1. Naloxone and You Ryan Feldman, PharmD, BCPS
Emergency Medicine Clinical Pharmacy Specialist
Poison Specialist

2. Disclosures
None

3. Educational Objectives
State
The purpose of Wisconsin act 115 and its impact on naloxone availability in the community.
Identify
Patients and caregivers who are candidates home naloxone prescriptions
Review
Teaching points for patient education after naloxone prescription
Discuss
Available community resources for naloxone attainment

4. Opioid Agonists Activates opioid receptors Central activation
Mu, Kappa, Delta
Central and Peripheral
Central activation
Analgesia
Sedation
Euphoria

5. Opioid Agonist Overdose
Excessive opioid receptor agonism
Occurrence:
Therapeutic use
Intentional abuse
Unintentional ingestion
Opioid Agonist Overdose
Reduced sensitivity to changes in O2 and CO2 outside of normal ranges
Decreased tidal volume and respiratory frequency
Respiratory depression and death due to hypoventilation
Reproduced from Alexander Y. Walley, MD, MSc, Epidemeology and Overdose Risk

6. Opioid Agonist Overdose
Excessive opioid receptor agonism
Can occur in:
Therapeutic use
Intentional abuse
Unintentional ingestion
Opioid Agonist Overdose
Reduced sensitivity to changes in O2 and CO2 outside of normal ranges
Decreased tidal volume and respiratory frequency
Respiratory depression and death due to hypoventilation
Reproduced from Alexander Y. Walley, MD, MSc, Epidemeology and Overdose Risk

7. Opioid Overdose Deaths in U.S. Quintupled 1999-2016
Source:
Drug overdose death rates in the United States have more than tripled since 1990 and have never been higher. In 2008, more than 36,000 people died from drug overdoses, and most of these deaths were caused by prescription drugs.4
4. CDC. Vital Signs: Overdoses of Prescription Opioid Pain Relievers—United States, MMWR 2011; 60: 1-6

8. Drug Overdose Deaths Outnumber Motor Vehicle Traffic Deaths 31 States, 2010
Slide from Chris Jones. Presented at APHA 2013.
More deaths from drug overdose
CDC National Vital Statistics System, Multiple Causes of Death. 2010

9. A Public Health Issue
Source- Wisconsin DHS: Select Opioid Related Mortality

10. Centers for Disease Control and Prevention (CDC)

11. Centers for Disease Control and Prevention (CDC)

12. Centers for Disease Control and Prevention (CDC)

13. Public Access to Rescue Saves Lives

14. Rescue Therapies AED 66% effective in perfect use
Complicated instructions

15. Public health crisis?
100% effective antidote?
No checking for puddles?
No shaving?

16. Public Naloxone Access Underused
“The AMA has been a longtime supporter of increasing the availability of Naloxone for patients, first responders and bystanders who can help save lives and has provided resources to bolster legislative efforts to increase access to this medication in several states.”
ASAM Board of Directors
April 2010
“Naloxone has been proven to be an effective, fast-acting, inexpensive and non-addictive opioid antagonist with minimal side effects... Naloxone can be administered quickly and effectively by trained professional and lay individuals who observe the initial signs of an opioid overdose reaction.”
“APhA supports the pharmacist’s role in selecting appropriate therapy and dosing and initiating and providing education about the proper use of opioid reversal agents to prevent opioid-related deaths due to overdose”

