Numerous medications that are now available over-the-counter were once prescription-only, including antihistamines, nicotine replacement therapy, and certain analgesics. These nonprescription switches have benefitted public health efforts by establishing universal access, a prime example being the emergency contraceptive Plan B (levonorgestrel), a safe and effective treatment to prevent unintended pregnancy. The American College of Obstetricians and Gynecologists (ACOG) was one of the first groups to support Plan B’s nonprescription conversion, along with the American Medical Association (AMA) and the American Pharmacists Association (APhA), who have supported it as well. After a protracted legal and ethical siege, the Food and Drug Administration (FDA) made Plan B an over-the-counter medication in August 2006, albeit with age restrictions. Full, unfettered access would not occur until February 2014 when generic levonorgestrel could be sold without a prescription. While unintended pregnancies still occur, emergency contraceptive is available for all women, even if rates of use are heterogeneous.
Contrast this vignette to the current opioid overdose epidemic, now compounded by the COVID-19 pandemic. From May 2019 to May 2020, more than 81,000 overdose deaths occurred in the United States, the highest number yet recorded by the Centers for Disease Control and Prevention. In Rhode Island, at least 384 deaths from opioids occurred in 2020, an increase from 308 fatalities in 2019. The opioid antidote naloxone (Narcan) is a safe, uncontrolled, prescription medication with proven morbidity and mortality benefits—if someone can obtain it and readily have it on hand. Despite policies such as co-prescribing mandates, increased insurance coverage, community outreach funding, and standing orders at pharmacies that permit “behind-the-counter” access, naloxone remains largely unreachable to those who need it the most, similar to Plan B prior to its over-the-counter switch. Professional organizations including the AMA and APhA have recognized this issue, releasing position statements (similar to ones on emergency contraceptives) that approve of over-the-counter naloxone. Bias, pharmacy availability, cost, and structural racism are all difficult barriers to naloxone acquisition. To achieve universal, equitable access to naloxone, we recommend instituting changes to establish an affordable, over-the-counter supply: “Plan N.”
BARRIERS TO NALOXONE ACCESS
Dispenser and recipient biases impede naloxone receipt. In a study of 20 people who use opioids in New York City, bias was the main concern they had about accepting or carrying naloxone. Naloxone is “nearly synonymous with illicit substance use,” especially if the person is carrying the medication in the blue bags that the state of New York uses to distribute free naloxone. People do not want to be identified as drug users, and the connection between saving lives and naloxone is often obscured amongst the general public. On the dispensing side, some pharmacists are afraid of offending their patients if they offer them naloxone, while others feel uncomfortable or unsure on how to broach this difficult subject. Pharmacists have the knowledge of naloxone and opioid use disorder (OUD) but find it challenging to talk to their patients about these topics; some practitioners may even knowingly discriminate against patients with OUD, obviating the development of therapeutic relationships. This same bias may be held by providers as well, further alienating people with OUD from the health care system.
Naloxone availability is extremely variable; it has been found to be inadequately stocked in areas with high overdose rates, minority neighborhoods, and areas with a low average household income. One reason for this lack of availability may be the result of a phenomenon known as “medication deserts,” a term that describes areas where geographic access to pharmacies is severely limited and the stock at these locations may be insufficient to meet patients’ needs. In poorer districts, where people who are unlikely to own cars live, pharmacies have a greater chance of not having medications stocked in comparison to those in more affluent areas. Not only are residents of these areas more likely to be diagnosed with asthma, hypertension, and type 2 diabetes, they may also have to travel farther to simply procure medications for managing these diseases.
Cost is another large hurdle. While generic formulations can reduce the price of medications, expenditures are likely to remain high until adequate competition arises. The most-commonly prescribed Narcan nasal spray formulation has a list price of $150, and even after using drug coupons such as GoodRx, the cost still averages around $125. On the other hand, two generic 0.4 mL vials for intramuscular (IM) injection can be purchased for about $17 on GoodRx. Pharmacy sales, however, have significantly shifted from IM to the intranasal formulation due to its greater ease of administration with the ready-to-use nasal spray and its comparable efficacy. At pharmacies, insurance coverage (and Medicaid expansion) mitigates the issue of cost, but plan limitations continue to plague patients.
The facets of structural racism perpetuate weaker OUD management practices for communities of color, disproportionately increasing the risks of overdose and death for people of color. Emerging data from Philadelphia show that Black Americans experienced more fatal overdoses than their White counterparts during the peak of the COVID-19 pandemic. Many of those Black Americans may have been living in pharmacy deserts, where naloxone might not be as readily available. Longstanding racial differences in the response to substance use disorder also compounds this overdose issue. Since the “War on Drugs” started, there have been greater incarceration rates for drug charges amongst Black individuals, especially men. Buprenorphine treatment for OUD, already hard to access because of stigma and legal restrictions, is less likely to be prescribed to people of color, despite the treatment’s life-saving properties, leaving methadone as the only other option proven to reduce death.
