Harm reduction experts know that naloxone isn't the single solution to the opioid overdose crisis.
“Naloxone isn't the end-all-be-all,” said Nabarun Dasgupta, MPH, PhD, an epidemiologist at the University of North Carolina at Chapel Hill. “We need prevention, we need treatment, we need all sorts of services, but when the overdose death rate is increasing at the pace that it has been, we have to have more emergency antidote available until there are no more overdose deaths.”
According to the latest figures from CDC, reduced access to addiction treatment and services combined with fentanyl contaminating drug supplies resulted in an estimated 100,000 fatal overdoses in 2020 alone.
Adding to the crisis is the lack of naloxone in the hands of those who need it most. CDC estimates that only one naloxone prescription is dispensed for every 70 high-dose opioid prescriptions nationwide. For those who are at the highest risk of an overdose—such as those using illicit drugs—the ratio of naloxone to opioids distributed remains unknown.
Dasgupta works with an organization called Remedy Alliance/For The People. They order and distribute naloxone to harm reduction groups through a unique arrangement, which was formalized this August 2022. Injectable naloxone is manufactured exclusively for Remedy Alliance at a discount and then the Remedy Alliance team processes orders and ships naloxone directly to harm reduction groups.
Many harm reduction programs have historically had difficulty acquiring naloxone. Additionally, these groups as well as many nongovernmental groups and community health centers, have to use their own limited budgets to purchase naloxone at cost or rely on mutual aid networks.
“Right now, there are standing orders allowing pharmacy distribution of naloxone or layperson distribution,” said Dasgupta. “Where those laws fall short is they don't cover bulk purchasing. State laws that have been passed are all dealing within state law in pharmacy practice more or less, but in order to even get the naloxone, you are dealing with interstate commerce and federal regulations because it's the industry that is being regulated and not the boards of pharmacy.”
Efforts from the Remedy Alliance team members reached all the way to FDA and other federal agencies, who agreed to waive the regulations for bulk purchasing through an exception in the federal Drug Supply Chain Security Act (DSCSA).
In a formal announcement about the DSCSA exemption, FDA said they were aware of the contributing factors “to be the current availability of approved naloxone products only as prescription drugs and certain requirements under the [DSCSA] for distribution of FDA-approved prescription drug products, e.g., being an ‘authorized’ trading partner.”
Through the exemption, FDA is advocating for more naloxone to be widely available and accessible in order to reduce opioid overdose deaths.
“Now we can have centralized distribution,” said Jeffrey Bratberg, PharmD, FAPhA, clinical professor at the University of Rhode Island College of Pharmacy. “Anyone like [Remedy Alliance] can do this.”
Bratberg believes it's crucial to expand naloxone access to community programs because they can reach the individuals who face stigma and are normally excluded from health care systems and pharmacy-based naloxone access. They are also the people who are most likely to use naloxone to reverse a witnessed opioid overdose.
Dasgupta said the impact of this new distribution model through the DSCSA exemption has been “immediate and amazing.”
“We've been operating under this naloxone scarcity mentality for decades, that this is something that's been locked up, something that's expensive, something that's precious, and we need to move to a mentality of naloxone abundance,” said Dasgupta. “The only way to do that is with cheap naloxone.” Remedy Alliance has affordable naloxone available.
“The nasal spray is great, but when it costs $50 for a box whereas ours costs a couple bucks [for an injectable], that perpetuates the mentality,” he said.
Pharmacy and community access
Naloxone access laws have now been passed in every U.S. state with the goal of making naloxone available to those at risk of an opioid overdose as well as bystanders who may encounter a person in an overdose situation.
To date, all states give pharmacists the authority to dispense naloxone with a prescription, either through statewide protocols, standing orders, or direct prescriptive authority.
However, naloxone still appears difficult for individuals to obtain in the community, especially in pharmacies.
A recent study from July 2022 published in the Journal of the American Pharmacists Association (JAPhA) found that many barriers still remain that make it more difficult to obtain naloxone from a community pharmacy.
“One of the key findings of the study was that naloxone accessibility seems to be much more limited from independent pharmacies than chain pharmacies,” said lead author Kirk Evoy, PharmD, BCACP, a clinical assistant professor at the University of Texas at Austin College of Pharmacy.
In the pooled data analyzing 30 studies, the research team found that naloxone was immediately accessible without a prescription from 64% of the chain pharmacies versus only 20% of the independent pharmacies.
“It was also interesting that almost all the pharmacies stocking naloxone had the nasal spray available but very few stocked any other formulations,” said Evoy. “This is particularly important for patients who are underinsured or who have financial limitations, as the nasal spray cost generally around $120–150 without insurance coverage versus $20–50 for intramuscular injection formulations.”
According to CDC, 71% of Medicare prescriptions, compared to 42% of commercial insurance carriers, require copayments upwards of $80 for naloxone.
Evoy said there also seem to be many opportunities to address potentially problematic misunderstandings regarding naloxone access laws among pharmacists, such as thinking that they cannot bill insurance companies when dispensing naloxone without a prescription, that naloxone access laws preclude dispensing to adolescents, or that increasing naloxone access could lead to more harmful drug use behaviors.
