Chin Hwa (Gina) Dahlem PhD, FNP-C, FAANPginayi@med.umich.edu

Objectives

qDescribe the current opioid epidemiology, legislation, and community naloxone programs

qIdentify the core components of opioid overdose prevention education

qDescribe the different formulations and pharmacokinetics of naloxone

qDiscuss how to incorporate co-prescribing naloxone into routine clinical practice

Acknowledgement• Materials adapted from SAMHSA Opioid

Overdose Toolkit, Harm Reduction Coalition, and University of Michigan School of Nursing in partnership with Washtenaw County Sheriff’s Office Home of New Vision, and Community Mental Health Partnership of Southeast Michigan.

Alarming Statistics

• Provisional opioid-related DEATHS in 2018: • 47, 092

CDC. National Center for Health Statistics. https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htmAccessed on September 27th, 2019

https://mi-suddr.com/opioids/ accessed on Sept 27th, 2019

Death Rate = 27.8/100K

14

11 Million2016

CDC Evidence-Based Strategies for Opioid Overdose Prevention

Naloxone Medication-Assisted Treatment (MAT)

Other

Targeted distribution Eliminate PA requirements

Syringe services programs

Distribution in treatment centers

Initiate MAT in criminal justice settings and upon release

911 Good Samaritan Laws

Distribution in criminal justice settings

Initiate MAT in EDs Screening for fentanyl in routine clinical toxicology testing

Academic detailing (CDC, 2018)

Slide adapted & used with permission: Walley, A.

Naloxone Prescriptions

Coffin PO, Sullivan SD. Cost-effectiveness of distributing naloxone to heroin users for lay overdose reversal. Annals Internal Medicine. 2013;158(1):1-9.Coffin PO et al. Nonrandomized intervention study of naloxone coprescription for primary care patients receiving long-term opioid therapy for pain. Annals Internal Medicine. 2016; 165(4): 245-52.Behar, E. et al. Acceptability and feasibility of naloxone prescribing in primary care settings: a systematic review. PreventiveMedicine. 2018; 114: 79-87.

• Cost Effective:• 1 death prevented for every 227 naloxone kits

distributed• $438/per quality-adjusted life-year gained

• 47% fewer opioid-related ED visits compared to those who did not receive naloxone prescription for patients on long-term opioid pain therapy

• Patients and PCPs find offer of naloxone prescription acceptable and feasible

The person who receives naloxone will react violently when the medication is administered and his/her overdose is reversed.

People experience withdrawal symptoms which makes them feel lousy. In majority of overdoses, people are often disoriented and shocked when waking up to people they don’t know.

Myth Fact

Myths and Facts

Using naloxone will delay entry into drug treatment and encourage riskier drug use.

• Studies show reduction or no change in drug use (Seal et al, 2005; Doe-Simkins et al, 2014; Wagner et al., 2010)

• Naloxone does not enable – it only enables OD victim to breathe.

• Dead people don’t recover.

Myth Fact

Myths and Facts

It is really hard to prevent a person from dying of an opioid overdose since people usually use drugs in private.

The majority of overdoses occur in the presence of others (Strang et al., 2000)

Myth Fact

Myths and Facts

Michigan LegislationHouse Bill 5406; Public Act 313 of 2014

A person that administers an opioid antagonist to an individual who he or she believes is suffering an opioid-related overdose and that acts in good faith and with reasonable care isimmune from criminal prosecution or sanction under any professional licensing act for that act.

Good Samaritan Law

• House Bill 5649, 5650; Public Act 307 of 2016• Gives overdosing drug user limited criminal

immunity (from possession charges and illicit use of controlled substances) when seeking treatment for him / herself or summoning medical assistance for someone else

• Does not apply if you have a warrant for your arrest, possesses more drug than personal use.

Michigan Legislation

• Allows naloxone to be prescribed to friends and families • Requires emergency medical personnel to carry

naloxone and be trained to administer• Allows pharmacists to dispense naloxone with standing

order • Gives school boards the option to obtain a prescription

for naloxone to be administered by a school nurse or other trained employee in case of a student overdose.

