“Naloxone is a medication that rapidly reverses the effects of opioid overdose and is the standard treatment for opioid overdose,” the FDA stated in its announcement. “Rextovy is an additional life-saving medication approved by the FDA to reverse an opioid overdose to be sold directly to consumers and contains the same active ingredient as other naloxone nasal sprays. The availability of multiple approved formulations expands access and market availability, encourages competition that may reduce cost, and offers alternative sourcing options.”

The FDA approved Rextovy as a prescription product in March 2023, about two weeks before it approved Narcan, the 4 mg nasal spray manufactured by Emergent BioSolutions and previously available by prescription, as the first OTC naloxone product. In July 2023 the FDA granted its second OTC approval to RiVive, a 3 mg naloxone nasal spray product from Harm Reduction Therapeutics. Shortly after prescription Rextovy entered the market in early 2024, Amphastar announced that it intended to file an application with the FDA to switch the product to OTC.

Each Rextovy nasal spray delivers a dose of naloxone identical to that of Narcan or any other 4 mg intranasal product. The device itself, however, differs from the widely recognizable design used for Narcan and subsequent opioid overdose antidote products including RiVive, Kloxxado, Rezenopy, Opvee and the various 4 mg generic naloxone nasal sprays.

It’s not clear yet what OTC Rextovy’s retail price will be.

Naloxone was originally only accessible to medical professionals rather than the laypeople who are best-positioned to use it. The prescription version of Narcan was approved as the first naloxone nasal spray product in 2015, and remained the only naloxone nasal spray product until the FDA approved Kloxxado in 2021. In practice, state-wide blanket prescriptions authorized public-health entities to distribute Narcan more like an OTC product than a traditional prescription product, but contracts that favored Narcan over cheaper, generic intramuscular naloxone helped keep naloxone unaffordable for many harm reduction distributors and people who use drugs.

Research has shown limited uptake of OTC naloxone, which makes sense because most people who use it can’t afford to buy it retail. Emergent originally priced OTC Narcan at $44.99 for a two-pack, but competition has slowly made OTC and generic naloxone products cheaper as more of them have entered the market. CalRx, for example, offers its own generic naloxone nasal spray to California residents at $19 for a two-pack.

It’s not clear yet what OTC Rextovy’s retail price will be. GoodRx coupons for the prescription version carried at major pharmacy chains like CVS, Walgreens and Walmart appear to list most prices for a two-pack between $50 and $60, depending on the pharmacy and zip code. The highest prices appear to be $72.24 at CVS and Target across all zip codes.

CVS and Walgreens list Rextovy on their respective websites, but at publication time did not appear to stock it. A Walgreens representative contacted about pricing was unable to locate Rextovy in the pharmacy chain’s online inventory.

OTC Narcan began arriving on pharmacy shelves in September 2023. In May 2024 Walgreens unveiled its own OTC naloxone nasal spray product priced at $34.99 for a two-pack, undercutting OTC Narcan—also stocked at Walgreens—by $10 and likely contributing to Emergent quietly lowering Narcan’s public-interest price (available to authorized syringe service programs and other bulk distributors who give it away for free, as opposed to the higher retail price for individual pharmacy customers) around that same time.

In January 2025 Emergent also acquired the sales and marketing rights for Kloxxado. Though in 2023 naloxone products accounted for more than half of Emergent’s sales, those numbers have steadily diminished even after the addition of Kloxxado. Over the course of 2025 Emergent’s net sales from naloxone products dropped 43 percent, a decrease the company has described as driven “primarily by increased competition.”

Image (cropped) via Food and Drug Administration 

The post FDA Approves 4 Mg Rextovy as Third Over-the-Counter Naloxone Product appeared first on Filter.

Rezenopy is manufactured by Summit Biosciences, which obtained FDA approval in April 2024. In March 2025, the company reached a deal with Scienture Holdings, which is now handling the product’s sales and marketing. In January, after Summit obtained a patent protection that will cover Rezenopy until 2041, Scienture formally put the product on the market. While Scienture stated that the initial distribution period would focus on wholesalers, commercial rollout is expected to begin around April.

Earlier in March, Scienture announced that through group purchasing agreements—contracts that represent multiple health care businesses getting a collective discount price—it would be “providing access” to more than 5,000 health care entities. These reportedly include hospitals, clinics, nursing homes, EMS providers and rehab centers.

“Rezenopy addresses a critical public health need with a differentiated, high dosage formulation designed to combat today’s more potent opioids,” Shankar Hariharan, the executive chairman and co-CEO of Scienture, stated in January. “With a sizable and growing naloxone market, strong FDA approval status and additional [intellectual property patent] protection, we believe Scienture is well positioned to drive meaningful impact while building long-term shareholder value.”

Scienture has estimated that the new group purchasing agreements will give Rezenopy the “potential” to reach more than 60 percent of the institutional market. The company’s stock jumped about 30 percent in the days after it announced the agreements.

“This collaboration is not just about expanding our portfolio,” Hariharan stated in 2025, “it’s about making a real difference in the fight against opioid addiction.” 

Rezenopy is the only naloxone nasal spray product with FDA labeling that suggests a maximum dose.

In 2021, Hikma Pharmaceuticals launched the naloxone arms race with its 8-mg naloxone nasal spray Kloxxado. Next came Zimhi, an autoinjector from Adamis Pharmaceuticals that delivers about 4.5 mg of naloxone intramuscularly, meaning it hits the bloodstream more directly. From there the market jumped from naloxone to the higher-risk, poorly evidenced opioid antagonist nalmefene. Opvee, a nalmefene nasal spray product from Indivior Pharmaceuticals, was pushed on law enforcement departments so aggressively that it prompted a New York State attorney general investigation, and was subsequently pulled from marketing. (We probably haven’t seen the last of it, though.)

