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Fentanyl and Harm Reduction Strategies

William Matthews, Physician AssistantHarm Reduction Coalition

March 29, 2017

Harm Reduction Coalition• Founded in 1993 by needle exchange providers, advocates, and drug users

• Challenge the persistent stigma faced by people who use drugs

• Advocate for policy and public health reform

POLICY & ADVOCACY

TRAINING & CAPACITY

BUILDING

OVERDOSE

PREVENTION & ADVOCACY

NATIONAL & REGIONAL

CONFERENCES

RESOURCES & PUBLICATIONS

The last 30 minutes are reserved for Questions.

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respond when we ask the group what they think.

Webinar Details

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Webinar participants will be able to:

• Recall trends in fentanyl-related deaths;

• Describe pharmacology of fentanyl and its analogues;

• Discuss fentanyl from the drug user perspective;

• Recognize and respond to a fentanyl or opioid overdose

• Identify harm reduction practices that protect against overdose

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What is fentanyl?

• Most powerful opioid routinely used in human medicine• 50 – 100 x painkilling power of morphine • Often used to treat post-surgical and cancer pain

• Rapid onset, short duration

• before 2013 as a recreational drug, was mostly from diversion of legal manufacture.

• Began to appear in large quantities as Illegally Manufactured Fentanyl (IMF) about 2013

• Often mixed with heroin

• Very large increases in overdose deaths in last 2 years appear to be driven by it

NFLIS 2015 annual report

OHIO

• Akron and Canton, Stark County, Ohio, renting mobile morgues

• Increasing deaths from fentanyl with cocaine.

• Increasing appearance of analogues

• Note that graph of Cleveland (Cuyahoga County) includes projected deaths for 2017

• http://www.motherjones.com/politics/2017/03/cleveland-medical-examiner-opioid-fentanyl-

overdose

• https://www.washingtonpost.com/news/to-your-health/wp/2017/03/16/drugs-are-killing-

so-many-in-this-county-that-cold-storage-trailers-are-being-used-as-

morgues/?utm_term=.bd3661acac4b

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Cocaine and fentanyl

• Cocaine-related overdose deaths increased after 2010, despite decreased cocaine use.

• Increase was related to cocaine-related overdose deaths involving opioids, primarily heroin and fentanyl.

American Journal of Public Health: March 2017, Vol. 107, No. 3, pp. 430-432.

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NEW YORK CITY DEPARTMENT OF HEALTH AND MENTAL HYGIENE Increase in drug overdoses deaths and increased presence of

fentanyl in New York City October 17, 2016

Since July 1, 2016, nearly half (47%) of confirmed drug overdose deaths involved fentanyl.

In the previous 10 years, fentanyl was relatively uncommon in overdose deaths, with fewer than 3% of deaths in New York City involving fentanyl.

NY State had a 20.4% increase in OD deaths from 2014 – 15

https://www.cdc.gov/drugoverdose/data/statedeaths.html

13

Fentanyl in NYC

•Wall Street Journal, March 6, 2017:• Fatal opioid ODs increased 60% in 2016

• 2015: 753 (NYCDOHMH)• 2016: ~1,200 (Chief of Detectives Robert Boyce, press conference)

• Increase largely due to fentanyl

• "nearly four times as many opioid-involved overdoses as homicides in 2016.”

https://www.wsj.com/articles/fatal-opioid-overdoses-increased-60-in-new-york-city-in-2016-1488855451

Fentanyl Related²

22%

Heroin Related¹

22%Fentanyl & Heroin Related4

9%

Other Opioid³

47%

Fentanyl Related²

43%

Heroin Related¹

12%

Fentanyl & Heroin Related4

19%

Other Opioid³

26%

¹ No fentanyl; possible other drugs involved² No heroin; possible other drugs involved³ No fentanyl or Heroin; possible other drugs involved4 Possible other drugs involved