Onset, Potency, Duration of OpioidsOral (potency compared to Morphine)

Onset Duration

Morphine 15-60min 4-6 hrs

Hydrocodone 10-30min 4-6 hrs

Heroin (2x) Intense euphoria 45sec-several mins; peak effect 1-2hrs

3-5 hrs

Methadone 30-60mins 22-48 hrs

Fentanyl (100x) 5-15mins 1-2 hrs

Carfentanil (10,000x) In moose, elk: 2-20mins

But what is DEADLY?

Fentanyl Forms

Fentanyl in PowderFentanyl Crystals and Pills

• Can be found in powder, pill, patch, solutions, and rocks

• Mostly found mixed with or sold as heroin•

Fentanyl Precautions

• Cases of fentanyl overdoses among first responders and community laypersons are RARE

• This should NOT delay our responsibility to respond to overdoses or cause fear

• 1000s of lives have been saved without increasing reports of fentanyl overdoses among first responders

American College Medical Toxicology and American Academy of Clinical Toxicology Position Statement• 2017 Position Statement: Prevention Occupational

Fentanyl and Fentanyl Analog Exposure to Emergency Responders

• “We have not seen reports of emergency responders developing signs or symptoms consistent with opioid toxicity from incidental contact with opioids. Incidental dermal absorption is unlikely to cause opioid toxicity”

• “At the highest airborne concentration encountered by workers, an unprotected individual would require nearly 200 minutes of exposure to reach a dose of 100mcg of fentanyl.”

Fentanyl Exposure• For POSSIBLE EXPOSURES:

• Prevent further contamination and notify other first responders and dispatch

• Do NOT touch your eyes, mouth, nose, or any skin after touching any potentially contaminated surface.

• Wash skin thoroughly with cool water, and soap if available

• Do NOT use hand sanitizers as they may enhance absorption

Who is at risk?

USER

Risk Factors to Overdose• Prior history of overdose (Darke et al., 2007; Kinner et al, 2012)

• Tolerance changes• 1-4weeks post-discharge from jail, prison, and/or

detox (Ranapurwala et al., 2018; Maughan & Becker, 2019)

• Potency of opioid• Daily opioid dosages higher than 50 MME (Dunn et al, 2010;

Bohnert et al, 2011)

• Using extended-release and long-acting opioids (Miller et al., 2015)

• Street drugs are unpredictable. Higher purity, greater risk.

Identifying At-Risk PatientsChronic Pain Patient Survey:• nearly 1 in 5 had experienced an

overdose • >half engaged in high-risk

behaviors• only 3% reported having a

naloxone prescription or being trained to deliver naloxone

• nearly 40% had witnessed an overdose.

Dunn KE , et al. Opioid Overdose History, Risk Behaviors, and Knowledge in Patients Taking Prescribed Opioids for Chronic Pain. Pain Medicine. 2017; 18 (8): 1505–1515.

Risk Factors to Overdose• Mixing opioids with other drugs (Park et al., 2016; Gladden et al.

2019)

• Alcohol• Benzodiazepines, anti-anxiety• Stimulants: cocaine, methamphetamine

• History of medical conditions (Brady et al., 2017; Zedler et al., 2014; Nadpara et al., 2018)

• Mental health illness: bipolar, schizophrenia, depression

• Respiratory (COPD/asthma, sleep apnea)• Cardiac, renal, HIV/AIDS

How Do Opioids Affect Breathing?

Lung

muscles

relax

Breathing Slows

Lack of oxygen to brain

Unres-ponsive

Uncon-scious

Breath-ing

Stops

Heart Stops Death

Breathing slows down until it stops. Occur seconds to minutes to hours after drug use.