As the next step was inevitably a nalmefene autoinjector, in 2024 the FDA approved one from Purdue Pharma. Zurnai quietly entered the market in 2025, though it’s not clear to what extent the product has been made available commercially.

During its FDA evaluation process, Rezenopy was compared to Kloxxado and Zimhi and deemed to be about on par in terms of naloxone exposure. However, it is the only naloxone nasal spray product with FDA labeling that suggests a maximum dose—no more than two in a 24-hour period.

“It is specifically designed for patients who often require multiple doses of lower-strength naloxone for stabilization in emergency situations,” Narasimhan Mani, president and co-CEO of Scienture, stated in December 2025.

These patients are mostly law enforcement. Though the claim that higher-potency opioids require higher-dose naloxone products has been a rewarding one for various cops and pharma companies, a 4-mg Narcan spray actually already contains more naloxone than the dose usually required to reverse an overdose. When it seems like an overdose was too strong for one dose of Narcan and only after five—or more—did the person finally respond, that’s very likely because the cop or well-intentioned bystander kept pumping in dose after dose during the two or three minutes it took for the first one to work.

While nasal spray products are widely used by cops, EMTs and hospitals can administer naloxone through IVs. In many harm reduction circles, the gold standard is generic intramuscular naloxone. Non-nasal spray formulations can be titrated and administered in a more humane way to people who’ve developed physical tolerance to opioids. An unnecessarily high dose triggers precipitated withdrawal, an acutely painful phenomenon that can easily lead to someone overdosing again.

It’s doubtful that 5,000 hospitals and clinics and the like are going to begin using Rezenopy, especially in place of any bulk naloxone purchasing agreement they already have. Scienture is carrying forward the tradition that pharma companies have established with these products since Kloxxado—shoving them toward public-facing institutions so as to give the appearance of widespread uptake, to cover the awkward fact that no one actually asked for them.

Image via stopoverdose.maryland.gov

The post Rezenopy, the 10 Mg Naloxone Nasal Spray, Enters the OD Antidote Market appeared first on Filter.

The HOPE Act was introduced in the 2025 legislative session, when it was referred to the House Rules Committee but did not advance. Now it’s moving again, and has been assigned to the Mental Health & Addiction Committee, where it’s calendared for a hearing February 26. 

Tanya Sorrell, chair of the Illinois Harm Reduction & Recovery Coalition, said the group is “very hopeful” that this year the bill could get to a vote in the House.

“This bill will codify harm reduction,” Sorrell told Filter. 

Among other provisions, the bill would create a chief harm reduction officer position within the health department as well as a Harm Reduction Program Board comprising around 20 members. These would be a mix of legislators, people with lived experience and others with health care or research expertise. In a departure from how various harm reduction working groups or advisory committees have been established in other states, there is no requirement to include members of law enforcement.

“While people who use drugs continue to face social stigma,” the bill states, “they still possess the right to receive access to housing, education, economic mobility, mental health care and a range of services to support a better quality of life.”

At the center of the bill is low-barrier housing. For shelters, low-income housing, recovery housing and housing vouchers, the bill stipulates: “Applicants may not be rejected and residents may not be evicted solely based on abstinence-only or sobriety requirements.” Some shelters and other facilities would be required to update their current policies if the bill were enacted, but disruptive behavior would still be considered cause for removal.

“There are a lot of halfway houses that have an abstinence barrier,” Sorrell said. “Let’s focus on harm reduction and low-barrier housing.”

“The stigma and shame that came with ‘Just Say No,’ ‘This Is Your Brain on Drugs,’ unfortunately pushed people away from ever having these discussions.”

“Housing First,” the evidence-based model that doesn’t require abstinence a precondition of housing, has been increasingly targeted by the Trump administration’s funding cuts. Though the bill would not guarantee funding, should funding be available grants would be awarded to community providers for mobile outreach, or “place-based” harm reduction, in high-risk areas.

The bill would direct jails to provide access to medication for opioid use disorder (MOUD) to anyone eligible, including people experiencing withdrawal even if they hadn’t previously been diagnosed with opioid use disorder. It also allows people already receiving MOUD when they were arrested to continue receiving it while in county jail, but would allow jail staff to “defer” provision if a health care provider determined that “continuation of the medication is no longer clinically indicated.” The patient would be entitled to a written and oral explanation of the decision.

The bill would require state prisons and county jails to provide each person being released with naloxone and a referral to a harm reduction provider. Notably, it would also require that naloxone be made accessible to “incarcerated individuals in all prisons and jails.” While a handful of county jails around the country have piloted naloxone access for people in custody, the only prison system to have done so is the California Department of Corrections and Rehabilitation.

Sorrell confirmed that while the logistics of such a model would likely be worked out later, the intent is for naloxone to be made available to people during their incarceration, in addition to providing kits upon re-entry. This would also mean bringing formal overdose-prevention education and training inside prisons and jails.

“There’s misdirection and sadly just pure misinformation, and disinformation, about what harm reduction does,” Sorrell said. “The stigma and shame that came with ‘Just Say No,’ ‘This Is Your Brain on Drugs,’ unfortunately pushed people away from ever having these discussions.”

Correction, March 26: A previous version of this article stated that no United States prison system has made naloxone accessible to people in custody.

Image via County of Los Angeles Public Health

The post Illinois HOPE Act Would “Codify Harm Reduction” and Housing-First appeared first on Filter.

The report evaluates only one strategy for supply reduction: Interdict the supply of illicit opioids. Fentanyl seizures, basically. Authors acknowledge that any benefits (usually reductions in use or perceived “crime,” more so than reductions in overdose) tend to be short-term.

Of the six strategies the report covers in total, four are considered forms of demand reduction. Three of those are related to treatment: Broaden opioid use disorder (OUD) Medicaid coverage, expand access to OUD telehealth services and expand treatment access for people in the criminal-legal system. 

