How to save a life with naloxone

Case Scenario 

Adnan, 35, has been using heroin on and off since becoming homeless at the age of 15. He comes into the pharmacy to ask about naloxone. Adnan explains that many years ago he found a woman on the floor of a bathroom, unresponsive, with blue lips and barely breathing. He panicked and tried to shake her awake, but she died in front of him. Adnan has always tried to be cautious with his own opioid use but has had to call the ambulance several times for others. 

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Introduction

Collectively, opioids are the group of drugs most often implicated in unintentional drug-related deaths.¹ In this article, ‘opioids’ is used as the umbrella term to cover pharmaceutical opioids and illicit substances such as heroin. Naloxone is an opioid receptor antagonist which can reverse the effects of opioid toxicity (or ‘overdose’), including life-threatening respiratory depression.^2,9 It can be safely administered by any trained layperson, such as a peer or family member, in the form of a nasal spray or intramuscular (IM) injection. By providing non-judgemental and appropriate counselling on the use of naloxone, pharmacists can empower those who carry it to confidently intervene in the case of opioid toxicity. 

Epidemiology 

In 2020, 856 Australians were reported to have died following an unintentional opioid overdose. This is a growing problem, with numbers nearly tripling since 2006. During this time, deaths attributed to heroin increased by 500%, and those involving fentanyl, pethidine or tramadol increased by almost 1,300%.¹ It has been found that those who survive an overdose are at greater risk of mortality from subsequent overdoses. In particular, being male, over 35, with a history of being attended to by an ambulance recently or on multiple occasions, is associated with an increased risk of death.^3,4

Pathophysiology 

The physiological effects of opioids can be explained primarily by their activation of mu opioid receptors.^5,9 This is responsible for the opioid effects of analgesia, respiratory depression (decrease in respiratory rate and depth) and the feelings of euphoria experienced by many people who use opioids.^5,6 Other effects of mu receptor activation include sedation, miosis and constipation.5 Fatalities occur secondary to end-organ damage resulting from hypoxia.^5,7

Clinical features of toxicity 

Opioid toxicity is frequently characterised by a trio of clinical features: CNS depression, respiratory depression and miosis. However, the absence of miosis does not exclude opioid toxicity, particularly in the context of a mixed overdose with more than one substance.^8,9 Other potential signs include cyanosis, cold and clammy skin, slow breathing, difficulty rousing, or gurgling and snoring noises.¹⁰

Naloxone 

Naloxone is a semisynthetic morphine derivative that acts as a competitive antagonist at opioid receptors. When administered to someone with opioid toxicity, it effectively and rapidly reverses the effects of the opioid, including respiratory and CNS depression^9,11 and will reverse the effects of all commonly used opioids, including fentanyl.¹²

The primary aim of treatment with naloxone in the community is to maintain the person’s breathing, and secondarily to increase their conscious level to allow them to support their own airway, while waiting for emergency services.⁸

Naloxone is short-acting, wearing off in 30–90 minutes. All patients administered naloxone should be monitored for recurrence of symptoms (e.g. sedation, respiratory effects) as a result of this.¹¹

This is particularly likely to occur with longer-acting opioids such as buprenorphine or methadone, or with extended-release products, and the patient may require ongoing management in hospital.^11,14

Naloxone is considered safe to use during breastfeeding, and there is no evidence of teratogenicity associated with use while pregnant.^13,15 The lowest effective dose should ideally be used to minimise the risk of acute withdrawal in pregnant patients.¹⁵

Take Home Naloxone (THN) program 

In 2019, the Australian Government initiated the THN pilot program in New South Wales, South Australia and Western Australia. This program allowed those at risk of experiencing or witnessing an opioid overdose or adverse reaction to access naloxone without cost and without a prescription. During the trial, naloxone was administered 1,649 times and was estimated to have saved at least three lives per day.¹⁶

As a result of the trial’s success, from July 2022 naloxone was made available for free and without a prescription from approved providers with Commonwealth funding. This includes all participating pharmacies across each state and territory of Australia. 