¹ NO FENTANYL; POSSIBLE OTHER DRUGS INVOLVED

² NO HEROIN; POSSIBLE OTHER DRUGS INVOLVED

³ NO FENTANYL OR HEROIN; POSSIBLE OTHER DRUGS INVOLVED4 POSSIBLE OTHER DRUGS INVOLVED

FENTANYL

RELATED²

43%

HEROIN

RELATED¹

12%

FENTANYL

& HEROIN

RELATED4

19%

OTHER

OPIOIDS³

26%

SOURCE: ERIE COUNTY MEDICAL EXAMINERS OFFICE, *CLOSED CASES REPORTED THRU 3/1/2017

2015 AND 2016* ERIE COUNTY OPIOID RELATED DEATHS

BY TYPE OF OPIOID

2015N=256

2016*: N=26460 PendingCases as of3/1/2017

FENTANYL

RELATED²59%

HEROIN

RELATED¹9%

FENTANYL

& HEROIN

RELATED4

17%

OTHER

OPIOIDS³16%

Fentanyl in New Hampshire2016 Current Drug Data as of 3/8/2017 OPIATES/OPIOIDS # OF DEATHS

• Fentanyl (no other drugs) 193

• Fentanyl and Other Drugs 121

(excluding heroin)

• Heroin (no other drugs) 3

• Heroin and Other Drugs 21

(excluding fentanyl)

• Heroin and Fentanyl 5

• Other Opioids/analogues 61

• Total Deaths By Opioids 404

• Other drugs 52

• Total Drug Deaths 456

Drug Data Update from NH Medical Examiner's Office 3-8-17

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*CHAT BOX*

Where are you from?

How much fentanyl are you seeing?

Fentanyl pressed into fake pills • Prince’s death: U-47700 also found in his blood.

• Pills first appeared in 2014

• Pill presses have been seized by DEA

• Look like Xanax and other legal medications, very good imitations.

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Fentanyl from China

• China White: in 1950s meant very pure heroin• 1970s became associated with fentanyl-heroin mixtures

• China is now source of most fentanyl and ingredients

• China agrees to curtail manufacture/export

• Two ingredients added to the United Nations' international list of controlled substances on 3/17/17 (ANPP and NPP)

• Impact unclear

• Fentanyl and its analogues do not seem to be an internal drug problem for China

Addict Behav. 2017 May;68:35-38. doi: 10.1016/j.addbeh.2017.01.014

https://en.wikipedia.org/wiki/%CE%91-Methylfentanyl

http://www.bluelight.org/vb/threads/241865-china-white-heroin-or-fentany

http://www.dailymail.co.uk/health/article-4321966/UN-adds-fentanyl-list-controlled-substances.html#ixzz4bb2lN6PE l

• Generally from China

• Shipped through US Postal Service• USPS does not require tracking information

• FedEx and UPS do require tracking info

• Senate bill pending: Synthetics Trafficking and Overdose Prevention (STOP Act)

• USPS would also require tracking information

• China’s bans of “Flakka” (alpha-PVP) in October 2015 was correlated with later reduction in amounts later confiscated in US

http://www.npr.org/2017/03/11/519649096/can-china-ban-on-deadly-opioid-save-lives-in-the-u-s?utm_medium=RSS&utm_campaign=news

Mail Order Drugs

New Psychoactive Substances

• Best know for problems with synthetic cannabinoids (K2, Spice)

• Made in clandestine labs, most commonly in China

• “New” substances are usually derived from old patents that were never marketed

• Most substances were never tested in humans

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Fentanyl analogues

•Very similar structures to fentanyl

•Some were probably introduced to evade law.

Drug Data Update from NH Medical Examiner's Office 3-8-17

Fentanyl Analogues in NH in

2016: U-47700 - 2 deaths

Furanyl fentanyl 3 deaths

Acetyl fentanyl - 39 deaths

Fluoro-fentanyl – 1 death

Acetyl fentanyl and

furanyl fentanyl- 1 death

24

Fentanyl analogues

Analogue Potency compared to morphine in MEQs (Morphine Equivalent Units)

(fentanyl MEQ = 50 – 100)

Acetylfentanyl 15

Furanylfentanyl 20

Acrylfentanyl 50 – 100 (maybe more)