“With opioid overdoses continuing to cause record numbers of fatalities each year, it is crucial that all health care providers, including pharmacists, do all they can to reduce overdose risk. One key is making sure that naloxone is available as soon as possible when it is needed,” said Evoy.
Naloxone should be available in all the right places, too.
“It's all hands on deck,” said Bratberg. It should be available in pharmacies, mental health clinics, primary care clinics, and mental health clinics—even in vending machines, according to Bratberg. In Bratberg's home state of Rhode Island, vending machines distribute naloxone, harm reduction supplies, and even personal hygiene kits without stigma and at no cost to the recipient, according to Bratberg. The machines and supplies are paid for through grants.
In July 2022, FDA granted the nonprofit pharmaceutical company Harm Reduction Therapeutics fast track designation for their OTC naloxone nasal spray, RiVive (3.0 mg naloxone). The product is currently in development and is expected to be launched in early 2024.
Harm reduction experts have been advocating for an OTC intranasal naloxone formulation for years. Naloxone meets all FDA criteria to become an OTC product: The drug's benefits outweigh its risks; it treats a condition that can be identified without a medical professional's guidance; it has a low misuse potential; and the instructions are understandable by a layperson.
But OTC status should come with some caveats, according to Bratberg. A main concern—once again—is cost.
Bratberg said OTC naloxone could mean individuals would have to pay for naloxone out of pocket when they may have previously relied on insurance to cover or lower the cost. But some insurance companies may choose not to include OTC naloxone formulations on their insurance formularies.
According to an NIH paper published online February 15, 2021, that Evoy and colleagues wrote, federal- or state-level legislation could mandate insurance coverage for OTC naloxone formulations. Additionally, laws in certain states such as New York and Rhode Island that already require insurance coverage for naloxone, could be extended to cover OTC as well as prescription versions of the medication.
It's also most likely that not all formulations of naloxone will transition to OTC status, the authors of the paper point out.
“If an OTC transition occurs, educational outreach and funding for clinical innovations will continue to be crucial given the important role of health professionals in recommending naloxone to people at risk for experiencing or witnessing an [opioid-related overdose],” Evoy and colleagues wrote.
To learn more about harm reduction, check out the January/February 2023 issue of JAPhA.
What is harm reduction?
According to the Substance Abuse and Mental Health Services Administration (SAMHSA), harm reduction is an “approach that emphasizes engaging directly with people who use drugs to prevent overdose and infectious disease transmission, improve the physical, mental, and social wellbeing of those served, and offer low-threshold options for accessing substance use disorder treatment and other health care services.” “Harm reduction is defined as celebrating any positive change that the individual wants to make and being there to support that,” said Nabarun Dasgupta, MPH, PhD, an epidemiologist at the University of North Carolina at Chapel Hill. “If that means using a little bit less tomorrow, great, if that's what they want. If it means that they want to step away from opioids in their lives all together, that's great, too,” he said. Harm reduction is not a defined set of interventions either, even though there are particular interventions that go with it, according to Dasgupta. SAMHSA has worked on defining harm reduction for the United States population and will release a toolkit soon. Visit SAMHSA's website at www.samhsa.gov/find-help/harm-reduction to find out more.
Fentanyl test strips in harm reduction services
The deaths of three “high-achieving” New Yorkers made news headlines last year. All three individuals were found dead after purchasing cocaine laced with fentanyl, supposedly a result of a scheme to lace cocaine with fentanyl to make it more addictive. Stories like these seem to exemplify the issue of how deadly and prevalent fentanyl is within the drug supply. Fentanyl is increasingly being laced with other drugs—not just illicit opioids. Fentanyl test strips have been around for years, but they have been criticized widely and are still illegal in many states. Some lawmakers argue they facilitate drug use. However, according to Kelly Gable, PharmD, BCPP, they have a place in harm reduction services. “Where they are most valuable now is when the drug is not an [opioid] product,” said Gable who is from Southern Illinois University Edwardsville School of Pharmacy. “Fentanyl is in everything.” Fentanyl test strips can detect the presence of fentanyl in heroin, methamphe- tamine, cocaine, and other drugs. “Fentanyl testing strips need to be accessible in any space where people can get other harm reduction things like naloxone,” said Gable. “And they need to be free or low-cost.” Gable would like to see them more widely available at syringe exchanges, even pharmacies. “This is valuable tool in harm reduction space. We need more out there,” said Gable. Gable and a research team conducted a study, published online September 28, 2022, in JAPhA, to assess knowledge and understanding of illicit fentanyl and the motivation to use fentanyl test strips to prevent an overdose. Responses were collected from those receiving residential- or office-based substance use treatment services. The researchers found that many respondents lacked understanding of how to use fentanyl test strips for harm reduction. “They can serve as an opportunity to talk to clients about safe use,” Gable said. “It starts the conversation and is an important educational piece.”