Transcript WHO says Narcan?Intranasal that is!

Deb Wagner, PharmD,
FASHP
Associate Professor
Pharmacy/Anesthesiology
October 2015
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Review the background
on the current opioid
crisis
Describe the recent
interest in the use of
prehospital naloxone for
suspected opioid
overdoses
Identify risks and
benefits associated with
it’s use
Identify it’s current role
in practice
WHO Library Cataloguing-in-Publication Data
Community management of opioid overdose.
010
Deaths per 100,000 population
18
Motor vehicle
traffic
Poisoning
16
14
12
Drug
poisoning
Unintentional
drug poisoning
10
8
6
4
2
0
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010
NOTES: Drug poisoning deaths are a subset of poisoning deaths. Unintentional drug poisoning deaths are a subset of drug poisoning deaths.
SOURCE: CDC/NCHS, National Vital Statistics System; and Warner M, Chen LH, Makuc DM, Anderson RN, Miniño AM. Drug poisoning deaths in the United
States, 1980–2008. NCHS data brief, no 81. Hyattsville, MD: National Center for Health Statistics. 2011.
http://www.cdc.gov/nchs/data/databriefs/db81.htm. Intercensal populations http://www.cdc.gov/nchs/nvss/bridged_race/data_documentation.htm
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Steady rise in drug overdose deaths since
1992
117% increase from 1999 to 2012
In the United States (US), 100 people die
every day from opioid overdose
>16,000 people died from an overdose of
prescription opioids in US in 2013
NOTE: Access data table for Figure 3 at:
http://www.cdc.gov/nchs/data/databriefs/db166_table.pdf#3.SOURCE:
CDC/NCHS, National Vital Statistics System, Mortality File.
NOTE: Access data table for Figure 3 at:
http://www.cdc.gov/nchs/data/databriefs/db166_table.pdf#3.SOURCE: CDC/NCHS,
National Vital Statistics System, Mortality File.
JAMA. 2008;300(22):2613-2620. doi:10.1001/jama.2008.802
Data from Michigan Department of
Community Health
Approximately 2% of
heroin users die each
year
 ½-2/3 of heroin users
experience at least one
nonfatal overdose
 80% have observed an
overdose
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Sporer BMJ 2003, Coffin Acad Emerg Med 2007
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People coming out of jail or treatment have
highest risk of overdose
Most deaths are among opiate users who are
in their late twenties to early thirties and have
been actively using for the past five to ten years
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Only 17 % of opiate related deaths are among
new users.
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New Drug Use Patterns
 New Initiates to prescription drugs
 Vicodin/Percocet/oxycodone >>> heroin
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Heroin Availability/Purity/Lethal Mixture
 Heroin is the leading drug threat in New England
 From ‘93-’10 Heroin reported as primary drug increased from 20% - 40%
of treatment admissions in MA
 Combination with Fentanyl
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Prescribing Patterns
 Schedule II Opioid prescriptions increased more than 4 fold from 1999-
2010
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Male gender
Older age
Lower socioeconomic status
Mental health disorders
Higher doses ≥ 100mg morphine equivalents
daily
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Polypharmacy
JAMA. 2008;300(22):2613-2620. doi:10.1001/jama.2008.802
Knowlton A. Prehospital Emergency Care. 17; 2013
Knowlton A. Prehospital Emergency Care. 17; 2013
Knowlton A. Prehospital Emergency Care. 17; 2013
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$20.4 billion per year in 2009
 $2.2 billion direct costs
▪ inpatient, ED, MDs, ambulance
 $18.2 billion indirect costs
▪ lost productivity from absenteeism and mortality
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$37,274 cost per opioid overdose event
Inocencio TJ et al. Pain Medicine 2013
Inocencio. Pain Med. 14; 2013
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One heroin overdose death prevented for every 164 kits
distributed
Cost for naloxone distribution would range between:
 $438-$14,000 (best-worst case scenario) for every qualityadjusted life year gained
Generally accepted threshold is $50,000/year
 For dialysis: recently calculated as $129,000
▪ Lee et al. Value Health 2009;12(1): 80-7.