Carfentanyl 10,000 – 100,000

• Analogues may not be detected in standard tests, even in tests for fentanyl

• MEQ = Morphine Equivalent Units, measures painkilling efficacy (usually by ‘Tail flick test”), not how deadly it is

Comparison of acetylfentanyl and furanylfentanyl

Found in USA banned in USA banned in China

• Acetylfentanyl 2013 7/15 10/15

• Furanylfentanyl 12/15 11/16 3/1/17

• DEA furanylfentanyl seizures 2015:• 1st quarter, none• 4th quarter, most common analogue

• Furanylfentanyl appears to have been developed in China as a response to China’s banning acetylfentanyl

• https://qz.com/670685/chinese-drug-dealers-are-outsmarting-the-fda-by-creating-new-opioids/

• https://ndews.umd.edu/resources/dea-emerging-threat-reports

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CarfentanilTranquilizer for very large animals (elk – elephant)

• 10,000 – 100,000 MEQ• This does not mean that it is 10,000 x as lethal as morphine

• Needs special license• Reversed with naltrexone (manufacturer’s recommendation)

• 700 fatalities in states including Ohio, Michigan and Florida

• Very few, if any, ODs from it in NY City or State

• Overdoses can also be reversed with naloxone.

• China is main source, added to list of controlled substances there on 3/1/17.

https://www.wsj.com/articles/u-s-authorities-pressed-china-for-action-on-deadly-opioid-1487327406

Print and Online News Articles Reported Suspected Carfentanil-Related Incidents, as of 9/8/16

Outbreaks of drug problems often come to public attention first via media reports National Drug Early Warning System (NDEWS) Issue 2 ◊September 26, 2016

28

More about Fentanyl

• Not well absorbed through stomach (33%), does not come as a pill• IV, Lozenges, lollypops, Sublingual• Transdermal patches

• Diverted patches• Various methods of extracting drug from the patch• Both new and used patches can be used to get high

• Overdoses can be so rapid that fentanyl only, without the usual breakdown products (metabolites), are found in blood

• Not detected in routine drug tests at treatment centers and primary care

• Anecdotal: Some users seek it unmixed with heroin to avoid drug test detection

Addict Behav. 2017 May;68:35-38. doi: 10.1016/j.addbeh.2017.01.014

29

Users believe they can identify fentanyl

• The rush!

• Appearance: • Heroin is light brown powder (East coast), whiskey

color in solution• Lighter colors more likely to involve fentanyl

• Sometimes:• Taste by finger: sweet; (heroin usually bitter)• Body sensations: pins and needles in neck/head

• Heroin usually warm and fuzzy, longer lasting than fentanyl• Heroin injection produces metallic aftertaste in mouth

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Chest Wall Rigidity (‘Wooden Chest’)

• Known to anesthesiologists

• Associated with large, rapid doses of fentanyl

• Unable to breath due to spasm of chest wall muscles

• Accounts of observed fentanyl overdoses:• Occurs in first minute

• Victims sometimes with ‘air hunger’ gestures; different from respiratory depression.

PI: Dan Ciccarone

Department of Family and Community Medicine, UCSF

Sarah Mars

Jeff Ondocsin

Funding: NIH/NIDA R01:DA037820

Off-white or tan powder

Caramel-colored, semi-translucent yellow, or light brown solution

Often described in favorable terms

Noted for its strong rush in addition to its “long legs”

Perceived to be widely available

Unclear what other opioids or synthetics may be represented in these

products—not always stable day to day

Photos: E. Wheeler

Q: Let’s talk a little bit about it. So of these three types, what

we think might be traditional heroin, what we think might be a

mix and what we think might be more fentanyl, which one do

you prefer if you could find it on any given day?

A: I’d say the mix. The mix with the fentanyl and the dope.

Q: And how confident are you on any given day that you’ll be

able to find that?

A: Yeah, I can find it. Yeah, a hundred percent.

Liz, 25yo from Lawrence, MA

A: It’s weird because now with a lot of people the newest thing is the real heroin, the real dope, that is actually mixed also with fentanyl. So that way they get the intense feeling with the shelf life—trying to get the best of both worlds type thing so that you don’t get sick so often.