• Opioids bind to opioid receptors (mu) in the brain and in the spinal cord• When too many opioids are bound to the receptors in the brain, your:

Really High vs Overdose SignsREALLY HIGH OVERDOSE

Nodding off but responsive to stimulation

Unresponsive to pain

Breathing 8 or more times/minute Blue to purple or grayish lips and fingertips

Sleepy looking Very infrequent or no breathing (<8breaths/min)

Speech is slowed/slurred Deep snoring or gurgling (death rattle)

Very small (pinpoint) pupils

Overdose and Naloxone• Used by medical professionals since 1971• Opioid antagonist: Blocks the receptor and

prevents the body from experiencing the effects of opioid

Naloxone Formulations

IN:Prefilled requires atomizer

IM: requires needle syringe

IM: Auto-Injector

IN:Nasal Spray

What is Naloxone?

• Only reverses opioid overdoses• No effect if you do NOT have opioids in

your body• No abuse potential

• Can’t get high, or modified for recreational use• Not a scheduled drug• Pregnancy Category C

• Recommended for suspected OD emergencies• Shelf life = 18-24 months

What is Naloxone?• Acts quickly, 2-5 mins, often in <3mins

• Works for only 30-120 minutes• Depending on amount, type of drug used, and type of

naloxone formulation

• Overdose symptoms may RETURN

• May be repeated every 2-3 minutes

Naloxone nasal spray (Narcan®)4mg/0.1mL

Injectable (IM)naloxone

Autoinjector naloxone (Evzio®)0.4mg/0.4mL or 2mg/0.4 mL

Injectable (IN) Pre-filled syringe

Rx and Quantity

#1 two-pack of two 4mg/0.1mL intranasal device

#2 single-use 1 mL vials PLUS #2 3 mL syringe w/23-25 gauge 1-1.5 inch IM needles

#1 two-pack of two 0.4mg/0.4 mL prefilled auto-injector devices

#2 2 mL luer-Jet Luer-Lock needleless syringe plus #2 mucosal atomizer devices (MAD-300)

Sig. for suspected overdose

Spray into onenostril. Repeat with second device into other nostril after 2-3 minutes if no or minimal response

Inject 1 mL in shoulder or thigh. Repeat in 2-3 minutes if no or minimal response

Inject into outer thigh as directed by voice-prompt. Hold for 5 seconds. Repeat with 2nd

device if no or minimal response

Spray 1 ML (1/2 of syringe) into each nostril. Repeat after 2-3 minutes if no or minimal response

Duration About 120 minutes

30-90 mins 30-90 mins 30-90 mins

StorageProtect from light

Room temp59-77F

Room temp68--77F

Room temp 59-77F

Room temp59-77F

Cost Approx

$169 1 syringe $40 1 atomizer $5

1 vial $13-$40 $4600

Naloxone: Side Effects

Withdrawal symptoms illustrations by Corneail, D. (2017).

Opioid Overdose Response

www.overdoseaction.org

Arouse the person-3 “S” : shout, shake, sternal rub

Check for signs of opioid overdoseTelephone 911Intranasal/Intramuscular NaloxoneO: Oxygen

-2 rescue breath, and/or CPR if you know how, or follow dispatch instructions

N: Naloxone again in 2-3 mins-Recovery position if you must leave or person vomits-Position of comfort if breathing again-Stay with the person till help arrives

Narcan Nasal Spray Instructions

Peel open Place the tip in the person’s nostril

Push on the plunger to administer.

NO TEST SPRAYIS NEEDED

Narcan nasal spray illustrations by Song, W. 2017.

What NOT to do during an Overdose

• Do not put the victim in a bath of cold/ice water• Wastes time, slows the heart down and increase risk for

arrhythmia and drowning• Do not induce vomiting. • Do not give the victim something to drink.

• Could choke, aspirate – more difficult to breathe• Do not put ice down the victim’s pants• Do not slap too hard, kick them in the testicles, burn the

bottom of their feet• Can cause long term damage

• Do not inject (saltwater, cocaine, milk) the victim with anything

Talking Tips

Strategies to Incorporate Co-Prescribing

Into Your Clinical Practice

CDC RecommendationsConsider co-prescribing naloxone to:

• History of overdose• History of SUD• Concurrently using benzos• Opioid dosages higher

than 50 MME/dayAnyone otherwise at risk of experiencing or witnessing an opioid overdose* (expert opinion)

Karnath, L. (2018). MOON Study and Prevent-Protecthttp://prevent-protect.org/community-resources-1/posters/

