Phillip O. Coffin, MD MIA

San Francisco Department of Public Health University of California San Francisco

Naloxone for Opioid Safety

Gilead, Donated ledipasvir-sofosbuvir, Study, 2016-present Alkermes, Donated ER-naltrexone, Study, 2014-2015

Disclosure Information

1. Role / Effectiveness of Lay Naloxone

2. Potential impact of OTC status

3. Research gaps

Source: Darke S, Mattick RP, Degenhardt L. The ratio of non-fatal to fatal heroin overdose. Addiction. 2003 Aug;98(8):1169-71.

Source: Wheeler E, Jones TS, Gilbert MK, Davidson PJ. Opioid Overdose Prevention Programs Providing Naloxone to Laypersons - United States, 2014. MMWR. 2015;64(23):631-635.

Naloxone is not a controlled substance

States on this map have added legal protections, such as authorizing:

Prescribing/dispensing to potential bystanders Third-party administration by lay bystanders Prescribing/dispensing by standing order or directly from pharmacies

States in green also have laws protecting from prosecution when help is sought

Source: www.lawatlas.org

Predictors of Using Naloxone to Reverse an Overdose

Adjusted Odds Ratio

Use heroin 1.85

Use methamphetamine 1.71

Previously witnessed OD 2.02

Source: Rowe C, Santos GM, Vittinghoff E, Wheeler E, Davidson P, Coffin PO. Predictors of participant engagement and naloxone utilization in a community-based naloxone distribution program. Addiction. 2015;110(8):1301-1310.

Sources: Walley et al., Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: interrupted time series analysis. BMJ. 2013;346:f174; Davidson et al., Naloxone distribution to drug users in California and opioid-overdose death rates. Drug & Alc Dep. 2015; 156: e54.

Source: Coffin PO, Sullivan SD. Cost-effectiveness of distributing naloxone to heroin users for lay overdose reversal. Ann Intern Med. 2013;158:1-9.

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Fentanyl powder

Counterfeit “Xanax”

Source: Drug Overdose Prevention/Education Project, San Francisco

Source: Binswanger IA, Blatchford PJ, Mueller SR, Stern MF. Mortality after prison release: opioid overdose and other causes of death, risk factors, and time trends from 1999 to 2009. Ann Intern Med. 2013;159(9):592-600.

Deaths / 1000py

Out of Treatment ~4.3

Residential Treatment

In 3.9

1-28 days out 18.8

Source: Pierce M, Bird SM, Hickman M, et al. Impact of treatment for opioid dependence on fatal drug-related poisoning: a national cohort study in England. Addiction. 2016;111(2):298-308.

Scottish Naloxone Program, Pre-Release - 36% reduction in opioid-related deaths in the 4 weeks post-

release - At least 1 death averted per 285 kits distributed

Source: Bird SM, McAuley A, Perry S, Hunter C. Effectiveness of Scotland’s National Naloxone Programme for reducing opioid-related deaths: a before (20076-10) versus after (2011-13) comparison. Addiction. 111:883-891.

“Overdose prevention, including prescribing or dispensing naloxone, is an essential complement to both detoxification services as well as medically supervised withdrawal”

Source: Coffin PO, Behar E, Rowe C, et al. Nonrandomized intervention study of naloxone coprescription for primary care patients receiving long-term opioid therapy for pain. Ann Intern Med. 2016.

63% 0%

37%

Neutral Positive - More cautious about dosing

or timing - Improved knowledge about

opioids and overdose - Reduced polysubstance use - Not using opioids alone

Source: Behar E, Rowe C, Santos G-M, Murphy S, Coffin PO. Primary Care Patient Experience with Naloxone Prescription. Annals of Family Medicine. 2016;14:431-6.

Patient Characteristics (N=60) Percent

History of overdose 37%

Overdose 20%

“Bad reaction” consistent with overdose 17%

Perceived risk of personal overdose Low (2 / 10)

Source: Behar E, Rowe C, Santos G-M, Murphy S, Coffin PO. Primary Care Patient Experience with Naloxone Prescription. Annals of Family Medicine. 2016;14:431-6.

Interviewer: How many times would you say you’ve had these bouts of

delirium, or you’ve stopped breathing because of

opioids?

Patient: Ever? 8-10 times.

Interviewer: And how many times has [naloxone] been used on you?

Patient: Oh boy. That would be really hard to answer. I’d say

somewhere in the neighborhood of 12-15 times.

Interviewer: So, around 12-15 times someone has given you [naloxone]

because you’ve stopped breathing because of opioids?

Patient: Yes. Medical staff each time. Because of the opioids, I’ve

stopped breathing.

Interviewer: Over what period of time?

Patient: Over 1 year.

Source: Behar E, Rowe C, Santos G-M, Murphy S, Coffin PO. Primary Care Patient Experience with Naloxone Prescription. Annals of Family Medicine. 2016;14:431-6.

“Clinicians should incorporate into the management plan strategies to mitigate risk, including considering offering naloxone when factors that increase risk for opioid overdose, such as history of overdose, history of substance use disorder, higher opioid dosages (>50 MME/day), or concurrent benzodiazepine use, are present.”

OTC Access Prescription Only

Insurance coverage

Standing orders

Some products OTC?

No need for clinicians

New terminology for overdose

Indications for co-prescribing

Naloxone in treatment programs / relapse risk

Implementation strategies

Optimal dosing regimen

0.53 0.61 0.58 0.55

0.37 0.32 0.37 0.38

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2013 2014 2015 2016

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% reversed with 1.5-2 doses

% reversed with 1 dose

% OD deaths involving fentanyl

Source: Prevention Point Pittsburgh

Source: Santa Fe Mountain Center; North Carolina Harm Reduction Coalition, DOPE Project

0%

10%

20%

Santa Fe (N=95) North Carolina (N=6) San Francisco (N=702)

People who use drugs are in best positioned to utilize lay naloxone

While OTC access would partly alleviate logistic barriers, the major barrier is cost

Co-prescribing naloxone with opioids is feasible and may have ancillary benefits

More research is needed regarding overdose terminology, naloxone in SUD treatment settings, dosing strategies, and implementation.