The fourth is to invest in prescription drug monitoring programs, which the CBO previously considered a strategy for supply reduction but is now apparently one of the best-evidenced strategies for demand reduction. The CBO argues that funding and expanding PDMP will decrease the availability of opioid analgesics prescriptions for new patients, which will result in fewer new cases of OUD, which will reduce the rate of overdose deaths. Almost as an afterthought, the agency notes that “benefits of improving PDMP are offset by some amount of substitution from prescription opioids to illegal opioids (such as heroin and illicitly manufactured fentanyl),” but that PDMP only do this “unintentionally.”

The authors used two criteria when selecting which strategies to include in the report: whether they have “considerable Congressional interest, as reflected in legislative actions and proposals,” and whether their outcomes—successful or not—are evidenced by at least six peer-reviewed papers; three correlational studies and three controlled trials or other quasi-experimental design.

CBO confirmed to Filter that the agency could not find six qualifying papers about the effectiveness or ineffectiveness of SSP.

Even without touching safe supply or overdose prevention centers or any research conducted outside the United States, there is more than one harm reduction strategy that meets those criteria. But the only one the CBO saw fit to include was “access to opioid overdose reversal medications.” 

The report states that evidence for the efficacy of syringe service programs (SSP) is insufficient to meet CBO’s standards, but that the limited evidence that does exist is “mixed.” It cites a COVID-19 pandemic-era study arguing that SSP were responsible for increasing overdose deaths in counties that recently authorized them.

CBO confirmed to Filter that the agency is saying it was unable to find six qualifying papers about the effectiveness or ineffectiveness of SSP.

Peer-reviewed journals are as rife with junk science as any other part of the internet, so the evidence for the effectiveness of anything can be mixed if you want it to be. By the same token, you can take something like, say, nalmefene—a naloxone-alternative with an extremely mixed public opinion and almost no evidence base to speak of—and imply it’s the best-evidenced harm reduction tool of all.

Opioid-overdose reversal medications made it into the report based on evidence supporting the efficacy of naloxone access. And while naloxone is what the CBO discusses primarily, the agency also presents this strategy as applying equally to nalmefene, which “works similarly to naloxone and has stronger and more durable effects.” This is true, but less accurate than saying nalmefene works very differently than naloxone and is unnecessarily potent, to the point of increasing overdose risk rather than reducing it.

While SSP are briefly discussed later in the report, as a sort of honorable mention included due to public interest despite the CBO’s apparent failure to find evidence for or against them, they are not discussed in the context of naloxone access at all. There’s a single line referencing SSP as one of the types of organizations that participate in overdose education and naloxone distribution (OEND), and that line is what should have been the focus of a report that will influence how funds are allocated. 

The report perpetuates a lot of myths besides just syringe programs increasing drug use.

Instead of SSP and OEND, the report focuses overwhelmingly on naloxone access via pharmacies, a strategy irrelevant to the overdose crisis at scale because the people best-positioned to respond to overdose don’t buy it from pharmacies. Much of the data cited are a decade old. The section as a whole is oddly skewed toward issues like out-of-pocket costs, the need to expand naloxone access laws and how the switch from prescription-status to over-the-counter will likely increase availability, which in addition to focusing on entirely the wrong thing lends the report a vague time-capsule quality like the authors have become trapped somewhere in late 2023.

The report perpetuates a lot of other myths and mischaracterizations besides just SSP increasing drug use. It presents fentanyl overdose as requiring higher doses of naloxone. It refers to naloxone itself as a medication that “blocks the effects of opioids,” language more associated with opioid vaccines or naltrexone (Vivitrol). After naloxone and nalmefene, naltrexone is the third opioid antagonist for which the CBO could endorse misleading research here, which it does. 

“Naltrexone requires prior detoxification, so it is not used for initial treatment,” the report states. “Once detoxification is complete, naltrexone is about as effective as buprenorphine.”

This is a false premise. It comes from a National Institute on Drug Abuse study in which 28 percent of participants randomly assigned naltrexone were not able to complete the detox process, compared to 6 percent of participants assigned bupe, and this is the gist of most naltrexone research: If you look at the data without the substantial portion of people who found the onboarding process so unbearable they were unable to get on the medication at all, it works fine.

The outcome of that study was not that the naltrexone patients went off and detoxed, and then successfully started their medication, and then experienced the same results as the bupe patients. The outcome was that six months later—which is really not long enough to draw conclusions about overdose risk reduction for any MOUD, but especially naltrexone—more of the naltrexone patients were using unregulated opioids compared to the bupe patients. But if you take just the patients who did manage to get on naltrexone and compare them to the larger number of patients who managed to get on bupe, you could say the two medications were about equally effective.

Image (cropped) via Congressional Budget Office

The post Feds Compare Strategies for OD Crisis: Reducing Supply, Demand or Harm appeared first on Filter.

A recent study published in Harm Reduction Journal appears to be the first scientific analysis of the naloxone box model. Researchers from HRMI and Facente Consulting found stakeholders “universally” perceived the boxes as a way to democratize naloxone distribution.

“Naloxone is such a safe, easy-to-use, lifesaving tool, and it’s often treated like, ‘Oh, this is a medicine—we have to safeguard it, we have to restrict it,’” co-author Shelley Facente told Filter. “The takeaway from this is just having it in a box—where people can open it and get to it 24/7—works.”

Researchers analyzed data that HRMI staff had been submitting to the state health department, logging how many kits had been taken and from which boxes. They also interviewed 11 people who had played a role in program implementation or accessed the boxes personally. They found that one critical factor in the program’s uptake was 24/7 accessibility—the boxes were placed outside, where the public could still reach them after business hours.