Key points pharmacists need to know about the program 

• Naloxone is a Pharmacist Only medicine (Schedule 3) when used for the treatment of opioid overdose. 
• Pharmacists should identify individuals who may benefit from having an emergency supply of naloxone on hand (i.e. any person who is likely to experience or witness an opioid overdose or adverse reaction involving either prescribed or illicit opioids), and supply naloxone with appropriate counselling.¹³ It is important to note that naloxone is very rarely self-administered, hence the importance of identifying individuals – such as the friends and peers of people who use opioids – who may witness an overdose and ensuring they know how to use naloxone.^2,29
• If possible, as part of your responsibilities in supplying scheduled medicines, gather sufficient information to assess the safety and appropriateness of naloxone for the individual. However, supply should not be denied on the basis of insufficient information, due to the life-saving nature of this treatment.¹³
• Risk factors that may increase the risk of opioid-related harms include^13,17:
  • daily dosages of opioids exceeding 50 mg oral morphine equivalents
  • the use of long acting or extended-release opioid preparations
  • concurrent use of sedatives or alcohol or comorbidities including lung disease or impaired hepatic or renal function
  • use of illicit drugs, particularly where the drug content is unknown.
• Naloxone is available in ampoules, as a pre-filled syringe or as a nasal spray.² Consumer preferences should assist in choosing the appropriate formulation to supply. Intranasal administration may be preferred by some (due to ease of use and avoidance of the risk of accidental needlestick injury); however, an injectable formulation may be preferable for those who use injectable substances. Despite minor pharmacokinetic differences, the nasal spray has been found to be comparable to injectable forms in terms of clinical benefit.¹⁸
• The individual can be supplied a maximum of two times the PBS maximum quantity (or unit) per visit; for example: two boxes of Nyxoid nasal spray (i.e. total of four nasal sprays), or two boxes of ampoules (Juno or DBL – e.g. 10 ampoules in total), or two boxes of Prenoxad pre-filled syringe.² The individual can be supplied two units of the same product or one unit each of two different products.¹⁹
• There is no limit to the number of times an individual can visit and be supplied naloxone at no charge under the program.¹⁹
• Appropriate counselling and education are required for each supply. 
• The participant does not need to provide any identification or Medicare details to access naloxone under the program. Verbal consent is required to collect de-identified data relating to the supply; however, naloxone can still be supplied if the individual does not consent to this process. 
• Participating pharmacies are reimbursed for supplying naloxone, including a dispensing fee.²⁰ Reimbursement is claimed through the PPA after submission of supply details (i.e. date of supply, who supplied and the form/quantity given) and any de-identified patient data (if available).^19,20
• Pharmacists can refer to the program information available from the PPA for more information, including how pharmacies Australia-wide can register to participate (www.ppaonline.com.au/ take-home-naloxone).

Counselling for take-home naloxone 

Given that naloxone is not intended to be self-administered (the person may be unconscious, or awake but unable to talk), friends, family and peers should be familiar with how to recognise and manage opioid overdose including how to administer naloxone.^2,13

People who use drugs often face stigma within the community, which in turn creates a barrier to seeking help.21 When counselling on the use of naloxone, or providing support post-overdose, care should be taken to avoid the use of discriminatory or reductive language such as ‘junkie’, ‘druggie’ or ‘drug abuser’.²² Using person-centred language such as ‘person who uses drugs’ or ‘person with a dependence on heroin’ is more likely to be associated with a positive experience for the consumer and better long-term health outcomes.²³

Key points to include when counselling on naloxone 

• Naloxone is used for the emergency treatment of known or suspected opioid overdose or toxicity.^13,20 Naloxone has minimal adverse effects/essentially no pharmacological activity when used in the absence of opioids.^11,13
• Provide an opioid overdose plan and ensure the person using opioids and/or the third party understands it. This plan details the signs of an opioid overdose and what steps should be followed in an emergency. Opioid overdose response plans are available to download (www. penington.org.au/workforcedevelopment/naloxone-training).¹³
• Explain correct dosing and administration of naloxone. 
• Explain that naloxone is short-acting, with effects expected to last 30–90 minutes. It is important to ensure the person is monitored for recurrence of symptoms due to naloxone wearing off after this time, particularly if long-acting or extended-release opioids are involved.^13,14,24 Any individual receiving naloxone outside hospital requires assistance by emergency services and assessment and monitoring in hospital.²⁴ Patients should not drive/operate machinery for at least 3 days after discharge.8 Further opioids use should be avoided for at least 2 hours after administration.²⁵
• Naloxone should be kept in a place easily accessible in an emergency, and a minimum of two doses available in case a second dose is needed before emergency services arrive. Expiry dates should be checked regularly.¹³
• Discuss potential adverse effects. 
• Provide written information, such as a CMI and product-specific information which explains any relevant preparation involved and administration instructions.¹³
• Discuss available support services or medical advice if appropriate.¹³

For more information and guidance on counselling and supply of naloxone, refer to the Australian Pharmaceutical Formulary and Handbook’s Naloxone for Opioid Overdose non-prescription medicine guide.