 For primary care-based SBIRT: recently calculated as
$6960
▪ Tariq et al. PLoS One 2009;4(5)
Coffin and Sullivan. Ann Intern Med. 2013; 158: 1-9.
Inocencio TJ. Pain Med. 14; 2013
WHO PAYS?
All 53 jurisdictions permit
Paramedics to administer naloxone
 Of the 48 jurisdictions with
mid-level EMS personnel, all but
one authorize those personnel to
administer naloxone
 Only twelve jurisdictions explicitly permit EMTs
to administer naloxone
 Five additional states permit some or all EMTs to
administer the drug through pilot programs or
agency medical director authority
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Davis, Walley, Dailey, Southwell, Neihaus, “EMS Naloxone Access:
A National Systematic Legal Review”, Academic EM, August 2014
Opioids are used primarily in medicine for pain relief,
treatment of opioid use disorders, and cough relief.
Opiates
Opioids
Natural
Semi-synthetic
Fully synthetic
opium
morphine
codeine
heroin
hydrocodone
oxycodone
fentanyl
methadone
meperidine
All categories have overdose risk
 Weak/Thready
pulse
 Slow or Absent
Respirations
 Constricted Pupils
 Weakness
 Unresponsiveness
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MOA: Competitively displaces opioids from
receptors
Half-life: ~ 30 min-1 hour
Complete, temporary reversal of opioid
overdose effects
May cause acute and severe opioid
withdrawal
Inactivated by first pass metabolism
Grassin-Delyle S. Pharmacol Therap. 134; 2012
NASAL PHYSIOLOGY
Chhajed S. Int J Pharm Sci Res. 6; 2012
ABSORPTION PATHWAYS
NOSE TO BRAIN TRANSPORT
PLASMA VS CSF
CONCENTRATIONS
NI
IV
Illum L. Eur J Pharm Sci. 11; 2000
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The more lipophilic the better
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Smaller is better
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Volume is important
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Increase nasal residual time
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Enhance nasal absorption
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Modify drug to change the physiochemical
properties
Product
Route of
Administration
Available
Strengths
Dosing
Advantage
Price per
Dose*
(7/2015)
FDA
Status
Autoinjector
IM
0.4mg/ml
0.4mg
No training
required
Easy to use
No
assembly
Decreased
risk of
needle stick
$345
Yes
Multi-use
Vial
IM, IV, SC
0.4mg/ml
0.4mg
Multiple
doses
$11.84
Yes
Single
Dose Vial
IM, IV, SC
0.4mg/ml
0.4mg
Individual
dose
$18.99
Yes
Prefilled
Syringe
Intranasal
1mg/ml
1mg
Easy to use
Decreased
risk of
needle stick
$19.80
Yes
Robertson TM. Prehospital Emergency Care 13; 2009
LEVEL OF CONSCIOUSNESS
RESPONSE COMPARISON
NS
Sabzghabaee AM. Arch Med Sci 10; 2014
Kelly A. MJA. 182; 2005
0.15mg/kg
Morphine
0.4mg
Naloxone
Dahan A Anesthesiology. 2010;112
Dahan A. Anesthesiology. 2010; 112
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First case in 1977
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Occurs with doses as low as 80mcg IV
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Onset within 1-60 minutes
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Majority in healthy men < 50 yo
Congeni A. Em-News.com. July 2015
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Increases catecholamine release
 especially in the presence of hypercapnoea
 The correction of of hypercapnoea reduces
haemodynamic effects.
▪ Mills CA (1988)
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There is no clinical evidence to support
hypercapnoea correction prior to
administration of naloxone.
Mills CA. Anesth Anal. 1988
Mills CA. Anesth Anal. 1988
The Solution
• A multi-faceted
approach to
overdose
prevention is
required.