50 MME/day 90 MME/day

50 mg hydrocodone = 10 tabs of hydrocodone/acetaminophen 5/300)

90 mg of hydrocodone = 9tabs of hydrocodone/acetaminophen 10/325

33 mg oxycodone = ~2 tabs of oxycodone SR 15mg

60 mg of oxycodone = ~ 2 tabs of oxycodone SR 30mg

Naloxone Screening??• None exist• Screening tools for substance use disorders

• https://www.drugabuse.gov/nidamed-medical-health-professionals/screening-tools-resources/chart-screening-tools

• One item screener in primary care• “How many times in the past year have you used an

illegal drug or used a prescription medication for nonmedical reasons?” (Smith et al, 2010)

• Consider: Are you concerned about a family and friend who is using opioids?

Devries, J et al., 2016

Talking TipsThe word overdose can have negative connotations. People who use prescription opioids may not see themselves as being at risk of overdose (Coffin et al., 2016)

Instead, use:• Accidental overdose• Bad reaction• Opioid safety

Conversation Starters• I care about your

safety. • All medications have

side effects and one harmful side effect of taking too many opioids is that it will slow or even stop your breathing.

Conversation StartersJust like we prescribe an epi-pen to someone who has an allergy, we prescribe naloxone to someone who may have an accidental overdose or bad reaction to the opioid medication.Have you heard of naloxone? Naloxone is a lifesaver, like having a fire extinguisher. Hopefully, you will not need it, but it is important to have just in case you do need it.

Conversation Starters“It is also important to share with your family and friends where you keep naloxone and how to administer it.”

“You can even use naloxone to give it someone else as there are laws to protect you in Michigan to release you from any liability.“

Reducing Risks to Overdose

• Do not mix with other drugs especially alcohol, benzos, and anything that makes you sleepy

• Store medication out of reach of children and pets

• Dispose unused medications properly

Reducing Risks to Overdose

• Go slow, never use alone, and carry naloxone

• Alternate injection sites• Reduce substance

amounts• Be aware of tolerance

changes• Train friends to call for

help and give naloxone

Patient Education Content• Brief 5-10 min training sufficient• Brochures/Videos

• How to respond• How to use naloxone

• Videos/Online Training:resources OVERDOSE ACTION NALOXONE TRAINING: overdoseaction.org For opioid overdose naloxone training

TREATMENT CENTERS HOME OF NEW VISION homeofnewvision.org 734.975.1602 - Even Month Birthdays

DAWN FARMS dawnfarm.org 734.669.8265 - Odd Month Birthdays

If you live in: Livingston County, MI - 517.546.4126 Monroe County, MI - 734.243.7340 Lenawee County, MI - 517.263.8905

HARM REDUCTION AND SYRINGE ACCESS UNIFIED miunified.org 734.961.1082

Opioid Overdose Deaths are Preventable.

If you suspect someone is experiencing an opioid overdose,

have your naloxone accessible and take immediate A-C-T-I-O-NFunding was provided by Michigan Institute for Clinical & Health

Research UL1TR000433, Michigan Department of Health and Human Services and Community Mental Health Partnership of Southeast

Michigan

© 2017 The Regents of the University of Michigan

All rights reserved.

opioid safety & naloxoneTAKE A.C.T.I.O.N. AND SAVE A LIFEwww.overdoseaction.org

WHAT ARE OPIOIDS?Opioids are a class of drugs that reduce pain and promote feelings of pleasure and relaxation. Taking too many opioids slows your breathing which leads to lack of oxygen in your brain, coma, heart stopping, and death. This process can be fast, so time is critical to saving a life.

Common opioids include prescription opioids, heroin, and illicit fentanyl.

