Injectable Naloxone: the wave of the future…and the past
No currently available naloxone product is perfect. Until a naloxone product is developed, packaged, made affordable and accessible to people who use drugs, with input from people who use drugs–none will be.
Naloxone is also just one piece of the puzzle, it is not a solution. It is a band-aid on an open wound that the drug war has created and continues to exacerbate. The unregulated and dangerous drug supply–a direct result of prohibition, US imperialism and the racist war on drugs–will not be fixed with naloxone. We need systemic change, resources and innovative solutions.
This page is a condensed version of the guide: Injectable Naloxone: the wave of the future...and the past.
Read on if you are:
- Introducing choice of product to your participants or responding to demand for injectable naloxone
- Struggling to meet demand and scale-up to saturation with more expensive nasal products
- Exploring the purchase of low-cost generic naloxone for higher volume distribution
Remedy Alliance/For the People provides access to large volumes of low-cost and free naloxone to harm reduction programs, but does this within the context of a broader call for systemic change that includes but is not limited to the following:
Immediate implementation of safe supply
Expansion of accessible, advanced drug-checking technologies
An end to the racist war on drugs and mass incarceration of people who use and sell drugs
Robust low-threshold funding and resource allocation to harm reduction and mutual aid projects who are providing access to life-saving material resources to people who use drugs
Support for innovative supply distribution strategies such as mail-order, vending machine and peer-based models that get material resources into the hands of people who do not have access to traditional brick and mortar programs
Injectable naloxone basics:
The generic injectable naloxone vials that are distributed by harm reduction programs are primarily made by Pfizer pharmaceuticals (orange caps, left), Hikma pharmaceuticals (purple caps, middle), Somerset (blue caps, right), Aurobindo (not pictured) or other generic manufacturers.
The vials of naloxone most commonly distributed are 0.4mg/1ml, which means there is 0.4mg of the drug naloxone suspended in 1ml of fluid. For reference, this is 1/10th the amount of drug in nasal Narcan and generics by Teva, Sandoz and Padagis, which contain 4mgs of the drug in 0.1ml of fluid.
Naloxone vials for injection do not contain the equivalent amount of the drug as in the nasal devices.
|Comparison to injectable
|Narcan & generics by Teva, Sandoz and Padagis
|10 vials of 0.4mg injectable naloxone
|20 vials of 0.4mg injectable naloxone
|12.5 vials of 0.4mg injectable naloxone
These equivalents are simply measurement equivalents, because route of administration matters when talking about naloxone–so one 4mg nasal spray is not truly the equivalent of injecting someone with 10 vials of naloxone because the drug is absorbed differently depending on the route of administration. However, with the Zimhi product, since it is also an intramuscular injection, the 5mgs is the equivalent to the amount of naloxone in 12.5 vials of naloxone since it has the same route of administration.
0.4mg/1ml naloxone is a standard dose to begin the overdose reversal process, but it is important to administer the whole dose–please do not “microdose” injectable naloxone by injecting only a quarter or half of the vial, this amount of drug (0.1mg or 0.2mg) is not likely enough naloxone to successfully reverse an overdose.
Learn more about the history of Naloxone access
Generic intramuscular 0.4mg/1ml naloxone is effective in reversing opioid overdoses– including fentanyl overdoses.
One common misunderstanding about the administration of naloxone is that a higher dose or administering multiple doses in quick succession makes the naloxone work faster or that the overdose reversal was only successful based on the number of doses that were reportedly used. This misunderstanding is exploited by manufacturers of higher-dose naloxone products.
All formulations and potencies of naloxone take 1-3 minutes (average) to begin to take effect–sometimes longer–and any form of naloxone may possibly require a subsequent dose after the first few minutes, depending on the overdose.
If you give 4 doses of nasal NarcanⓇ (16 mgs) in rapid succession during an overdose, it does not make it work any faster than if you give one dose of nasal NarcanⓇ (4mg) or one dose of injectable naloxone (0.4mg), wait, perform rescue breathing, and administer a second dose if needed after several minutes.
Increasingly powerful opioid antagonists are not necessary
2022, The International journal on drug policy
Intranasal and Intramuscular Naloxone for Opioid Overdose in the Pre-Hospital Setting: A Review of Comparative Clinical and Cost-Effectiveness, and Guidelines
2017, CADTH Rapid Respone Report
Bigger doses cause worse withdrawal symptoms
When the naloxone reaches peak concentration (approximately 30 mins for 4mg nasal and 25 mins for IM) an opioid dependent person may feel varying intensity of withdrawal symptoms depending on the quantity of naloxone administered.
The severity of withdrawal symptoms matters for people who use drugs who are dependent on opioids and people taking opioids for chronic pain management. Extreme withdrawal experiences are potentially dangerous, painful and traumatizing. It can result in negative feelings towards naloxone and people who administered it, or result in more concealment of drug use to avoid having naloxone administered.