Q: So they’re mixing the fentanyl into the heroin to get a good fentanyl rush and the legs of the heroin? How long does it last then?

A: Well you’ll feel the fentanyl mixed with just the basic high anyway, so it’s intense at first. And then it’ll wear off but at least when it does completely wear off and you’re just functioning, you don’t have like a buzz or feel anything. You won’t be sick after. You know what I mean? Versus if it was straight fentanyl you would probably start to feel sick as close as 20 to 30 minutes; you’ll just feel sick right after.

Angela, 32yo from Lowell, MA

Photo: D. Ciccarone

*CHAT BOX*

Questions?Is fentanyl becoming the new

‘normal’ for your clients?

38

Harm Reduction Responses to Fentanyl

• Naloxone!

• Do a tester shot

• Slow shots

• Fentanyl test strips

• Take turns: stories of people going out at the same time

• Don't use alone

• Don’t delay calling 911 (Good Samaritan Laws)

• Syringe Exchange Programs

• Buprenorphine, “should be as accessible as fentanyl”

Naloxone

• Prescribed opioid antagonist which rapidly reverses opioid related sedation and respiratory depression and may cause withdrawal

• Overdose victims wake up minutes after administration

• Displaces opioids from the receptors for 30-90 minutes

• May be carried and administered by nonmedical people in NYS

OD Prevention Training – Essential Topics 1

• What does naloxone do?

• How to recognize an overdose?• Unconscious and you can’t wake them up

• Shallow or no breathing; breathing is often noisy: snoring, gurgling.

• Turning blue

• Actions:

• Shake and shout

• Use “sternal rub” a.k.a. “sternal grind”

OD Prevention Training – Essential Topics 2

• Call 911

• Administer naloxone• Nasal Spray: Person on back with head tilted back so that the

naloxone does not run down out of their nose• Spray: ½ up each nostril

OR• Intramuscular injection in the arm or thigh

• If no response, give the second dose in 2 minutes

• If breathing but very sick, Place person in “recovery position” so they will not choke if vomiting.

• Practice with device by trainee

OD Prevention Training – Essential Topics 3

• 911 not called?• If recovered OK, still stay for 3 hours

• If not OK, call 911 or take to ER

• Risk Factors• Mixing different drugs

• Reduced tolerance (incarceration, hospital, detox, rehab)

• Using alone

• Rescue Breathing

• Good Samaritan Law

Formulations

Are 2 doses enough?• Many governmental alerts for fentanyl and analogues

advise that extra doses of naloxone may be necessary.

• DOPE project did not find more than 2 doses necessary in 2015 • about ¼ of reversal took more than 5 minutes.

• Many anecdotal reports of extra doses turn out to have 3-6 doses administered in first few minutes

• Study of paramedics using Amphistar IN vs. Adapt IN• early trends show that same number of doses given despite

very different blood levels of each type. Adapt much higher.

• NYS Police use: only 7% given 3 doses

New York State naloxone initiative

• Community members: 400 programs - cohorts find high naloxone

use among people who use drugs

• Correctional facilities: Pilot in 10 State prison facilities being

expanded to others over 4000 kits distributed to inmates

• Law enforcement: Over 2800 administrations – mandated reporters

• Schools: Law allowing schools to stock and use naloxone

• Basic EMTs and firefighters: Added to scope of practice

• Pharmacy

Over 2000 pharmacies throughout NY State dispense naloxone under standing orders

• All chains with greater than 20 stores are required to dispense

• Type of device and copayment determined by individual’s insurance plan. Therefore: Ask your pharmacist

Naloxone in pharmacies

• DOPE Project distributes naloxone in San Francisco, directed by Eliza Wheeler from HRC

• 2015: fentanyl in both powder and pill form, pressed to mimic Xanax and sold as such

• Over 300 reported overdose reversals with naloxone in 3 months by trained participants

• 11 confirmed fentanyl-related deaths in 2015• More fatalities among opioid naive pill users (hard to contact)

• Fewer fatalities among heroin users who were injecting the powder fentanyl (reached through SEPs)

