The Role of Naloxone in

an Opioid Epidemic
January 20, 2022
Taylor Lager, PharmD
The Role of Naloxone in
an Opioid Epidemic
Kahoot!
https://kahoot.it

Code: 770 3645

 Objectives

1. Recognize the trends of the opioid epidemic in Indiana

2. Define who is at high-risk of accidental opioid overdose and should be offered naloxone

3. Compare and contrast the naloxone products

4. Describe the pharmacist’s role in regards to naloxone

3
Current status of opioid epidemic

4
Opioid Epidemic in the United States

• The CDC reported >100,000 estimated drug overdose deaths in a 12-month period from
May 2020 through April 2021 in the United States (U.S.)
• Synthetic opioids are the leading cause of death which include predominantly illicitly
manufactured fentanyls (IMFs)
• IMFs cases increased ~33% in the Midwest from 2019 to 2020

MMWR Morb Mortal Wkly Rep. 2021 5

Kahoot Question #1

6
Opioid State
Summary
Overdose
Prescriptions
deaths per
State per
100,000 100 persons
persons

W. Virginia 42.4 69.3

Ohio 29.6 53.5

Kentucky 23.4 79.5

Michigan 20.8 62.7

Indiana 17.5 65.8

Illinois 17.0 45.2

National Institute on Drug Abuse. 2020 7

Opioid Epidemic in Indiana
● There was a 41%
increase in fatal drug
overdoses from 2019 to
2020
● Naloxone
administrations across
the state rose 66% for
the same time period

IN.gov website. 2021 8

Indiana
Opioid
Statistics
Recorded 1,875
deaths in 2020

Estimated 1,007
deaths in 2021

Marion County
2020: 510 deaths
2021: 274 deaths

IN.gov website. 2021 9

Who is at risk of accidental opioid overdose and should

be offered naloxone

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CDC Guidance on Prescribing Opioids for Chronic Pain

11
Criteria for high-risk opioid overdose

CDC guidance states that clinicians should offer naloxone when opioid overdose
factors are present.

Factors include:
• History of overdose

• History of substance use disorder

• Higher opioid doses (≥50 morphine milliequivalents/day)

• Concurrent benzodiazepine (BZD) use

MMWR Recomm Rep. 2016 12

Signs & Symptoms of an Opioid Overdose
Miosis Cyanosis Clammy Skin Flushing

Respiratory Depression Bradycardia Nausea and/or Vomiting Unable to awake upon sternal rub

Lexi-Tox. 2021 13
Kahoot Questions #2 - 3

14
Overview of naloxone products

15
Naloxone

Receptor Image. 2018 16

Naloxone Formulations

IM Injectable Naloxone generics, ZIMHITM

Intranasal Narcan®, KloxxadoTM

Auto-Injector Evzio® - removed from market

Lexi-Drugs. 2021 17
Injectable Naloxone - Vials
Available as: naloxone 0.4 mg/mL (1 mL, 10 mL vials)

Adult dosing for opioid overdose

• IM: 0.4 to 2 mg (repeat doses if necessary)
• If no response with a cumulative dose of 10 mg, consider other
causes of respiratory depression

Pediatric dosing for opioid overdose

• IM: 0.1 mg/kg/dose (repeat doses if necessary)
• Max: 2 mg/dose

Sites for IM injection: thighs, deltoid, upper/outer quadrant of glutes

Lexi-Drugs. 2021 18
Naloxone images. https://www.webmd.com/drugs/2/drug-4082-9190/naloxone-injection/naloxone-injection/details
Injectable Naloxone - Prefilled Syringes
Available as: naloxone 2 mg/2 mL, ZIMHITM 5 mg/0.5 mL

Adult dosing for opioid overdose

• IM: 0.4 to 2 mg (repeat doses if necessary)
• If no response with a cumulative dose of 10 mg, consider other
causes of respiratory depression

