Background: In the US, approximately 28,000 opioid overdose deaths occur annually, with at least half of these deaths involving prescription opioids (1). This Fast Fact discusses the use of naloxone in the outpatient setting for patients with an advanced illness on opioid therapy who may be at risk for opioid overdose.  See Fast Fact #39 for further information on naloxone use for inpatient care settings. 

Opioid overdose in palliative care patients:  Previous studies have suggested that opioid overdoses are infrequent for patients receiving palliative care (2). In recent years, however, palliative care clinicians have been more routinely involved in the outpatient treatment of cancer pain and, in some instances, may also manage pain in long-term cancer survivors and/or non-cancer pain (2-4). Therefore, there is concern that many palliative care patients at home and bystanders may be at risk for opioid overdose given their co-morbidities, relatively high doses of opioids needed to control symptoms, and, in some instances, a history of substance use disorders (see Fast Fact #127, Fast Fact #310, and Fast Fact #311) (5). There is also an emerging awareness of inappropriate or excessive use of opioids among patients with cancer-related pain (2).   

Naloxone co-prescribing:  In the 1990s, public health and community organizations initiated naloxone distribution programs such as the Overdose Education and Naloxone Distribution (OEND) to prevent opioid overdose fatalities among heroin users (6). Between 1996 and 2010, naloxone was distributed to 50,000 persons, and more than 10,000 overdose reversals were documented (7). In many scenarios, bystanders were able to recognize an overdose from a prescribed opioid and administer intranasal (IN) naloxone effectively. Federal agencies from the US, Canada, Australia, and many European countries have endorsed the provision of IN naloxone as part of a larger strategy to reduce overdose fatalities from prescribed opioids (6,8).  

Pharmacology:  Naloxone is an opioid antagonist indicated for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression. A needle-free formulation which is FDA approved for the emergency treatment of an opioid overdose is available via a pre-filled, single dose IN spray.  IN naloxone begins to reverse opioid-induced respiratory depression and sedation in 8-13 minutes; peak effect is 20-30 min; and the half-life is about 2 hours (9). The nasal spray is supplied in a box containing two, 4 mg single-use nasal spray devices. An IN dose can be repeated every 2-3 minutes in alternating nostrils, if necessary and is non-inferior to intravenous naloxone (8,10). In many states, it is available without a prescription in pharmacies and public health vending machines (11,12).  

Indications for outpatient IN naloxone prescribing:  Major guidelines from the Centers of Disease Control and Veterans Affairs exclude palliative care patients from their recommendations to offer IN naloxone to all patients prescribed scheduled opioids. There is a concern that bystanders may administer naloxone inappropriately in seriously ill patients when physiological changes related to disease progression are mistakenly thought to be related to an overdose. This may not be as large of a concern as originally thought and furthermore, the concern from a potential opioid overdose of a bystander now seems to compel many palliative care clinicians to routinely prescribe IN naloxone for patients on long-term opioid therapy (13). The final decision about co-prescribing naloxone should be individualized based on a patient’s risk profile, prognosis, care preferences, and the availability of an informed caregiver. Establishing more rigorous evidence-based criteria for co-prescribing is needed, but the following patients may be at risk of an opioid-related fatality when death is not imminently anticipated (14): 

• Daily morphine equivalent doses of > 60 mg/day (15,16)
• Methadone as a prescribed analgesic (17)
• Benzodiazepines and/or antidepressants in combination with opioids (18)
• History of unintentional or intentional overdose (19)
• History of a substance use disorder including alcohol or tobacco (20)
• History of chronic pulmonary, renal, or hepatic disease (15)
• A recent history of incarceration (21)

Patient information:  Patients and their caregivers should be educated on how to properly identify an opioid overdose and how to administer IN naloxone. Informational handouts are available for patients and their family members (see reference #22). Interpretative guidance from the US Department of Health and Human Services Office of Civil Rights indicates that HIPPA regulations allow clinicians to share information to loved ones in the event of a health emergency such as an opioid overdose when the patient is made incapacitated by opioids and/or there is a serious threat to his or her health or safety (23).  Patients and caregivers should be advised to call 911 with any administration of naloxone (22). Naloxone should NOT be administered to patients with comfort goals of care who are imminently dying.  This recommendation needs to be clearly communicated to caregivers of patients to avoid inappropriate use. The adverse effects of naloxone administration are primarily opioid-withdrawal related however precipitation of a pain crisis is of serious concern (24).