The introduction of an 8 mg IN naloxone product and the potential future introduction of a similarly potent nalmefene product with longer duration of action could plausibly lead some people who use opioids to avoid carrying it.
Comparison of rates of opioid withdrawal symptoms and reversal of opioid toxicity in patients treated with two naloxone dosing regimens: a retrospective cohort study
2021, Clinical toxicology (Philadelphia, Pa.)
Naloxone–does over-antagonism matter? Evidence of iatrogenic harm after emergency treatment of heroin/opioid overdose.
2015, Addiction (Abingdon, England)
Nobody wants to be Narcan'd: A pilot qualitative analysis of drug users’ perspectives on naloxone.
2021, The western journal of emergency medicine
Reasons people who use opioids do not accept or carry no-cost naloxone: Qualitative interview study.
2020, JMIR formative research
All forms of naloxone may take longer/be less effective with poly-drug overdoses.
Complicating factors in overdose events that can impact the efficacy of any form of naloxone are the addition of other drugs, especially benzodiazepines, alcohol or some substances that are now more frequently found in the street fentanyl supply, like xylazine.
Naloxone has always had its work cut out for it in poly-substance overdose events, especially ones that contain benzodiazepines. It is common for responders to report administering multiple doses of naloxone along with requiring airway management and rescue breathing–a crucial component to any overdose reversal, but especially when the response time is longer and it is more difficult to revive someone.
All about syringes in IM naloxone kits
Include the right size
The syringes included in an IM naloxone kit should be between 1’-1.5” long, hold between 1-3ml of liquid and be at least 25g-21g. The IM syringes should be a large enough gauge to go through clothing, and long enough to reach through the skin and fat layers to the muscle layer in any sized body.
Looking for ways to source IM naloxone syringes? Check out our partners.
Syringes - paraphernalia or medical device?
Legally speaking, the syringes included in an injectable naloxone kit are the prescribed devices needed to administer a medication, and therefore are exempted from laws prohibiting “paraphernalia to inject illegal drugs”—they fall in the same legal category as the syringes needed to inject insulin, IVF or HRT.
Unfortunately, law enforcement can be unaware or unwilling to recognize this difference. Possessing drugs, syringes, other paraphernalia and even nasal or injectable naloxone for aiding another person in distress puts people at great risk of bodily harm or death at the hands of law enforcement - a danger dispropotionalty carried by people who use drugs, especially people who use drugs who are Black, Indigenous, Latinx, sex workers, trans and gender non-conforming.
The problem of syringe scarcity
Many places in the US do not have access to syringe services programs or pharmacies that are willing and able to sell syringes without a prescription. In these areas, some might use the included IM syringes to inject other drugs in a moment of no other option, leaving the kit incomplete in the event the naloxone is needed.
If you are distributing injectable naloxone to people who use drugs in an environment where there is inadequate or zero access to other harm reduction services, it is important to advocate for expansion of harm reduction services in tandem with your naloxone distribution, including syringe access. You can also include explicit information on the naloxone kit targeted to law enforcement explaining that the syringes are medical devices for the administration of a life saving medication and not paraphernalia.
This is a syringe scarcity problem, a problem with paraphernalia laws at the state level and/or a misunderstanding of them at the local level, a law enforcement problem, a war on drugs problem, and a problem with inadequate access to harm reduction services in the majority of the US.
Preferences, nasal vs injectable.
Preference for one form of naloxone over another depends entirely on the person, the program, the community experience, familiarity with both forms of naloxone and accessibility of different products. In places where both options are offered, people often have strong preferences for one over the other, or a preference for both for different situations or different drugs or different people.
Ideally, all people who use drugs should have choice, and they should have access to enough naloxone of either or both forms to support peer distribution and have enough on hand for any overdoses they are likely to witness. If you can scale up your distribution to meet this need with one form or the other–that is ideal and that will get closer to saving the most lives. However, if you cannot do this with one form of naloxone–it is highly encouraged to seek out multiple sources and forms of naloxone to ensure that you have an adequate supply.