17. Fatal Opioid Overdose Rates in Communities with Naloxone Programs
Naloxone Trained
per 100K
Opioid Overdose Death Rate
BMJ. 2013 Jan 30;346:f174. doi: /bmj.f174.
Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: interrupted time series analysis.
Walley AY1, Xuan Z, Hackman HH, Quinn E, Doe-Simkins M, Sorensen-Alawad A, Ruiz S, Ozonoff A.
Author information
Abstract
OBJECTIVE:
To evaluate the impact of state supported overdose education and nasal naloxone distribution (OEND) programs on rates of opioid related death from overdose and acute care utilization in Massachusetts.
DESIGN:
Interrupted time series analysis of opioid related overdose death and acute care utilization rates from 2002 to 2009 comparing community-year strata with high and low rates of OEND implementation to those with no implementation.
SETTING:
19 Massachusetts communities (geographically distinct cities and towns) with at least five fatal opioid overdoses in each of the years 2004 to 2006.
PARTICIPANTS:
OEND was implemented among opioid users at risk for overdose, social service agency staff, family, and friends of opioid users.
INTERVENTION:
OEND programs equipped people at risk for overdose and bystanders with nasal naloxone rescue kits and trained them how to prevent, recognize, and respond to an overdose by engaging emergency medical services, providing rescue breathing, and delivering naloxone.
MAIN OUTCOME MEASURES:
Adjusted rate ratios for annual deaths related to opioid overdose and utilization of acute care hospitals.
RESULTS:
Among these communities, OEND programs trained 2912 potential bystanders who reported 327 rescues. Both community-year strata with enrollments per 100,000 population (adjusted rate ratio 0.73, 95% confidence interval 0.57 to 0.91) and community-year strata with greater than 100 enrollments per 100,000 population (0.54, 0.39 to 0.76) had significantly reduced adjusted rate ratios compared with communities with no implementation. Differences in rates of acute care hospital utilization were not significant.
CONCLUSIONS:
Opioid overdose death rates were reduced in communities where OEND was implemented. This study provides observational evidence that by training potential bystanders to prevent, recognize, and respond to opioid overdoses, OEND is an effective intervention.
PMID: 
Overdose Education and Nasal Naloxone Distribution (OEND)
Walley AY, et al. BMJ Jan 30;346:f174.
Alexander Y. Walley, MD, MSc, Overdose Prevention Interventions

18. Fatal Opioid Overdose Rates in Communities with Naloxone Programs
Naloxone Trained
per 100K
Opioid Overdose Death Rate
27%
Reductions
BMJ. 2013 Jan 30;346:f174. doi: /bmj.f174.
Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: interrupted time series analysis.
Walley AY1, Xuan Z, Hackman HH, Quinn E, Doe-Simkins M, Sorensen-Alawad A, Ruiz S, Ozonoff A.
Author information
Abstract
OBJECTIVE:
To evaluate the impact of state supported overdose education and nasal naloxone distribution (OEND) programs on rates of opioid related death from overdose and acute care utilization in Massachusetts.
DESIGN:
Interrupted time series analysis of opioid related overdose death and acute care utilization rates from 2002 to 2009 comparing community-year strata with high and low rates of OEND implementation to those with no implementation.
SETTING:
19 Massachusetts communities (geographically distinct cities and towns) with at least five fatal opioid overdoses in each of the years 2004 to 2006.
PARTICIPANTS:
OEND was implemented among opioid users at risk for overdose, social service agency staff, family, and friends of opioid users.
INTERVENTION:
OEND programs equipped people at risk for overdose and bystanders with nasal naloxone rescue kits and trained them how to prevent, recognize, and respond to an overdose by engaging emergency medical services, providing rescue breathing, and delivering naloxone.
MAIN OUTCOME MEASURES:
Adjusted rate ratios for annual deaths related to opioid overdose and utilization of acute care hospitals.
RESULTS:
Among these communities, OEND programs trained 2912 potential bystanders who reported 327 rescues. Both community-year strata with enrollments per 100,000 population (adjusted rate ratio 0.73, 95% confidence interval 0.57 to 0.91) and community-year strata with greater than 100 enrollments per 100,000 population (0.54, 0.39 to 0.76) had significantly reduced adjusted rate ratios compared with communities with no implementation. Differences in rates of acute care hospital utilization were not significant.
CONCLUSIONS:
Opioid overdose death rates were reduced in communities where OEND was implemented. This study provides observational evidence that by training potential bystanders to prevent, recognize, and respond to opioid overdoses, OEND is an effective intervention.
PMID: 
Overdose Education and Nasal Naloxone Distribution (OEND)
Walley AY, et al. BMJ Jan 30;346:f174.
Alexander Y. Walley, MD, MSc, Overdose Prevention Interventions