Pediatric dosing for opioid overdose

• IM: 0.1 mg/kg/dose (repeat doses if necessary)
• Max: 2 mg/dose

Sites for IM injection: thighs, deltoid, upper/outer quadrant of glutes

Lexi-Drugs. 2021 19
Naloxone images. https://www.webmd.com/drugs/2/drug-4082-9190/naloxone-injection/naloxone-injection/details
Injectable Naloxone – Prefilled Syringes
ZIMHITM 5 mg/0.5 mL - FDA Approved October 2021

• Product to market 1st quarter of 2022

• Intended to be given by those 12 years and older

• Inject into the anterolateral thigh

• If administering to pediatric patients under the age of 1, pinch
the thigh muscle when deploying

ZIMHI Package Insert. 2021 20

ZIMHI image. Zimhi.com
Injectable Naloxone – Improvised nasal naloxone device (INND)
Can also convert to intranasal administration
• Not approved by FDA
How to assemble:
• Requires assembly 1) Remove the yellow caps off the syringe.
2) Remove the red cap off from naloxone.
3) Screw nasal atomizer onto the tip of the
syringe barrel.
4) Screw naloxone into the barrel of the
syringe.
5) Once device is constructed, administer by
spraying half (1 mL) of naloxone into one
nostril and then other half (1 mL) into the
other nostril of the patient.

OverdoseLifeline. 2020 21
INND image. Harvard Health Blog.
Injectable Naloxone – Improvised nasal naloxone device (INND)
Can also convert to intranasal administration
• Not approved by FDA
• Requires assembly
A 2015 study from Edwards ET and colleagues
found:
● In a mannequin accidental opioid overdose
simulation, 0% of their 42 participants were
able to correctly use an INND device if only
provided an instructional sheet.
● After 2 coaching and counseling sessions,
only 57% were able to correctly perform each
step to assemble and give the INND

Edwards ET, et al. 2015 22

INND image. Harvard Health Blog.
Intranasal Naloxone
Available as: Narcan® (4 mg/0.1 mL), KloxxadoTM (8 mg/0.1 mL)
Dosing for opioid overdose in adults and pediatrics
• 4 or 8 mg (contents of 1 spray) as a single dose into the nostril
• Repeat every 2-3 minutes in alternating nostrils
• Do NOT prime these devices
Narcan nasal spray updates - generic underway!

Lexi-Drugs. 2021
Generics Bulletin. 2021 23
Intranasal Generic Naloxone

● Teva just released generic naloxone!

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Intranasal Naloxone
KloxxadoTM
• FDA approved April 30, 2021

• Now available to order

• Currently the highest dose of naloxone product available

• Manufacturer references that 34% of opioid overdose reversals
with naloxone required at least a second administration of
therapy to fully reverse an accidental overdose

Kloxxado website. 2021 25

Evzio® Update
2020
• Kaléo pharmaceutical company discontinued Evzio® and
it’s respective generic naloxone auto-injector.
• According corporate communications (C. F. Durham,
electronic communication, December 28, 2021) product
is no longer manufactured and last known batch expired
September 2021.

Evzio Image. 2019 26

Onset of Action for Naloxone Route of Administrations

IV IM, SubQ Nasal spray

~ 2 minutes 2 to 5 minutes ~8 to 12 minutes

Lexi-Drugs. 2021 27
Product Storage Requirements

Injectable NarcanTM KloxxadoTM

solutions nasal spray nasal spray

Storage: 68°- 77° F Storage: 59° - 77° F Storage: 68°- 77° F

Excursions: 39° - 104° F Excursions: 41°- 104°F

Lexi-Drugs. 2021 28
Narcan Package Insert. 2020
Naloxone Price Comparisons*
Pre-filled Generic
NarcanTM KloxxadoTM
Vials generic naloxone
nasal spray nasal spray
syringes nasal spray

0.4 4 mg/10 2 mg/2 mL 4 mg/0.1 mL 8 mg/0.1 mL 4 mg/0.1 mL

mg/mL mL (per 1 mL)
(per 1 (per 1 Two-pack: Two-pack: Teva’s generic for
mL) mL) $18.81 $150 $150 two-pack:
to $142.50
$5.27 $14.19 $19.80
to to Sandoz generic
$23.72 $14.95 for two-pack:
$140.63

* All costs shown are average wholesale pricing (AWP) Lexi-Drugs. 2021 29
Micromedex Red Book. 2021
Kahoot Questions #4 - 6

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Pharmacist’s Role with Naloxone

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Naloxone Access Laws and Pharmacist Distribution in the U.S.