“If it’s 11 pm and they can’t access it, that naloxone isn’t doing any good,” co-author and HRMI founder Pam Lynch told Filter. “I mean, you’re hoping that people are taking kits ahead of time. But we’ve absolutely had situations where people actually drove up to one of our boxes with somebody overdosing in the car and ran up to the box and used the medication on the person in the car.”

A naloxone box outside Short’s Brewing Pull Barn, a “non-traditional” community partner in Elk Rapids, Michigan.

A brand-new HRMI box costs around $500, a fraction of the cost for a naloxone vending machine. But HRMI also got many boxes for free, from local news organizations that no longer needed them.

Compared to vending machines, naloxone boxes also have a much lower barrier to entry in terms of the installation process—they slide easily into the passenger seat or trunk of most cars, which makes them convenient not just to set up, but to relocate.

“While the vending machine model has been really important and really productive … it’s not super accessible,” co-author Katie Burk told Filter. “They’re expensive, they need electricity access, they’re heavy.”

Alongside more traditional venues like harm reduction and social services programs, many “non-traditional” naloxone box placements were initiated by librarians, gas station clerks and small-business owners looking to protect their customers and their neighborhoods. More than 50 of the boxes are stocked by community members, independently of HRMI. The boxes from which people took the most naloxone were the ones outside retail stores; bars and restaurants were popular locations as well.

Lynch told Filter that many business owners felt compelled to implement a naloxone box due to their personal experiences losing loved ones. One local veteran noticed a box stationed at a cannabis dispensary and requested one for her new restaurant.

“She had loved ones who she had done combat with who had overdosed on opioids fatally,” Lynch said. “It was very important to her to place a box outside her newly established restaurant in memory of her colleague and friend who had died.”

Burk pointed out that people often don’t think of overdose prevention as within the scope of work for a librarian, or someone running a cannabis dispensary.

“But I think that these folks, through caring about the issue … really stepped up to the plate and were willing to do the work,” she told Filter.

“Let’s find champions in other areas that have been highly impacted by overdose  … and be a little more intentional about placing boxes there.”

Enthusiasm from community partners was crucial to the HRMI program’s expansion and maintenance. But it also led the geographic distribution of the boxes to reflect interest, rather than need. Some of the counties with the highest rates of overdose deaths still have very few boxes, or none at all. Burk said this shows the importance of HRMI and other organizations seeking out community partners in high-impact areas—rather than waiting for partners to come to them.

“Let’s find champions in other areas that have been highly impacted by overdose and overdose deaths,” she said, “and be a little more intentional about placing boxes there.”

While some interviewees told the researchers that the boxes received initial pushback, they noted that over time the program sparked many productive conversations and changed the minds of community members who had initially been wary or confused. One person who worked at a “non-traditional” box location told the researchers that they’d seen “a lot of success with people in terms of broadening their horizons.”

More harm reduction organizations are beginning to implement the naloxone box model in free clinics, college campuses and other community spaces. With naloxone products increasingly accessible, Facente hopes her team’s research will encourage more people to embrace this low-threshold approach to naloxone distribution—making kits freely available in public spaces, without unnecessary barriers. 

“Naloxone hasn’t been treated that way,” she said, “but there’s really no reason that it can’t be.”

Images via Harm Reduction Michigan

The post Naloxone Boxes: New Strategy Makes OD Antidote Accessible 24/7, for Free appeared first on Filter.

Nalmefene is an opioid antagonist that since 2023 has been presented as a competitive alternative to the better-known naloxone, mainly because its effects last several hours longer. Contrary to baseless propaganda from law enforcement and misleading research from pharmaceutical companies, nalmefene has no proven overdose-reversal advantage compared to naloxone and has been universally condemned by public health experts for potentially increasing risk of overdose, when administered to people with a physical dependence on opioids.

Promotion of Opvee, the only nalmefene overdose reversal product currently on the market, was recently discontinued amid a settlement with the New York State attorney general’s office, which required manufacturer Indivior to “stop making false statements” about nalmefene having “approvals, characteristics, uses, benefits or qualities that it does not have,” particularly with regard to claims that it performs favorably compared to naloxone.

Tharimmune is developing its nalmefene product for the indication of “Temporary Prophylaxis of Respiratory and/or Nervous System Depression in Military Personnel and Chemical Incident Responders Entering and Area Contaminated with High-Potency Opioids.” TH104 is expected to be a dime-sized sublingual film that sticks to the inside of the cheek, takes effect within 30 minutes and lasts for around 24 hours. Like Indivior, Tharimmune is highlighting its product’s “potential superiority” to naloxone.

The FDA has reviewed and concurred with Tharimmune’s quantitative modeling plan for TH104, supporting further development of our lead prophylactic candidate for respiratory depression caused by fentanyl and ultrapotent opioids.

Full release: https://t.co/YXsSdhh3Rm pic.twitter.com/EhP1RKrtkH

— Tharimmune, Inc. (@TharimmuneInc) November 13, 2025

Though Tharimmune announced the news November 13, a Securities and Exchange Commission filing indicates that the company first discussed the additional indication with the FDA in March and had received the positive feedback on its Pre-Investigational NDA by July. Tharimmune is planning to file this NDA before it moves forward with the original TH104 indication for chronic itchiness resulting from primary biliary cholangitis, a degenerative autoimmune disease that attacks the liver.

“The buccal film delivery of TH104 is designed as a non-injectable, rapid absorption and convenient to be self-administered, which may be advantageous for first responders who may be wearing full protective gear,” states the November 13 announcement. “Tharimmune is dedicated to advancing TH104 to provide a potentially effective and patient-friendly treatment as an option for those in need, beginning with its critical role in national security.”

In the tradition of several pharmaceutical companies that came before, Tharimmune is going for language choices that could mean TH104 is intended for routine law-enforcement duties or large-scale terrorist attacks, or both.