How to use naloxone 

There are certain steps that should be followed if a person displays signs of opioid toxicity or overdose in the community. 

1. Call 000 immediately. Advise the ambulance that it is an opioid overdose (or one is suspected).²⁶

2. Administer naloxone (400 microgram IM or 1.8 mg intranasally). 

Intranasal spray (Nyxoid) 

• Naloxone nasal spray contains 2.2 mg naloxone hydrochloride dihydrate (equivalent to 1.8 mg naloxone) in 0.1 mL of solution. Each pack contains two devices.²⁷
• Lay patient on their back, supporting the back of the neck and allowing the head to tilt back. If the nose is blocked, clear the obstruction first.²⁷
• Do not prime the spray before use.²⁷
• Administer ONE spray into ONE nostril by pressing firmly on the plunger (with your thumb on the bottom of the plunger and your first and middle fingers on either side of the nozzle) until it clicks.²⁷
• If the person is not conscious or breathing easily after 2–3 minutes, another dose can be given using a NEW nasal spray into the other nostril.^13,27 Repeat doses can be given every 2–3 minutes if needed until ambulance assistance arrives.²⁷

Injectable naloxone 

• Ampoules (Juno or DBL) – Naloxone ampoules (400 microgram/mL, 1 mL ampoule) are packaged in a pack of five. IM administration is used in the community setting. A 400 microgram dose (1 mL) needs to be drawn into a syringe, requiring a separate supply of needles and syringes, as well as familiarity with this procedure. For more information refer to the Community Overdose Prevention Education program’s Opioid Overdose Response Plan – Ampoules (www.penington.org.au/ wp-content/uploads/2022/09/ COPEampoulesSep2022.pdf). 
• Pre-filled syringe (Prenoxad) – Available as a 2 mL multi-dose syringe containing 1 mg/mL naloxone. A total of five doses can be administered from one syringe, with the same syringe not shared between people due to the risk of blood-borne viruses, unless absolutely necessary.²⁸ Two needles are provided, one of which needs to be attached to the syringe prior to administration (the spare is in case of damage or contamination of the first).²⁸ The initial dose of 400 microgram is 0.4 mL, which is to the first (or next for subsequent doses) black line on the syringe.²⁸ For more information, refer to Community Overdose Prevention Education program’s Opioid Overdose Response Plan – Naloxone Pre-filled Syringe (Prenoxad) (www.penington.org.au/ wp-content/uploads/2022/09/ COPEPrenoxadSep2022.pdf). 
• Once the dose from the ampoule or pre-filled syringe is prepared for use as per product-specific instructions, the 400 microgram dose is injected IM into the upper arm or outer thigh at a 90 degree angle.^25,28
• The dose may be repeated every 2–3 minutes if needed.^25,28

3. If the person’s heart is beating but they are not breathing, apply rescue breathing if trained or comfortable with this.^13,29

4. If no signs of life, start CPR if trained and comfortable doing so.¹³

5. If the person is conscious or breathing normally, place them in the recovery position and keep their airway open and clear (if they are pregnant, place them on their left side).¹³

6. Ensure you stay with the person and observe them until medical assistance arrives.¹³

Potential adverse effects 

Naloxone has minimal adverse effects when used in a person who has not had opioids. A person dependent on opioids may experience signs and symptoms of acute opioid withdrawal (e.g. anxiety, tachycardia, confusion, sweating); however, this is rare with the doses used in the community.^13,29

Other potential signs of withdrawal include vomiting, diarrhoea and muscle pain. In mild cases, an explanation of the situation and a supportive, non-judgemental approach can provide reassurance. 

Patient follow-up 

Not all people who use opioids will be willing or able to commit to treatment for opioid dependence immediately following an overdose. It is critical to remain supportive and non-judgemental, supply information where possible, and ensure access to take-home naloxone and safe injecting equipment if needed. 