• All 50 states enable

pharmacists to distribute
naloxone without a
patient-specific prescription

• NarcanTM manufacturer
website updates this map with
state laws

Naloxone laws. 2021 32

Impact of state laws that authorize pharmacists to prescribe naloxone

Xu J, Mukherjee S. 2021 33
State laws that authorize pharmacists to prescribe naloxone

Study Design

• Observational, cross-sectional study

Objective

• Investigate the impact of laws permitting pharmacists to prescribe naloxone in U.S.

retail pharmacies. Primary objective was to determine the number of naloxone
prescriptions dispensed by each state per each calendar quarter.

Study Cohort

• Utilized Symphony PHASTTM Prescription Monthly database

• All naloxone prescriptions dispensed from 2010 to 2018. Captured 1,004,820 Brand
name products and 148,563 generic naloxone products.

Xu J, Mukherjee S. 2021 34
State laws that authorize pharmacists to prescribe naloxone
Results
• Average dispensation of naloxone rose 331 prescriptions per quarter in states that
enacted pharmacist prescriptive authority with naloxone access laws. (p < 0.05)
• This represents a 53% change per state, per quarter.
• It was not until 1 year after the implementation of these laws that marginal
increases were seen with naloxone dispensation.

Discussion
• Authors note another study (Abouk et al.) found naloxone access laws that allow
pharmacists to have full prescriptive authority or dispense naloxone without a
prescription were associated with reductions in fatal overdoses.
• These results indicate that retail pharmacies are an important method of naloxone
distribution.

Conclusions

• Naloxone access laws such as pharmacists have prescriptive authority are helpful to
increase access to naloxone, thus potentially saving lives.

Xu J, Mukherjee S. 2021 35
Indiana Naloxone Access

• Current Law
• Statewide standing order that allows entities to dispense naloxone
IC 16-42-27 Aaron’s law

OptIN website. 2021

Ascension St. Vincent

Current 86th Street resources for naloxone:

• Emergency Department
• Stress Center
• Retail pharmacy

Future 86th Street resources for naloxone:

• Primary Care Center pharmacy

OptIN website. 2021

What can I do?

38
Pharmacist role
Take action!
• Use the CDC criteria to survey your patients if they would qualify for a
co-prescription of naloxone
• Download applications for quick MME calculations
• Sign up for naloxone training
• Carry naloxone with you!

Encourage your patient’s to have naloxone on them and link them to

available resources
Indiana Pharmacists website. 2021
Overdose Lifeline website. 2022
Narcan website. 2021
Last Kahoot!

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Counseling: Do and Don’ts
Initiate conversation
Avoid Use
• Some patients may think it cannot
Risky patients Risky medications
happen to them
“Opioid use disorder”, Substance use disorder
• Use non-judgmental language and abuse
naloxone as a safety measure for
Person who is “clean” Person in long-term
worst case scenario recovery
• Frame that the opioid medications
Overdose, OD Accidental overdose,
themselves are risky; the patient is bad reaction, opioid
not risky emergency