Despite the awkward commercial failure of Indivior’s nalmefene-based Opvee, the company still has an active contract with the Biomedical Advanced Research and Development Authority (BARDA) to stockpile the product for use by first responders “in accidental or intentional mass casualty situations” caused by extremely hypothetical “biosecurity threats involving synthetic opioids.” 

Before that, in 2022 the Department of Defense partnered with Kaleo, Inc. to develop a high-dose naloxone product specifically for use by the military, in the event of equally hypothetical situations where use of “high-potency opioids such as fentanyl analogues as a chemical weapon is suspected.”

Tharimmune did not respond to Filter‘s inquiry about what scenarios TH104 was intended for and whether any federal agencies are interested in purchasing the product.

First responders aren’t the only ones with occupational exposure to fentanyl.

“The foundation for the FDA’s alignment on the submission of an NDA without additional clinical trials rests on the extensive existing data related to the approved active ingredient nalmefene,” Tharimmune states on its website. “This includes a comprehensive understanding of its safety profile, established through years of use in approved products, and evidence of its efficacy for opioid overdose.”

On November 11, two days before Tharimmune’s announcement, the American College of Medical Toxicology (ACMT) and American Academy of Clinical Toxicology (AACT) published a position statement focused on passive opioid exposure among first responders. It warns that nalmefene has “limited data regarding its use in fentanyl overdose” and “should not be considered the first-line agent for opioid reversal until more robust data are available.” In 2023 the ACMT and AACT published a position statement focused on nalmefene specifically, describing why it should not be used in place of naloxone.

The FDA did not respond to Filter‘s request for comment.

The new position statement, which is excellent, systematically debunks the myths that fentanyl overdose can result from passive inhalation (breathing in particles of fentanyl that might be swirling in the air) or absorption through the skin or mucous membranes.

It makes clear that fentanyl-based terrorist attacks are “beyond the scope of this document,” but does state that in “exceptional circumstances where there are drug particles or droplets suspended in the air, an N95 respirator” would suffice. It also states that in the “unlikely event of environmental opioid poisoning due to handling fentanyl (or any opioid), naloxone should be administered” only if someone is actually exhibiting symptoms of opioid overdose.

First responders aren’t the only ones with occupational exposure to fentanyl. Drug sellers, drug users, hospital workers, pharmaceutical researchers, forensics scientists, lab technicians, overdose prevention center staff—none of them ever need “sustained prophylaxis” before they can enter a room with fentanyl in it.

The myth that fentanyl and other “ultrapotent opioids” are evolving to the point that a standard dose of naloxone is no match for them only exists because once you sell the public that problem, the FDA will entertain your (potentially) very lucrative solutions. Half a dozen nalmefene or higher-dose naloxone products have been approved in the past four years. To date, there has never been a single confirmed report of intoxication from passive opioid exposure.

Image (cropped) via United States Department of Justice/YouTube

The post Now the FDA Wants Nalmefene to Be a Fentanyl-Exposure “Prophylactic” appeared first on Filter.

After sitting in the Committee on Mental Health, Substance Use and Recovery since February, a joint hearing for MA H2217 has now been scheduled for November 3. The bill would subtly, but meaningfully, modify the section of state law that covers opioid-overdose reversal agents to increase access to Opvee, a nasal spray device that resembles Narcan but is formulated with nalmefene, rather than the better-known opioid antagonist naloxone. Nalmefene has no proven benefits compared to naloxone. But because it lasts several hours longer, it would in some cases introduce unnecessary pain and risk of overdosing again by triggering a syndrome called precipitated withdrawal.

Currently, section 19B of chapter 94C in Massachusetts state law defines “opioid antagonist” as “naloxone or any other drug” approved for opioid overdose reversal by the Food and Drug Administration. Even though naloxone and nalmefene are already the only two drugs that meet that criterion, the proposed legislation would remove the reference to naloxone, making the definition simply “any drug” approved for reversing opioid overdose. The health department would be required to issue a statewide standing order for pharmacists to dispense “all opioid antagonist,” whereas under the current law it simply has the option of issuing one for “an opioid antagonist.”

Though since 2023 some naloxone products have designated over-the-counter medications, rather than prescription medications, states have long relied on blanket prescriptions called “standing orders” to allow bystanders to administer naloxone to someone overdosing.

In September, Opvee manufacturer Indivior Inc. agreed to a settlement with the New York State attorney general’s office after an investigation revealed it had marketed Opvee in violation of state law. New York’s standing order is specific to naloxone—but Indivior led local law enforcement agencies to believe that it could apply to all opioid antagonists.

Around the same time, the company internally informed stakeholders that it would no longer market Opvee at all. Since then, however, senior representatives have continued to publish misleading research claiming that risk of precipitated withdrawal is low and falsely suggesting that nalmefene has benefits that naloxone does not.

The Massachusetts Department of Public Health has so far declined to make the state’s standing order inclusive of nalmefene or higher-dose naloxone products, stating that “these agents are more likely to precipitate withdrawal, which can increase mistrust and foster avoidance of overdose reversal assistance among people who use drugs.” An investigation by the Shoestring and New England Public Media revealed that the Massachusetts Chiefs of Police Association was pushing out free samples of Opvee and asking public officials to “nudge” the health department into revising its position.

A second nalmefene product, an autoinjector developed by Purdue Pharma, is expected to join the market by the end of 2025.

The state is also considering multiple separate bills that govern what happens after someone is administered an opioid antagonist.

The state is also considering multiple separate bills that govern what happens after someone is administered an opioid antagonist.

Under MA H2420, if a law enforcement officer or other first responder “administers an opioid antagonist, as defined in section 19B of chapter 94C, to a person suffering from an apparent drug overdose, such person shall be transported, with or without the person’s consent, by ambulance to a hospital for monitoring, observation and possible treatment.” 

It would authorize law enforcement to restrain the person if they deem it necessary, as well as search the person and “the immediate surroundings” to check for weapons.