WHAT ARE THE SIGNS OF AN OVERDOSE?• Blue lips/fingernails (ashen if darker skin)• Breathing that is infrequent, uneven or

has stopped• Deep snoring or gurgling noises• Unresponsive to pain stimulus• Pinpoint pupils

WHAT IS NALOXONE?• Naloxone (Narcan,® Evzio®) is a drug that

temporarily reverses the dangerous effects of an opioid overdose

• Naloxone can be given every 2-3 minutes, but only works if opioids are in your body

• Works for reversing fentanyl overdoses• A person cannot get high on it or become

addicted to it

EFFECTIVE ONLY FOR 30 TO 120 MINUTES

www.prescribetoprevent.orgwww.overdoseaction.org

naloxoneaccess

Standing Order from State RegisteredPharmacies

michigan.gov/mdhhs and search "naloxone"

Agencies that distribute naloxone for free:hopeandrecovery.org

High Schools & Colleges/Universities:

https://www.narcan.com/partnerships

Kaleo Cares Program:evzio.com/patient/in-chronic-pain/kaleo-cares/

Evzio 2 You Program:evzio.com/patient/in-chronic-pain/evzio2you/

Prescription from a physician, physicianassistant, or nurse practitioner

Limited supply of intranasal narcan sprayavailable for community trainings & individualswho would have financial difficulties when usingthe pharmacy standing order

michigan.gov/documents/PIHPDIRECTOR_97962_7.pdf

How to Access Naloxone:

• Pharmacy Standing Order• http://www.michigan.gov/mdhhs/0,5885,7-

339-71550_2941_4871_79584_80133_80135_80309-426713--,00.html

• Harm Reduction Agencies• PIHP• Community Organizations

Inaugual naloxone training class Washtenaw County Sheriff’s Office, Personal Photo, August 7th, 2015

to save livescarry naloxone

Questions??

www.overdoseaction.org

ReferencesBehar E, Bagnulo R, Coffin PO. Acceptability and feasibility of naloxone prescribing in primary care settings: A systematic review. Prev Med (Baltim). 2018;114:79-87. doi:10.1016/j.ypmed.2018.06.005

Bohnert ASB, Valenstein M, Bair MJ, et al. Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA. 2011;305(13):1315-1321. doi:10.1001/jama.2011.370

Brady JE, Giglio R, Keyes KM, DiMaggio C, Li G. Risk markers for fatal and non-fatal prescription drug overdose: a meta-analysis. Inj Epidemiol. 2017;4(1):24. doi:10.1186/S40621-017-0118-7

CDC. National Center for Health Statistics. https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm Accessed on September 27th, 2019

Centers for Disease Control and Prevention. Evidence-Based Strategies for Preventing Opioid Overdose: What’s Working in the United States. National Center for Injury Prevention and Control, Centers for Disease Control and Prevention, U.S. Departmentof Health and Human Services, 2018. Accessed February 21st, 2019 from http://www. cdc.gov/drugoverdose/pdf/pubs/2018-evidence-based-strategies.pdf

Coffin, P. O., & Sullivan, S. D. (2013). Cost-effectiveness of distributing naloxone to heroin users for lay overdose reversal. Annals of Internal Medicine, 158(1), 1-9. 10.7326/0003-4819-158-1-201301010-00003 [doi]

Coffin, P.O., Behar, E., Rowe, C., Santos, G.M., Coffa, D., Bald, M., et al. (2016). Nonrandomized intervention study of naloxone coprescription for primary care patients receiving long-term opioid therapy for pain. Annals of Internal Medicine, 165(4), 245-52.

Doe-Simkins, M., Quinn, E., Xuan, Z., Sorensen-Alawad, A., Hackman, H., Ozonoff, A., & Walley, A. Y. (2014). Overdose rescues by trained and untrained participants and change in opioid use among substance-using participants in overdose education and naloxone distribution programs: A retrospective cohort study. BMC Public Health, 14, 297-2458-14-297. 10.1186/1471-2458-14-297 [doi]

Darke S, Duflou J, Kaye S. (2007). Comparative toxicology of fatal heroin overdose cases and morphine positive homicide victims. Addiction 102(11): 1793-7.

Devries J, Rafie S, Polston G. Implementing an overdose education and naloxone distribution program in a health system. J Am Pharm Assoc. 2017;57(2):S154-S160. doi:10.1016/j.japh.2017.01.002

ReferencesDunn KE , et al. Opioid Overdose History, Risk Behaviors, and Knowledge in Patients Taking Prescribed Opioids for Chronic Pain. Pain Medicine. 2017; 18 (8): 1505–1515.