Each state has services available to facilitate access to counselling, withdrawal and rehabilitation programs, and pharmacotherapy programs available from community pharmacies. The national Alcohol and Drug Information Service (1800 250 015) can provide free and confidential advice and will automatically connect with the relevant service in the caller’s state or territory.³⁰ Those who have experienced toxicity from prescribed opioids in the context of pain management may benefit from referral to an outpatient pain service via their general practitioner.

Conclusion

There are over 1,000 drug-induced deaths involving opioids each year in Australia.¹ Naloxone is safe and effective and was estimated to save up to three lives per day during the Australian Government’s Take Home Naloxone pilot program, and is expected to save thousands more in the future. By having respectful conversations with people who use opioids and their peers, family and other people who may witness opioid overdose or adverse reaction, pharmacists can have a significant impact on reducing the number of lives lost.

Key Points

• Naloxone is an opioid antagonist that rapidly reverses lifethreatening respiratory depression and other effects associated with opioid toxicity. 
• Naloxone is now available free, without a prescription, from participating pharmacies Australiawide, to those who may experience or may witness an opioid overdose or adverse reaction. Individuals are not required to produce identification to be provided a supply. 
• Pharmacists should identify people who may benefit, and discuss naloxone. Pharmacists must ensure they follow program guidelines and provide appropriate counselling on naloxone and opioid overdose management. 
• Pharmacies wanting more information about the THN program, including how to participate, should refer to the PPA website: www.ppaonline.com. au/take-home-naloxone.

If you do get an enrolment error, please click here

Further Resources 

Australian Pharmaceutical Formulary and Handbook’s ‘Naloxone for opioid overdose’ Non-prescription medicine guide.

Resources for pharmacists on how to have conversations with patients about naloxone for opioid overdose are available at: www.monash.edu/medicine/ehcs/marc/research/current/opioid-safety

Resources for patients and third parties about naloxone and how to administer it are available at: www.penington.org.au/workforce-development/naloxone-training/ and www.monash.edu/medicine/ehcs/marc/research/current/opioid-safety.

Opioid overdose response plans for naloxone nasal spray and injection (including product specific preparation instructions) are available to download at www.penington.org.au/workforce-development/naloxone-training/ (under the heading COPE resources).

Turning point resources including patient and pharmacist information: www.turningpoint.org.au/research/engage/naloxone-project