Benefits and challenges associated with the different available forms of naloxone
|Form/dosage of naloxone:
|0.4mg/1ml intramuscular (IM) naloxone vial and syringe
|• Lowest dose needed to reverse OD
• Least severe withdrawal symptoms
• Higher bioavailability than nasal (nasal is approx 50% bioavailable compared with IM)
• Low or no cost, ability to purchase large volumes to bring to scale
|• Kits require multiple components and assembly
• Syringe scarcity, no harm reduction services access, stigma and paraphernalia laws make carrying injectable med riskier for PWUD
• Requires more training (but still only minutes)
|NarcanⓇ & generics by Teva, Sandoz and Padagis nasal sprays (4mg per dose)
|• No assembly required
• Easy to use with little instruction
• Preferred by some people with no injection experience
• No syringe involved, less stigmatized and easier in areas with strict paraphernalia laws and syringe scarcity
|• High cost per 2 dose box, prohibitive for scaling to saturation and supporting robust peer distribution
• Participant preference for IM
• Frequent reports of more than 2 doses needed to reverse overdose
|KloxxadoⓇ nasal spray (8mg per dose)
|• Could be effective with non-opioid dependent people who are experiencing an overdose
• Pre-packaged and labeled kits
• Easy to use with little instruction
|• High-dose not supported by robust evidence
• Could likely result in severe precipitated withdrawal in opioid dependent people
• High cost per 2 dose box, prohibitive for scaling to saturation and supporting peer distribution
|ZimhiⓇ auto injector (5 mgs)
|• Could be effective with non-opioid dependent people who are experiencing an overdose
• Pre-packaged and labeled kits
• No assembly required
|• Extremely high dose (equivalent of 12.5 vials of 0.4mg naloxone), not supported by robust evidence
• Could likely result in extremely severe precipitated withdrawal in opioid dependent people
• No use reports from opioid dependent people
So WHY increase distribution of injectable naloxone?
As the drug supply becomes increasingly dangerous and unstable and we lose over 100,000 people a year to preventable overdose death–one thing that we know for sure is that nowhere in the US is enough naloxone being distributed, especially directly to people most likely to witness overdoses.
Injectable naloxone is affordable.
Massive resource misallocation in the last few years has resulted in huge volumes of naloxone purchased with federal and state dollars going to law enforcement, prohibitionist anti-drug coalitions and other more “acceptable” organizations who do not provide robust access to people who use drugs nor do they operate within a harm reduction framework.
Harm reduction and mutual aid groups remain under-resourced and are still struggling to get access to the true volumes of naloxone that they need to distribute to their communities. The cost-prohibitive nature of nasal naloxone products and their dominance in the public funding domain has effectively created a volume limit on naloxone distribution and has indirectly resulted in a deeply rooted resource-scarcity mentality.
In order for harm reduction programs to truly be able to scale up distribution towards “saturation,” and needs-based distribution of naloxone, an affordable product must be considered. Currently, the only affordable product is injectable generic naloxone, so it is imperative that resources and attention be directed back to this well-tested resource.
Intramuscular naloxone is easy to use.
The harm reduction community has over 26 years of experiential evidence that injectable naloxone is acceptable and usable in an overdose situation. In the early days of naloxone distribution, programs were primarily focused on getting naloxone to people who inject drugs, so there was a high likelihood that people may already have experience with using syringes and preparing injections.
However, with the rise in overdoses from drugs consumed by smoking, snorting or taken orally, the recipient of naloxone may not have experience using syringes. Similarly, for concerned friends, family, or the general public may be less familiar using an injected product. Nasal naloxone is a good choice for people with no experience administering naloxone or extreme discomfort with the idea of injecting a medication. However, if access to nasal naloxone is limited or unavailable altogether, it has been demonstrated that people will be open to the injectable option with some training and support, rather than carry no naloxone at all.
Additionally, less-stigmatized injectable medicines are extremely common in out-of-hospital settings and a routine part of our healthcare system-–i.e. insulin, In Vitro Fertilization (IVF) treatment or Hormone Replacement Therapies (HRT). Instructing someone with no experience with injectables on how to draw up the naloxone and inject it intramuscularly can also be done in minutes.
Here are some examples of simple instructions on IM naloxone administration from Community Health Project in Los Angeles, CA.
It is legal to distribute injectable naloxone, and injectable naloxone is an FDA-approved product for use in community distribution programs.
There is no prohibition on the distribution of injectable naloxone from any federal agency. The FDA issued a clarifying statement in 2019 that generic “vial and syringe” naloxone was an FDA-approved product for the treatment of overdose reversal. In 2020, SAMHSA even issued a COVID-19-specific guidance that encourages the use of injectable naloxone during an overdose emergency if the responder feels that nasal naloxone administration poses additional COVID risk. Federal funds may be used to purchase injectable naloxone and are used this way in many states.
If you are being told that state and federal funds cannot be used to purchase injectable naloxone, or that community-based naloxone distribution programs are prohibited from distributing injectable naloxone, this is untrue. Please contact us and we can assist in clearing this up.
Distributing IM naloxone does not increase the risk of needlesticks.
There is no evidence that providing people likely to witness an overdose event with injectable naloxone results in an increase in needlestick injuries.
Are there materials and resources available about IM naloxone?
Yes! There are several decades worth. There are stickers and comics and posters and brochures, and videos and animations–all showing how to administer injectable naloxone. However, as with anything in harm reduction practice, the best materials are made by people who use drugs and people in your own community–where you can adapt to your particular needs, experiences and context. We strongly recommend adapting any of the available materials if you can, and if you cannot, try downloading some of the available materials that you like the best and make sure to credit the original artist or program. Keep it simple, accurate, clear and relevant to your community.