Because precipitated withdrawal is a painful and disorienting experience, giving someone an excessive dose of an opioid antagonist risks the person becoming agitated when they regain consciousness. (An appropriate dose of an antagonist, which is easiest to achieve using generic intramuscular naloxone, would simply restore the person’s ability to breathe on their own without even waking them up.)

The state’s “Good Samaritan” overdose law protects overdose victims from possession charges, or parole/probation violations, if law enforcement finds the incriminating evidence while rendering aid. However, that immunity has limits, such as not covering possession of larger quantities.

The bill is currently with the Joint Committee on Public Health.

MA 1042, also currently with the Joint Committee on Health Care Financing, would prohibit any patient “who has suffered an overdose or who required the administration of an opioid antagonist” from being discharged until they meet with a social worker, recovery coach and recovery navigator. The discharge also “shall not be granted unless approved by the judge who issued the order for civil commitment.”

Under MA H2213, after someone is evaluated for substance use disorder, if they’re brought back to an emergency department within the next seven days due to an overdose then “the attending physician may authorize the restraint of such person and apply for the treatment of such person for a three-day period at a facility authorized for such purposes.” That bill is currently with the Joint Committee on Mental Health, Substance Use and Recovery.

Image (cropped) via County of Santa Clara

The post MA Overdose Bills Signal Push Toward Nalmefene, Civil Commitment appeared first on Filter.

In a study published October 22 in medical journal Cureus, authors aimed “to evaluate the prevalence and clinical significance of precipitated withdrawal” associated with intranasal (IN) nalmefene (which by default means Opvee). They reviewed 246 instances of Opvee use and found that only two were linked to precipitated withdrawal. All 246 cases were self-reported to Indivior directly, and all six authors are currently employed by Indivior. 

“‘[S]tandard’ doses of naloxone used in a community setting could result in preventable fatalities when confronted with a potentially lethal dose of a synthetic opioid such as fentanyl,” the authors wrote. “Post-marketing surveillance data suggest that the risk of precipitated withdrawal with IN nalmefene is low in real-world settings. These findings support the continued deployment of IN nalmefene as a life-saving intervention.”

Prolonging the effects of an overdose reversal increases the risk of overdosing again. 

In 2023, the Food and Drug Administration approved Opvee as the first opioid-overdose antidote formulated with nalmefene, rather than the better-known opioid antagonist naloxone. The product was enthusiastically received by local law enforcement departments (and the federal Biomedical Advanced Research and Development Authority). But it was rebuked by harm reduction groups, several health departments and the country’s preeminent toxicology associations, who all warned that deployment of Opvee instead of naloxone products like Narcan would put lives at risk.

The effects of nalmefene last hours longer than those of naloxone, which Indivior has framed as a competitive advantage even though there’s no need for naloxone to last any longer than it does—and prolonging the effects of an overdose reversal actually increases the risk of immediately overdosing again. 

Having an overdose reversed is generally not a painful experience for people who don’t regularly use opioids. But for people who do, an excessive dose of an opioid antagonist triggers an excruciating syndrome called precipitated withdrawal. The longer it lasts, the more likely it is that the person will use more and more opioids trying to relieve the symptoms. 

In early September, Indivior Vice President of North America Medical Affairs Ann Wheeler, who is one of the Cureus study’s six coauthors, told stakeholders that Indivior would no longer promote Opvee. That decision came amid a settlement with the New York State attorney general’s office, in which Indivior agreed that effective September 29 it would “not make any written or oral statement about nalmefene/Opvee that is unfair, false, misleading, deceptive or unconscionable.” The company also agreed to “not represent that nalmefene/Opvee has approvals, characteristics, uses, benefits or qualities that it does not have.”

The settlement is specific to commercial marketing activity within the state of New York.

It isn’t clear how many of the cases without precipitated withdrawal involved people who were ever at risk of precipitated withdrawal.

One of the findings highlighted in the study is that more than one-third of the reported reversals came from Michigan.

“To date, there have been no precipitated withdrawal adverse events reported from Michigan,” the authors wrote. “The absence of reported precipitated withdrawal in this mixed urban and suburban setting suggests a favorable safety profile, especially considering the scrutiny around the risk of precipitated withdrawal for this product.”

It might also suggest that, perhaps, one-third of the study’s data was submitted by the Oakland County Sheriff’s Office. The OCSO, which covers most of the suburbs in the northern Detroit metro area, was the first law enforcement department to start using Opvee back in late 2023.

Naloxone misinformation is so deeply embedded in cop culture that officers systemically conflate opioid overdose with all kinds of things that are not opioid overdose. In addition to not clarifying how many of the 244 cases without precipitated withdrawal involved people who regularly used opioids—versus people who were never at risk for precipitated withdrawal in the first place—the study also doesn’t clarify how many cases were confirmed to involve opioid overdose. Versus just involving deployment of Opvee. Authors did not respond to Filter’s request for comment on various aspects of the study.

Elsewhere in the study they note that their findings are consistent with a recent “independent review by two clinical experts of body camera footage of a first responder administering IN nalmefene to an individual with a suspected opioid overdose … and no evidence of precipitated withdrawal.”

Though not employed by Indivior, both those experts have a financial relationship with the company, including over $10,000 apiece in Opvee-specific consulting fees and travel expenses in late 2024. Filter had also previously reached out to them about that body camera footage review, to ask if the individual had been at risk for precipitated withdrawal; it doesn’t appear that he was.

So for the most part the paper’s approach is a familiar one: Highlight cases where Opvee didn’t cause precipitated withdrawal, using ambiguous language that never confirms or denies there was ever a risk of precipitated withdrawal. But the paper also includes an unconventional claim: Maybe people who use fentanyl regularly actually become immune to precipitated withdrawal.