PREVENTION &
E D U C AT I O N
MONITORING & DIVERSION
CONTROL
INTERVENTION &
T R E AT M E N T
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Prescription monitoring programs
▪ Paulozzi et al. Pain Medicine 2011
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Prescription drug take back events
 Safe disposal
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Safe opioid prescribing education
▪ Albert et al. Pain Medicine 2011; 12: S77-S85
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Expansion of opioid agonist treatment
▪ Clausen et al. Addiction 2009:104;1356-62
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Safe injection facilities
▪ Marshall et al. Lancet 2011:377;1429-37
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Feasibility
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Piper et al. Subst Use Misuse 2008: 43; 858-70
Doe-Simkins et al. Am J Public Health 2009: 99: 788-791
Enteen et al. J Urban Health 2010:87: 931-41
Bennett et al. J Urban Health. 2011: 88; 1020-30
Walley et al. JSAT 2013; 44:241-7 (Methadone and detox programs)
Increased knowledge and skills
▪ Green et al. Addiction 2008: 103;979-89
▪ Tobin et al. Int J Drug Policy 2009: 20; 131-6
▪ Wagner et al. Int J Drug Policy 2010: 21: 186-93
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No increase in use, increase in drug treatment
▪ Seal et al. J Urban Health 2005:82:303-11
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Reduction in overdose in communities
▪ Maxwell et al. J Addict Dis 2006:25; 89-96
▪ Evans et al. Am J Epidemiol 2012; 174: 302-8
▪ Walley et al. BMJ 2013; 346: f174
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1999-2004 Largest increase in drug overdose
mortality rates
295 unintentional deaths from
pharmaceutical overdose
93% from opioids
90% were men age 18-70 yo
63% were associated with drug diversion
21% due to doctor shopping
Substance abuse indicators present in 95%
Cobaugh DJ. AJHP. 71; 2014
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Enrollments
 16,379 individuals
 >10 per day
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AIDS Action Committee
AIDS Project Worcester
AIDS Support Group of Cape Cod
Brockton Area Multi-Services Inc. (BAMSI)
Bay State Community Services
Boston Public Health Commission
Greater Lawrence Family Health Center
Holyoke Health Center
Learn to Cope
Lowell House/ Lowell Community Health Center
Manet Community Health Center
Northeast Behavioral Health
Seven Hills Behavioral Health
Tapestry Health
SPHERE
• Rescues
– 1,741 reported
– >1 per day
Witnessed overdose ever
Lifetime history of overdose
Received naloxone ever
Inpatient detox, past year
Incarcerated, past year
Reported at least one overdose
rescue
User
n=11,002
75%
49%
41%
64%
28%
Non-User
n=5,377
42%
7.5%
2.0%
Program data
N=1,741
Deaths
7 / 1729
0.4%
OD requiring 3 or more doses
72 / 1604
4%
Recurrent overdose
3/1741
0.2%
Withdrawal symptoms after naloxone
107/219
49%
Difficulty with device
11/1741
0.6%
Negative interactions with public safety
114/ 466
24%
205 / 5271
4%
Confiscations
Program data
NALOXONE COVERAGE PER
100K
250
OPIOID OVERDOSE DEATH
RATE
100%
90%
200
80%
70%
150
60%
50%
100
50
40%
No
coverage
30%
1-100 ppl
20%
10%
0
27%
reduction
46%
reduction
100+ ppl
0%
Walley et al. BMJ 2013; 346: f174.
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Prescription and prescriber
typically required
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Naloxone cost is increasing,
funding is minimal
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Missing people who don’t
identify as drug users, but
have high risk
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CBOs target IDU, people w/
substance use disorders,
HIV prevention
• Co-prescribe naloxone with
opioids for pain
• Co-prescribe with
methadone/ buprenorphine
for addiction
• Insurance should fund this
• Increase patient, provider &
pharmacist awareness
• Universalize overdose risk
Opioid overdose is a
public health crisis
 Naloxone is a safe and
effective opioid
reversal agent
 Multiple routes of
administration are
available
 Diversion and
prescribing of opioids
must be addressed
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