References

1.   Penington Institute. Australia’s Annual Overdose Report. 2022. At: https://www.penington.org.au/overdose/overdose-projects-campaigns/australias-annual-overdose-report/
2. Australian Government Department of Health and Aged Care. About the take home naloxone program. 2023. At: https://www.health.gov.au/our-work/take-home-naloxone-program/about-the-take-home-naloxone-program
3. Stoové MA, Dietze PM, Jolley D. Overdose deaths following previous non-fatal heroin overdose: Record linkage of ambulance attendance and death registry data: Overdose mortality following heroin overdose. Drug and Alcohol Review. 2009 Feb 25;28(4):347–52.
4. Hill PL, Stoove M, Agius PA et al. Mortality in the SuperMIX cohort of people who inject drugs in Melbourne, Australia: a prospective observational study. Addiction.2022. 117(12);3091–3098.
5. Snyder B. Revisiting old friends: update on opioid pharmacology. Aust Prescr. 2014 Apr 1;37(2):56–60
6. Bachmutsky I, Wei XP, Kish E et al. Opioids depress breathing through two small brainstem sites. eLife sciences. Epub 2020, Mar 17.
7. Williams JT, Ingram SL, Henderson G, Chavkin C, von Zastrow M, Schulz S, et al. Regulation of µ -Opioid Receptors: Desensitization, Phosphorylation, Internalization, and Tolerance. Dolphin AC, editor. Pharmacol Rev. 2013 Jan;65(1):223–54
8. Opioid poisoning: general management. In: Therapeutic Guidelines. Melbourne; 2020. 
9. Boyer E. Management of Opioid Analgesic Overdose. N Engl J Med 2012. Epub 2012, Jul 12.
10. Harm Reduction Victoria. Signs of Opioid Overdose. 2017. At: https://www.hrvic.org.au/_files/ugd/ebb8bf_fe18e39d2e8f4e0186cffe6de6f25884.pdf
11. Naloxone (Nyxoid) nasal spray product information. Mundipharma Australia Pty Ltd; 2019. https://nyxoid.com.au/wp-content/uploads/2022/08/mfpnyxoi31220-clean.pdf 
12. Alcohol and Drug Foundation. Fentanyl. 2023. At: https://adf.org.au/drug-facts/fentanyl/
13. Sansom LN, ed. Australian pharmaceutical formulary and handbook. 2023.Non-prescription medicine treatment guideline [updated 2022 Oct 12]. At: http://apf.psa.org.au/non-prescription-medicine-guides/naloxone-opioid-overdose
14. Alcohol and Drug Foundation. Naloxone. 2022. At: https://adf.org.au/drug-facts/naloxone/
15. Blandthorn J, Bowman E, Leung L, Bonomo Y, Dietze P. Managing opioid overdose in pregnancy with take-home naloxone. Aust N Z J Obstet Gynaecol. 2018 Aug;58(4):460–2 
16. Australian Government Department of Health and Aged Care. Evaluation of the Pharmaceutical Benefits Scheme subsidised take home naloxone pilot. 2022. At: https://www.health.gov.au/resources/publications/evaluation-of-the-pharmaceutical-benefits-scheme-subsidised-take-home-naloxone-pilot 
17. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain—United States, 2016. JAMA. 2016 Apr 19;315(15):1624
18. Pharmaceutical Benefits Advisory Committee. Public Summary Document (March 2019 PBAC Meeting). 2019. At: https://www.pbs.gov.au/industry/listing/elements/pbac-meetings/psd/2019-03/files/naloxone-psd-march-2019.pdf 
19. Pharmacy Programs Administrator. Take Home Naloxone Program. 2022. At: https://www.ppaonline.com.au/take-home-naloxone
20. NSW Health. Take home naloxone program. 2022. At: https://www.health.nsw.gov.au/aod/programs/Pages/naloxone.aspx 
21. Fomiatti R, Farrugia A, Strang J et al. Addiction stigma and the production of impediments to take-home naloxone uptake. Health. 2022;26(2):139–161
22. International Network of People Who Use Drugs. Stigmatising People Who Use Drugs. 2014. At: https://www.unodc.org/documents/ungass2016/Contributions/Civil/INPUD/DUPI-Stigmatising_People_who_Use_Drugs-Web.pdf 
23. Wilson H. How stigmatising language affects people in Australia who use tobacco, alcohol and other drugs. Aust J Gen Pract. 2020 Mar 1;49(3):155–8.
24. Opioid poisoning: advice for first responders in the community or primary healthcare setting. In: Therapeutic Guidelines. Melbourne, 2020. 
25. COPE Penington Institute. Opioid Overdose Response Plan – naloxone pre-filled syringe (Prenoxad). 2022. At: https://www.penington.org.au/wp-content/uploads/2022/09/COPEPrenoxadSep2022.pdf
26. Harm Reduction Victoria. Act in an opioid overdose. 2017. At: https://www.hrvic.org.au/_files/ugd/ebb8bf_9c38c7e8687d4d0681f85ec2eccba2b2.pdf 
27. NPS MedicineWise. Nyxoid. 2018. At: https://www.nps.org.au/medicine-finder/nyxoid
28. Martindale Pharma. Prenoxad Package Leaflet. 2018. Available from: https://www.phebra.com/wp-content/uploads/2017/01/Prenoxad-PIL-March-2018.pdf
29. The Society of Hospital Pharmacists of Australia. Take-home naloxone in Australian hospitals. At: https://shpa.org.au/publicassets/52d5a1ee-de53-ec11-80dd-005056be03d0/thn_practice_update.pdf
30. Australian Government Department of Health and Aged Care. Drug Help – How to find help 2022. At: https://www.health.gov.au/our-work/drug-help/how-to-find-help

ALICE NORVILL (she/her) BSc, BPharm (Hons) is a pharmacist at the Victorian Poisons Information Centre, a service that provides toxicology advice to health professionals and members of the public. She has a background in both hospital and community pharmacy and has been involved with several harm-reduction organisations for many years.

ACKNOWLEDGEMENTS

PROFESSOR SUZANNE NIELSEN (she/her) BPharm, BPharmSc (Hons), PhD, MPS is a member of the National Naloxone Reference Group.

PROFESSOR PAUL M. DIETZE (he/him) BSc (Hons), PhD is the convenor and chair of the National Naloxone Reference Group.

OUR REVIEWER

SHANI PICKERING (she/her) BPharm, MPS, AACPA is a PSA Professional Practice Pharmacist