“[Fentanyl’s] rapid uptake into the central nervous system is followed by a redistribution to peripheral tissues including muscle and adipose. Converging lines of evidence indicate that … redistribution to peripheral tissues creates a reservoir, slowly releasing fentanyl back into the circulation,” the authors wrote. “This sustained fentanyl exposure in chronic users could mitigate the manifestation of severe precipitated withdrawal when a reversal agent is administered.”

The length of time a drug stays detectable in various bodily tissues is relevant for drug-testing, but not for experiencing the effects. Fentanyl’s effects peak pretty quickly. But part of the Opvee marketing playbook was mischaracterizing fentanyl as a long-lasting drug—so long-lasting that overdose symptoms could spontaneously return hours later, by which time naloxone would have worn off. But not nalmefene.

Image (cropped) via National Library of Medicine

The post Indivior Isn’t Done With Opvee, the Overdose Antidote That’s Not Narcan appeared first on Filter.

Though Indivior will no longer “actively market” Opvee, it will continue to manufacture it. Licensed medical providers will be able to prescribe it, and health departments or other public interest groups will be able to order it; they’ll just have to reach out to Indivior rather than the other way around.

On September 30, the Office of New York State Attorney General Letitia James (D) announced that at the beginning of the month, Indivior agreed to a settlement requiring it to “stop making false statements” about its “unauthorized” product. Two days later, the company sent a letter to health care providers and other stakeholders informing them Opvee was no longer being promoted at all.

In the letter, which Filter has reviewed, Indivior Vice President of North America Medical Affairs Ann Wheeler wrote that the discontinuation took effect August 26.

“Indivior has not taken this action due to safety or efficacy issues related to the product,” Wheeler wrote. “Rather, the decision was based on business reasons and shifting our focus to other parts of our business.” 

In recent years, the FDA has approved a handful of naloxone products as over-the-counter medications, but for years Narcan still technically required a prescription. In order to get around this—so that bystanders could legally respond to overdose without waiting for a doctor’s permission—states enacted blanket prescriptions known as “standing orders.” Like many health departments, the New York State Department of Health (NYSDOH) has a standing order authorizing non-medical distribution of naloxone, but only naloxone—not nalmefene. Opvee still requires a traditional prescription. But Indivior didn’t present it that way.

“Despite [the] clear limitation under state law, Indivior marketed and sold the drug as if it were a viable competitor to Narcan,” the OAG stated, “misleading public agencies and undermining established, evidence-based overdose prevention efforts.”

By January 2024, according to the OAG’s investigation, Indivior had pitched Opvee in at least 15 counties across New York, opening dialogues with local officials from sheriffs to commissioners to EMS chiefs.

The investigation centered on Indivior’s dealings with the Broome County Sheriff’s Office (BCSO), which in the spring of 2024 had told the company that, per NYSDOH, nalmefene-based products were not covered by the standing order. In response, Indivior suggested that BCSO “was not barred from writing its own nonpatient-specific standing order for Opvee.”

BCSO bought 300 doses, blithely violating state law in the process, and in a matter of weeks announced the launch of a “fentanyl fighter” Opvee pilot program.

Though only referenced as “business decisions” in the letter to stakeholders, Indivior is looking to offload Opvee.

Nalmefene and naloxone are both opioid antagonists, but nalmefene’s effects last up to 11 hours compared to under two hours for naloxone. Opioid antagonists work on all opioids the same way regardless of their potency, and the longer they remain in someone’s system the more likely the person is to overdose again.

“Public health officials discourage the use of Opvee,” the OAG stated. “Not only does Opvee not improve survival rates or patient outcomes, but its longer duration can also cause severe and … extended withdrawal [that] is painful for patients and puts them at risk of life-threatening conditions for longer than necessary.”

But Indivior, and the various law enforcement departments to have taken up the cause, used nalmefene’s longer half-life to frame it as new cutting-edge technology, and naloxone as weak and outdated.

For example, an Indivior-sponsored paper that purported to address the “lack of published evidence regarding [intranasal nalmefene’s] utilization, namely regarding concerns about its potential for precipitate withdrawal,” described a man who was successfully revived with Opvee and—”notably”— did not experience precipitated withdrawal. Earlier in 2025 when Filter inquired about whether that man had an opioid tolerance that put him at risk for precipitated withdrawal in the first place, authors responded that to their knowledge “he had no previous issues”—which is not the framing that was used in the paper. In a separate study by researchers directly employed by Indivior, nalmefene outperformed naloxone in a lot of impressive-sounding metrics that had little to no bearing on whether someone survives an overdose.

In a fairly damning Assurance of Discontinuance issued by the OAG, effective September 29 Indivior has agreed to not describe Opvee or nalmefene—verbally or in writing—in any way “that is unfair, false, misleading, deceptive or unconscionable,” or that suggests its product “has approvals, characteristics, uses, benefits or qualities that it does not have.”

Though Indivior’s letter to stakeholders didn’t elaborate on the “business decisions,” the company is looking to offload Opvee. Its cash cow is Sublocade, the long-acting injection formulation of buprenorphine, and that’s where it intends to focus its energies going forward. On August 26, the same day it pulled Opvee’s marketing, Indivior filed a Securities and Exchange Commission report outlining a new “Action Agenda” centered on layoffs and consolidations.

“Indivior is exploring strategic alternatives for both OPVEE® and its non-US business,” the report stated. “To the extent the Company is successful in divesting and/or restructuring these assets, further one-time costs and ongoing expense savings may be realized.”

Marketing and promotion was where Opvee made an impact, much more than through use of the actual product.

Despite Opvee’s outsized presence in the media, in 2024 it brought in about $15 million—a little over 1 percent of Indivior’s net revenue. That sum came from two 100,000-unit orders from the United States Biomedical Advancement Research and Development Authority (BARDA). Since August 2024, Indivior has had a federal contract to provide BARDA with an emergency stockpile of Opvee in case of fentanyl nuclear war, or something like that.