19. Fatal Opioid Overdose Rates in Communities with Naloxone Programs
Naloxone Trained
per 100K
Opioid Overdose Death Rate
27%
46%
Reductions
BMJ. 2013 Jan 30;346:f174. doi: /bmj.f174.
Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: interrupted time series analysis.
Walley AY1, Xuan Z, Hackman HH, Quinn E, Doe-Simkins M, Sorensen-Alawad A, Ruiz S, Ozonoff A.
Author information
Abstract
OBJECTIVE:
To evaluate the impact of state supported overdose education and nasal naloxone distribution (OEND) programs on rates of opioid related death from overdose and acute care utilization in Massachusetts.
DESIGN:
Interrupted time series analysis of opioid related overdose death and acute care utilization rates from 2002 to 2009 comparing community-year strata with high and low rates of OEND implementation to those with no implementation.
SETTING:
19 Massachusetts communities (geographically distinct cities and towns) with at least five fatal opioid overdoses in each of the years 2004 to 2006.
PARTICIPANTS:
OEND was implemented among opioid users at risk for overdose, social service agency staff, family, and friends of opioid users.
INTERVENTION:
OEND programs equipped people at risk for overdose and bystanders with nasal naloxone rescue kits and trained them how to prevent, recognize, and respond to an overdose by engaging emergency medical services, providing rescue breathing, and delivering naloxone.
MAIN OUTCOME MEASURES:
Adjusted rate ratios for annual deaths related to opioid overdose and utilization of acute care hospitals.
RESULTS:
Among these communities, OEND programs trained 2912 potential bystanders who reported 327 rescues. Both community-year strata with enrollments per 100,000 population (adjusted rate ratio 0.73, 95% confidence interval 0.57 to 0.91) and community-year strata with greater than 100 enrollments per 100,000 population (0.54, 0.39 to 0.76) had significantly reduced adjusted rate ratios compared with communities with no implementation. Differences in rates of acute care hospital utilization were not significant.
CONCLUSIONS:
Opioid overdose death rates were reduced in communities where OEND was implemented. This study provides observational evidence that by training potential bystanders to prevent, recognize, and respond to opioid overdoses, OEND is an effective intervention.
PMID: 
Overdose Education and Nasal Naloxone Distribution (OEND)
Walley AY, et al. BMJ Jan 30;346:f174.
Alexander Y. Walley, MD, MSc, Overdose Prevention Interventions

20. Increasing Community Access
2013 Wisconsin ACT 200- Opioid Overdose and Opioid Antagonists
Allowed prescribers to write Naloxone prescriptions OR standing pharmacy order FOR:
Persons at risk for overdose
Person in position to assist someone at risk for drug overdose (family, friends)
Any person who prescribes or administers an opioid antagonist to another, whom the person reasonably believes to be undergoing an opioid-related drug overdose, is immune from civil or criminal liability
First responder naloxone carrying and administration (Police, Fire Fighter, EMT)

21. Increasing Community Access
2015 Wisconsin ACT 115- Dispensing Opioid Antagonists
Allows prescriber to authorize pharmacists to dispense opioid antagonists to patients under a standing order
Dr Jonathan Meiman- Standing Order
(Chief medical officer of the department of behavior health)
First responder naloxone carrying and administration (Police, Fire Fighter, EMT)

22. State Wide Standing Naloxone Order
All pharmacies across state can dispense naloxone without a direct prescriber to patient prescription
1 hour of training
Must provide educational materials
Must record dispensing
First responder naloxone carrying and administration (Police, Fire Fighter, EMT)