• Mostly used injectable naloxone (.4mg/1ml) for reversals

• This case is being prepared for publication by CDCEliza Wheeler, DOPE Project

Fentanyl and Naloxone Case Study

• Slow shot

• Tie off, place needle in vein, release tourniquet

• Very slowly inject

• Assess effects while needle still in vein

• Tester shot

• Small shot, to see if it produces the expected effect

• It is usually followed by a second, separate, shot

• Not a preferred option because of 2 separate tie-offs and punctures

Slow shots and tester shots

Urine test strips for fentanyl

• Can be used to test drugs for fentanyl

• Not FDA approved

• Manufactured in Canada by BTNX http://www.btnx.com/Product.aspx?id=16940

• Highly sensitive, very low false negative rate• does not cross-react with heroin• does cross-react with several analogues

• Used for testing drugs at Insite safe injecting facility (SIF) in Vancouver• Dealers bring drugs to test

• Being distributed for take-home testing through some SEPs in US, including NYC

• Do using test strips change behavior?• Reports from Insite suggest yes• Surveys distributed with strips in some locations; learn users reactions

Urine test strips for fentanyl

• Routine conversations with clients about fentanyl

• Advise clients to have a naloxone kit• Be trained on multiple types

• Advise clients to have someone who is aware of their substance use (family member, friend) to get trained in overdose prevention• Make sure they know where the overdose kit is

• Remind clients about Good Samaritan laws

• Remind clients to call 911

• Advise clients to not use alone and to use lessCollected from NYS SEPs by Allan Clear, NYS DOH

SEP Staff Strategies and Recommendations

52

Don’t delay calling 911

Good Samaritan Law: offers protection from charge and prosecution for possession of:

• Drugs up to an A2 felony offense (possession of up to 8oz of narcotics);

• Alcohol (for underage drinkers); • Marijuana (any amount); • Paraphernalia offenses; • Sharing of drugs (in NYS sharing constitutes

a “sales” offense).

53

Limitations of ‘Good Sam’

• Protects only overdoser and person calling 911

• Does not offer protection if:• Previous conviction for class A-1, A-2, B

felony possession (B = over ½ lb. of marijuana)

• open warrant for arrest or currently on probation/parole.

• Other crimes on scene

Opioid Treatment Overview

• Opioid maintenance is the most effective treatment for heroin addiction

• Often combined with psychosocial treatment

• Opioid maintenance may be compared to the treatment of diabetes with insulin

NIH Consensus Statement on Heroin Addiction 1997

Methadone

• Implemented as treatment of opioid use disorder established in 1966 FDA approved in 1972

• Oral opioid agonist given daily

• Highly effective in reducing heroin use with associated decreases in risk behaviors

• Gold standard in treatment of opioid use disorders

Methadone: restricted accessAvailable only in methadone clinics

• Many areas lack sufficient methadone treatment slots

• Requires 6 day a week visits with possible progression to a less burdensome schedule

• Many users do not enter methadone programs, probably because of the restrictions and stigma

NIH Consensus Statement 1998, Rettig IOM 1995

Buprenorphine

• FDA approved in 2002

• Prescribers may take an 8 hour course, apply for a waiver from the DEA to prescribe in their own office with visits as agreed upon

• Sublingual medication may be taken daily or sometimes every other day

• Probably an equal in results to methadone

Higher safety profile

Difficult to overdose on buprenorphine alone

▪ “Partial agonist”- a ceiling effect above which higher doses do not increase activity - respiratory depression leading to fatal overdose unlikely

▪ Overdoses are rare and usually related to mixing with benzodiazepines AND injecting

▪ Young children can overdose; keep out of reach!

Ling JSAT 2002

*CHAT BOX* What strategies can you suggest?Comments on those discussed?

Questions?

Acknowledgements

• New York State Department of Health

• New York City Department of Health

• Overdose Safety with Naloxone Network (aka Naloxone Overdose Prevention Education group (NOPE))

• Daniel Ciccarone, MD, MPH, at USF

• Jon Zibbell, PhD

• Mary Wheeler, Northeast Behavioral Health: Healthy Streets Outreach Program, Lynn, MA