References:  

1. “Injury Prevention & Control: Opioid Overdose,” Centers for Disease Control and Prevention, last updated March 16, 2016, http://www.cdc.gov/drugoverdose/index.html.
2. Bruera E, Paice JA. Cancer pain management: safe and effective use of opioids. Am Soc Clin Oncol Educ Book. 2015;35:e593-9. doi:10.14694/EdBook_AM.2015.35.e593.
3. 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.
4. Chwistek M, Ewerth N. Opioids and Chronic Pain in Cancer Survivors : Evolving Practice for Palliative Care Clinics. J Palliat Med.  2016;19(3):19111. doi:10.1089/jpm.2015.0471.
5. Tan PD, Barclay JS, Blackhall LJ. Do Palliative Care Clinics Screen for Substance Abuse and Diversion? Results of a National Survey. J Palliat Med. 2015;18(9):752-757. doi:10.1089/jpm.2015.0098.
6. Mueller SR, et al. A Review of Opioid Overdose Prevention and Naloxone Prescribing: Implications for Translating Community Programming Into Clinical Practice. Substance Abuse 2016; 36(2):240-253.
7. Community-based opioid overdose prevention programs providing naloxone—United States, 2010. MMWR Morb Mortal Wkly Rep. 2012;61:101–105.
8. Oliva EM, Nevedal A, Lewis ET, et al. Patient perspectives on an opioid overdose education and naloxone distribution program in the U.S. Department of Veterans Affairs. Subst Abus. 2016;37(1):118-126.
9. Naloxone (Narcan) nasal spray for opioid overdose. Medical Letter on Drugs and Therapeutics 2016; 58(1485):1-2.
10. Merlin MA, Saybolt M, Kapitanyan R, et al. Intranasal naloxone delivery is an alternative to intravenous naloxone for opioid overdoses. Am J Emerg Med. Mar 2010;28:296–303.
11. Allen ST, O’Rourke A, Johnson JA, et al.  Evaluating the impact of naloxone dispensation at public health vending machines in Clark County, Nevada. Addiction 2022; 54(1):2680-2688.
12. National Harm Reduction Coalition. Find harm reduction resources near you. 2024.  Available at: Harm Reduction Resources Near You | National Harm Reduction Coalition. Last accessed February 9, 2024.
13. Marks S, Patel D, Amjad R, et al.  A regional survey of attitudes and experiences in determining when to prescribe intranasal naloxone for patients seen in palliative care clinics in the Unites States of America.  Palliative Medicine Reports 2024; 5(1):286-292.
14. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016. Jama. 2016;315(15):1624-1645. doi:10.1001/jama.2016.1464.
15. Bohnert AS, Valenstein M, Bair MJ, et al. Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA. 2011;305:1315–1321.
16. Dunn KM, Saunders KW, Rutter CM, et al. Opioid prescriptions for chronic pain and overdose: a cohort study. Ann Intern Med. 2010;152:85–92.
17. Walley AY, Doe-Simkins M, Quinn E, Pierce C, Xuan Z, Ozonoff A. Opioid overdose prevention with intranasal naloxone among people who take methadone. J Subst Abuse Treat. 2013;44:241–247.
18. Hall AJ, Logan JE, Toblin RL, et al. Patterns of abuse among unintentional pharmaceutical overdose fatalities. JAMA. 2008;300:2613–2620.
19. Coffin PO, Tracy M, Bucciarelli A, Ompad D, Vlahov D, Galea S. Identifying injection drug users at risk of nonfatal overdose. Acad Emerg Med. 2007;14:616–623.
20. Evans JL, Tsui JI, Hahn JA, Davidson PJ, Lum PJ, Page K. Mortality among young injection drug users in San Francisco: a 10-year follow-up of the UFO study. Am J Epidemiol. 2012;175:302–308.
21. Binswanger IA, Stern MF, Deyo RA, et al. Release from prison—a high risk of death for former inmates. N Engl J Med. 2007;356:157–165.
22. Substance Abuse and Mental Health Services Administration – Opioid Overdose Toolkit. Overdose Prevention and Response Toolkit | SAMHSA Publications and Digital Products Accessed September 23, 2024.
23. US Department of Health and Human Services Office for Civil Rights.  How HIPPA allows doctors to respond to the opioid crisis.  https://www.hhs.gov/civil-rights/for-individuals/special-topics/opioids/index.html.  Accessed December 19, 2024.
24. Buajordet I, Naess AC, Jacobsen D, Brors O. Adverse events after naloxone treatment of episodes of suspected acute opioid overdose. Eur J Emerg Med. 2004;11:19–23.

Authors’ Affiliation: Fox Chase Cancer Center; Temple University Health System; Philadelphia PA
Conflicts of Interest: None 
Version History:  Edited by Sean Marks MD, first electronically published January 2017; updated in April 2019; updated again in September 2024.