversely, those in the lower risk group showed higher reports of hearing about the program through word of mouth compared to those in the higher risk group (40.9% vs 19.8%) (12). Interpreting the data from this study reveals the impactful work done by SOL Collective and NEXT Distro which has addressed the lack of affordability and accessibility of naloxone, an ongoing issue that has been affecting many families in Philadelphia community since the start of the opioid crisis.
Access to naloxone through non-prescription use, co-prescribing with opioids, training, and access to it by first responders, and access to it for school nurses have been increasing across the country. This increase in the availability and access to naloxone has been shown to be an effective strategy to mitigate opioid-related deaths and is an effective opioid harm reduction tool.
NIDA. Naloxone DrugFacts. National Institute on Drug Abuse website. https://www.drugabuse.gov/publications/drugfacts/naloxone. June 1, 2021 Accessed June 10, 2021.
Pennsylvania Department of Health. Naloxone Standing Order. https://www.health.pa.gov/topics/Documents/Opioids/General%20Public%20Standing%20Order.pdf. Accessed June 10, 2021
Legislative Analysis and Public Policy Association. Naloxone Access: Summary of State Laws. https://legislativeanalysis.org/wp-content/uploads/2020/10/Naloxone-summary-of-state-laws-FINAL-9.25.2020.pdf. September 2020. Accessed June 11, 2021.
Xu J, Davis CS, Cruz M, Lurie P. State naloxone access laws are associated with an increase in the number of naloxone prescriptions dispensed in retail pharmacies. Drug and Alcohol Dependence. 2018; 189: 37-41. doi: 10.1016/j.drugalcdep.2018.04.020
Green TC, Davis C, Xuan Z, et al. Laws mandating coprescription of naloxone and their impact on naloxone prescription in five US states. American Journal of Public Health. 2020; 110: 881-887. doi: 10.2105/AJPH.2020.305620