Naloxone for Opioid Safety Phillip O. Coffin, MD MIA San Francisco Department of Public Health University of California San Francisco
Disclosure Information Gilead, Donated ledipasvir-sofosbuvir, Study, 2016-present Alkermes, Donated ER-naltrexone, Study, 2014-2015
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.
Lay Naloxone Reversals Fentanyl-Related Deaths 140 120 100 80 60 40 20 0 Jan Feb Mar Apr May Jun Fentanyl powder Counterfeit Xanax Jul Aug Sep Oct Nov Dec 7 6 5 4 3 2 1 0 Source: Drug Overdose Prevention/Education Project, San Francisco
Scottish Naloxone Program, Pre-Release - 36% reduction in opioid-related deaths in the 4 weeks postrelease - At least 1 death averted per 285 kits distributed Deaths / 1000py Out of Treatment ~4.3 Residential Treatment In 3.9 1-28 days out 18.8 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. 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. 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.
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.
Positive - More cautious about dosing or timing - Improved knowledge about opioids and overdose - Reduced polysubstance use - Not using opioids alone 37% 0% 63% Neutral 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 No need for clinicians Standing orders Some products OTC? Insurance coverage
New terminology for overdose Indications for co-prescribing Naloxone in treatment programs / relapse risk Implementation strategies Optimal dosing regimen
Percent of All Naloxone Reversals 100% 80% 0.37 0.32 0.37 0.38 60% % reversed with 1.5-2 doses 40% % reversed with 1 dose % OD deaths involving fentanyl 20% 0.53 0.61 0.58 0.55 0% 2013 2014 2015 2016 Source: Prevention Point Pittsburgh
20% 10% 0% Santa Fe (N=95) North Carolina (N=6) San Francisco (N=702) Source: Santa Fe Mountain Center; North Carolina Harm Reduction Coalition, DOPE Project
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.