Narcan website. 2021

References
1. O’Donnell J, Tanz LJ, Gladden RM, Davis NI, Bitting J. Trends in and characteristics of drug overdose deaths involving illicitly manufactured fentanyls - United
States, 2019-2020. MMWR Morb Mortal Wkly Rep 2021;70:1740-1746. DOI: http://dx.doi.org/10.15585/mmwr.mm7050e3
2. Opioid summaries by state. National Institute on Drug Abuse website. Updated April 16, 2020. Accessed December 21, 2021.
3. Overdose trends in Indiana during the covid-19 pandemic (preliminary data). IN.gov website. Updated October 2021. Accessed December 21, 2021.
4. Indiana drug overdose dashboard deaths. IN.gov website. Updated November 17, 2021. Accessed December 21, 2021.
5. Dowell D, Maegerich T, Chou R. CDC guideline for prescribing opioids for chronic pain - United States, 2016. MMWR Recomm Rep 2016;65(1).
6. Opioids. Lexi-Tox. Lexicomp. UpToDate, Inc,;2021. Updated December 13, 2021. Accessed December 21, 2021.
7. Receptor image. Practical Recovery website. Updated October 30, 2018. Accessed January 12, 2022.
8. Naloxone. Lexi-Drugs. Lexicomp. UpToDate, Inc,;2021. Updated December 22, 2021. Accessed December 22, 2021.
9. Naloxone images. WebMD website. https://www.webmd.com/drugs/2/drug-4082-9190/naloxone-injection/naloxone-injection/details. Accessed December
21, 2021.
10. ZIMHI. Package insert. Adamis Pharmaceuticals Corporation; 2021.
11. ZIMHI image. Zimhi.com. Accessed December 30, 2021.
12. Intranasal naloxone. OverdoseLifeline website. Updated 2020. Accessed December 30, 2021.
13. INND image. Harvard Health Blog website.
https://www.health.harvard.edu/blog/should-you-carry-the-opioid-overdose-rescue-drug-naloxone-2018050413773. Updated May 4, 2018. Accessed
December 30, 2021.
14. Edwards ET, Edwards ES, Davis E, Mulcare M, Wiklund M, Kelley G. Comparative usability study of a novel auto-injector and an intranasal system for
naloxone delivery. Pain Ther. 2015;4:89-105. DOI: http://10.1007/s40122-015-0035-9
15. Wallace D. Teva and Sandoz go head to head on US Narcan. Generics Bulletin.
https://generics.pharmaintelligence.informa.com/GB151520/Teva-And-Sandoz-Go-Head-To-Head-On-US-Narcan. Updated December 23, 2021. Accessed
January 2, 2022.

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References
16. Help your patients survive an opioid overdose. Kloxxado website for prescribers. https://kloxxado.com/for-prescribers/. Accessed January 2 nd, 2021.
17. Couturier BJ. Evzio image. Virgina Business website. https://www.virginiabusiness.com/article/kaleo-to-produce-generic-version-of-drug-device/. Updated
January 30, 2019. Accessed December 30, 2021.
18. Narcan package insert. Adapt Pharma, Inc.; 2020.
19. IBM Micromedex Red Book. IBM Micromedex. IBM Watson Health; 2021. Accessed January 2, 2021.
20. Naloxone laws. Narcan manufacturer
website.https://www.narcan.com/wp-content/uploads/2021/11/PP-NAR4-US-00562_Availability_USA_Map_Updated_11.10.21-Final.pdf. Updated November 5, 2021.
Accessed January 13, 2022.
21. Xu J, Mukherjee S. State laws that authorize pharmacists to prescribe naloxone are associated with increased naloxone dispensing in retail pharmacies. Drug
Alcohol Depend. 2021;227:109012. DOI: https://doi.org/10.1016/j.drugalcdep.2021.109012
22. Indiana statewide naloxone standing order toolkit for naloxone entities Indiana code. OptIN website.
https://optin.in.gov/files/Indiana-Statewide-Naloxone-Standing-Order-Toolkit.pdf. AccesseDecember 30, 2021.
23. Webinars. Indiana Pharmacist website. https://www.indianapharmacists.org/webinars/. Accessed January 2, 2022.
24. Healthcare professionals pharmacists. Narcan website. https://www.narcan.com/healthcare-professionals/pharmacists/. Accessed January 2, 2022.
25. Overdose Lifeline screenshot. Overdose Lifeline website. https://www.overdoselifeline.org/. Accessed January 2, 2022.

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Questions?