That contract remains active, and as of August 19 the government has awarded $52.9 million. It may still award an additional $60.9 million over the next eight years. Indivior did not respond to Filter’s inquiry about the future of the BARDA contract, or whether the company is still offering to pay a portion of its opioid settlements in Opvee units.

Marketing and promotion was where Opvee made an impact, much more than through actual use of the product. Less than two years since the first law enforcement departments got access, the FDA has approved a nalmefene auto-injector from Purdue Pharma and a naloxone nasal spray containing a dose two-and-a-half times bigger than Narcan. Whether or not another company acquires it, Opvee’s legacy will be that it popularized the narrative that naloxone doesn’t cut it anymore. That it wears off too quickly, that it works too slowly, that it only works after multiple extra doses, that ultra-potent naloxone-resistant synthetic opioids are flooding the country. None of which are true. 

Higher-dose naloxone products were already emerging by the time Opvee hit the market. But as the first alternative to naloxone, Opvee became a vehicle for cops to air their frustration over the fact that responding to people who use fentanyl is now such a large part of their jobs, and it validated the mythology that the only reason they haven’t yet won the drug war is because the law denies them access to the resources they need. Rather than because prohibition doesn’t work that way.

Image (cropped) via Broome County, New York

Correction, October 1: This article has been edited to identify the New York State Department of Health, which was originally misnamed as the Department of Health and Mental Hygiene.

The post Opvee, High-Profile Overdose Antidote No One Used, Discontinues Marketing appeared first on Filter.

A new study published in the journal Drug and Alcohol Dependence, which analyzed medical examiner records in rural Minnesota, provides encouraging evidence that these efforts are paying off. From 2022 to 2024, the region’s fatal overdose rate declined by over 40 percent, with Indigenous communities experiencing an especially strong 47 percent decline. White and Black communities saw declines of 35 percent and 21 percent, respectively.

One severe racial disparity, which at one point saw overdose mortality more than 17 times higher among Indigenous residents than among the region’s white residents, has thus decreased. However, Indigenous mortality remained six times higher at the end of 2024. 

Overdose mortality rates by racial group. Graphic used with study authors’ permission. 

The study analyzes 967 overdose death records from 36 Minnesota counties from 2022 through 2024, as reported by the Midwest Medical Examiner’s Office. While limited in geographic scope, it provides a much more up-to-date picture of the overdose crisis than national data.

“We are well into 2025 and still only have provision counts for 2023 nationally,” lead author Dr. Bradley Ray, of RTI International, told Filter. “Many jurisdictions don’t yet have the data to determine if there are reductions.”

In addition to examining overdose rates, Ray and his team also analyzed which substances were most often listed in postmortem toxicology reports. Despite growing national concern about xylazine, the reports contained little evidence of xylazine in the local drug supply. Among substances found to be present—which doesn’t, of course, demonstrate that a particular drug caused a death—fentanyl and methamphetamine dominated, with a few cases involving cocaine or prescription opioids, and nearly no reports of heroin.

“A decrease in [Indigenous] overdose deaths may be reflected in future national data or alternatively could be unique to this region.”

“Based on the data we have examined, xylazine is not all that prevalent up here,” Ray explained. “It may be that rural America does not have xylazine at the levels that people in the urban areas are seeing.”

The study emphasizes that more research is needed to understand whether northern Minnesota’s decline in fatal overdose rates, persistent racial disparities and striking absence of xylazine are representative of rural and tribal communities more broadly. However, these local findings offer important clues as the federal data slowly trickle in.

“Time will tell as those data become more available,” Ray said. “We found a decrease in overdose deaths among American Indian and Alaskan Native people in 2024 that may be reflected in future national data or alternatively could be unique to this region.”

Sue Purchase, founder of Harm Reduction Sisters, which serves many of the communities included in the study, credits these improvements to recent legislative changes that protect harm reduction work. 

In 2023, Minnesota was the first state to completely repeal its drug “paraphernalia” laws, removing many of the legal restrictions against syringe service programs and drug checking initiatives.

“[These laws] really paved the way for tribal nations to support harm reduction in a much more comprehensive way,” Purchase told Filter, adding that opioid settlement dollars also contributed to the feasibility of implementing these newly legalized programs.

However, she also cautioned that the medical examiner data likely underestimate the true disparity, due to how race is recorded.

“If you’re native and don’t have tribal ID on you, they count you as white,” Purchase explained.

“In many ways, we’ve been on a more positive trajectory. But due to, you know, the authoritarian crackdown, we’re going to lose any progress that we have made.”

Regardless of the accuracy of Ray’s figures, the disparity in overdose deaths between white and Indigenous populations remains alarmingly wide, both in Minnesota and throughout the country. To close the gap, Purchase emphasized doubling down on what is known to be effective.

“It’s all the things we always talk about,” she said. “Stigma kills. We have a general lack of housing. We have entrenched racist attitudes and closed minds.”

But this is easier said than done, as she acknowledged. And with federal policy changes negatively transforming the legal landscape for harm reduction—as well as housing, medical insurance and other resources critical to people who use drugs—Purchase worries that the current advances could quickly unravel.

“In many ways, we’ve been on a more positive trajectory,” she explained. “But due to, you know, the authoritarian crackdown, we’re going to lose any progress that we have made.”

With harm reductionists on the defensive nationwide, Purchase emphasized the importance of keeping Minnesota’s relatively progressive state laws intact.

“We really hope to protect those, keep those on the books and prevent further harm,” she said.

Top photograph by Mark Oniffrey via Wikimedia Commons/Creative Commons 4.0

The post Indigenous OD Mortality Plummets in Minnesota, But Disparity Remains appeared first on Filter.