Dunn KM, Saunders KW, Rutter CM, et al. Opioid Prescriptions for Chronic Pain and Overdose. Ann Intern Med. 2010;152(2):85. doi:10.7326/0003-4819-152-2-201001190-00006

Gladden RM, O’Donnell J, Mattson CL, Seth P. Changes in Opioid-Involved Overdose Deaths by Opioid Type and Presence of Benzodiazepines, Cocaine, and Methamphetamine - 25 States, July-December 2017 to January-June 2018. MMWR Morb Mortal Wkly Rep. 2019;68(34):737-744. doi:10.15585/mmwr.mm6834a2

Kinner SA, Milloy M-J, Wood E, Qi J, Zhang R, Kerr T. Incidence and risk factors for non-fatal overdose among a cohort of recently incarcerated illicit drug users. Addict Behav. 2012;37(6):691-696. doi:10.1016/j.addbeh.2012.01.019

Maughan BC, Becker EA. Drug-related mortality after discharge from treatment: A record-linkage study of substance abuse clients in Texas, 2006-2012. Drug Alcohol Depend. 2019;204:107473. doi:10.1016/j.drugalcdep.2019.05.011

Michigan Department of Health and Human Services. https://mi-suddr.com/opioids/ Accessed on Sept 27th, 2019

Miller M, Barber CW, Leatherman S, et al. Prescription opioid duration of action and the risk of unintentional overdose among patients receiving opioid therapy. JAMA Intern Med. 2015;175(4):608-615. doi:10.1001/jamainternmed.2014.8071

Nadpara PA, Joyce AR, Murrelle EL, et al. Risk Factors for Serious Prescription Opioid-Induced Respiratory Depression or Overdose: Comparison of Commercially Insured and Veterans Health Affairs Populations. Pain Med. 2018;19(1):79-96. doi:10.1093/pm/pnx038

Park TW, Lin LA, Hosanagar A, Kogowski A, Paige K, Bohnert ASB. Understanding Risk Factors for Opioid Overdose in Clinical Populations to Inform Treatment and Policy. J Addict Med. 2016;10(6):369-381. doi:10.1097/ADM.0000000000000245

ReferencesRanapurwala SI, Shanahan ME, Alexandridis AA, et al. Opioid Overdose Mortality Among Former North Carolina Inmates: 2000-2015. Am J Public Health. 2018;108(9):1207-1213. doi:10.2105/AJPH.2018.304514Seal, K. H., Thawley, R., Gee, L., Bamberger, J., Kral, A. H., Ciccarone, D., . . . Edlin, B. R. (2005). Naloxone distribution and cardiopulmonary resuscitation training for injection drug users to prevent heroin overdose death: A pilot intervention study. Journal of Urban Health : Bulletin of the New York Academy of Medicine, 82(2), 303-311. jti053 [pii]Strang J, McCambridge J, Best D, et al. Loss of tolerance and overdose mortality after inpatient opiate detoxification: follow up study. BMJ. 2003;326(7396):959-960. doi:10.1136/bmj.326.7396.959Smith PC, Schmidt SM, Allensworth-Davies D, Saitz R. A Single-Question Screening Test for Drug Use in Primary Care. Arch Intern Med. 2010;170(13):1155-1160. doi:10.1001/archinternmed.2010.140Wagner, K. D., Valente, T. W., Casanova, M., Partovi, S. M., Mendenhall, B. M., Hundley, J. H., . . . Unger, J. B. (2010). Evaluation of an overdose prevention and response training programme for injection drug users in the skid row area of los angeles, CA. The International Journal on Drug Policy, 21(3), 186-193. 10.1016/j.drugpo.2009.01.003 [doi]Zedler B, Xie L, Wang L, et al. Risk factors for serious prescription opioid-related toxicity or overdose among Veterans Health Administration patients. Pain Med. 2014;15(11):1911-1929. doi:10.1111/pme.12480