23. Who is a Candidate for Naloxone?
At risk of overdose, including those with:
Higher-dose (>50 mg morphine equivalent/day) opioid prescription
Receiving any opioid prescription for pain plus:
Rotated from one opioid to another because of possible incomplete cross tolerance
Smoking, COPD, emphysema, asthma, sleep apnea, respiratory infection, or other respiratory illness or potential obstruction
Renal dysfunction, hepatic disease, cardiac illness, HIV/AIDS
Known or suspected concurrent alcohol use
Concurrent benzodiazepine or other sedative prescription
Concurrent antidepressant prescription
Reproduced from Jeffrey Bratberg - Naloxone Rescue Kits: Prescribing, Stocking, Filling and Billing

24. Common Risks for Opioid Overdose
Risk Factors
Mixing substances
Abstinence - low tolerance
Using alone
Unknown source
Chronic medical disease
Long acting opioids last longer
Many of the risks for opioid overdose are well established, which can be helpful in educating patients. But we need to ask patients and learn their history
The risk of overdose increases as the dose of prescription opioids increases. For our patients who use heroin, unexpected changes in purity which occur all the time can lead to overdose.
Mixing psychoactive substance and polypharmacy, including alcohol, stimulants, marijuana, prescribed and non-prescribed medications are major contributors to overdose risk. While opioids are typically involved in ¾ of overdose deaths, at least one other substance is typically involved in addition to the opioid. Psychoactive medications of particular concern include controlled medications like benzodiazepines, barbiturates, and stimulants, but also medications that are relatively benign when used on their own, but have synergistically sedating effects when used with opioids, like clonidine, promethazine and gabapentin .
People who are socially isolated, whether they are using illicit or prescribed opioids, are at increased risk of dying form overdose, because if and when they overdose there is no one there to rescue them. Educate patients that if they are going to use opioids, someone else should be around if they use too much.
Chronic medical illness, particularly lung, liver, and kidney compromise, increase risk of overdose because these are the organs that metabolize substances and are responsible for oxygenation.
Patients who have had a prior non-fatal overdose are at increased risk of having a fatal overdose
Patients with a previous addiction history are at risk for relapse and are therefore are at increased risk of overdose.
Periods of abstinence should trigger us to educate our patients about overdose. Particularly concerning are patients released form incarceration and patients leaving detox. We also need to think about patients in recovery and abstinent from opioids and educate them about their increased risk if they relapse.

25. High Risk- Overdose History
Have you ever overdosed?
Have you ever witnessed an overdose?
What do you plan to do if you see an overdose?
Are you interested in having preventative resources?
Reproduced from Jeffrey Bratberg - Naloxone Rescue Kits: Prescribing, Stocking, Filling and Billing

26. Naloxone Prescription
Route
Formulation
Intramuscular
0.4 mg/ml vial
Auto injector
Evzio auto injector
Intranasal solution
2mg/2ml OR
4 mg/0.1 ml

27. Naloxone Rescue Identify overdose Call 911 Provide rescue breathing
Give naloxone
Place in Recovery position
Wait until help arrives

28. Naloxone Counseling Onset- 3-5 minutes Duration- 30-90 minutes
After Naloxone is given, rescue breath for 3-5 minutes
Duration minutes
Patients may re- experience overdose (especially long acting)
Patients may experience withdrawal and want to take more opioids
Do not use more opioids

29. Naloxone Counseling
Prescribetoprevent.org

30. Naloxone Counseling

31. Naloxone Pharmacies
Dhs.wisconsin.gov/opioids

32. Challenges Reimbursement of naloxone Medicaid covers patient of record
Private health care insurers – inconsistent
Undetermined coverage for family or friends

33. Costs (4/25/2018) Pharmacy Intranasal 2-pack Walmart 4 mg/0.1 ml $37
Froedtert
Hospital
$76
CVS
$95
Walgreens
$135
Roundy's
$150

34. Costs (4/25/2018)
Goodrx.com
2 mg/2ml Prefilled syringe

35. Aids Resource Center of Wisconsin

36. Questions?