During expert testimony to Congress, methadone has been described as unacceptable to “suburban middle-class people with opioid use disorder,” which is “codified language for white people.” Strict laws restrict methadone access to treatment centers outside of the mainstream health care environment. These opioid treatment programs are most commonly located in the urban core, where communities of color more commonly reside as a consequence of other historical structural racist policies (such as red-lining). Methadone is dispensed in limited quantities under direct supervision, sometimes for years, making it even more burdensome for patients to maintain a normal lifestyle and employment while treating their opioid use disorder. The question of whether such therapy is sustainable may prompt individuals to abandon it, cycling back to unregulated opioids and raising the risk of overdose once more. Even though pharmacies in other countries permit dispensing of methadone for OUD, legislation prohibits this in the US, even though research shows pharmacy availability would increase access.
THE OVER-THE-COUNTER SOLUTION
Naloxone is currently FDA-approved as a prescription, but it can be dispensed or distributed to individuals by prescription or standing orders in a variety of settings, including emergency departments, pharmacies, and community outreach agencies. Our proposal to maximize accessibility is to convert naloxone to over-the-counter status, just as it was done with Plan B. Naloxone meets all FDA criteria for becoming an over-the-counter 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. The FDA expressly supports this change and even developed a drug facts label for the medication. Instead of approving more expensive, unnecessary, or higher dose prescription naloxone formulations, efforts to increase naloxone possession should be prioritized.
Rhode Island has one of the highest opioid overdose rates in the nation, peaking in 2020 notwithstanding extensive naloxone distribution through a variety of channels including co-prescribing, community partners, pharmacies, and hospitals. Despite an annual recorded distribution of more than 20,000 naloxone kits since 2019, naloxone is just not saturating the needed areas in the most hard-hit communities. In fact, downtown Providence, Rhode Island, could be described as a pharmacy naloxone desert. In the center of the city, clusters or hotspots of opioid overdoses have frequently occurred, even with heroic efforts from community-based groups distributing naloxone there. When these hotspots are superimposed over a map of pharmacy locations, one will quickly see that only a single store is near this area.
Reclassifying naloxone as over the counter would be one way to address this need in areas without pharmacies and would also attend to racial disparities that coexist among medication deserts. In Las Vegas, Nevada, the use of vending machines to distribute clean needles amongst people who inject drugs has been occurring since 2017 with great success. Today, items such as naloxone, sharps containers, and hygiene kits are also available in the machines and can be accessed with a participant ID card. During 2019, 631 naloxone kits were dispensed at a rate of one kit per person every month as needed. Such an arrangement targets individuals who may be unable or unwilling to access the health care system, a demographic that is not easily reached. Because of this triumph, the Rhode Island Department of Health is exploring the deployment of harm-reduction vending machines as well.
CONCERNS FOR OVER-THE-COUNTER SWITCH
Before Plan B was changed to nonprescription status, opponents of the move claimed that increased availability of emergency contraceptives would cause women to engage in risky behaviors such as unprotected sex more often, potentially driving up abortion rates. However, this has not been true in cases where emergency contraceptive access increased. For instance, after Germany approved levonorgestrel and ulipristal emergency contraceptives for over-the-counter use, access increased; in areas with highest use, fewer abortions were actually performed. The moral hazard framework fails when applied to increased naloxone access as well.
Another concern is that moving naloxone over the counter would mean those who previously relied on insurance to cover the cost might now have to pay out of pocket. Yet, not all manufacturers will sell their products as nonprescription—consider how fluticasone propionate nasal spray (Flonase) can be paid for by some insurance plans as long as the over-the-counter packaging is not dispensed. Under the Affordable Care Act, most third-party payers, including Medicaid, provide coverage of Plan B and other emergency contraceptives when prescribed, even though levonorgestrel preparations are now over the counter. Similarly, certain states such as Rhode Island mandate insurance coverage of naloxone, which can easily be continued if the medication becomes nonprescription.
Finally, while over-the-counter status would allow naloxone to be sold in locations such as convenience stores or grocery markets without any communication with pharmacists or health care providers, it would not preclude conversations at other points of access such as emergency departments, pharmacies, and provider offices. The sacred physician-patient relationship would not be altered by over-the-counter naloxone. In fact, if naloxone and discussions on OUD become more commonplace in society, it may even provide the impetus for doctors to talk to their patients about substance use, focusing on those with identified risk factors for opioid overdose. The main goal of the nonprescription switch would be to shrink the size of medication deserts, not discourage interactions with the health care system. Consider how the ACOG advocates for universal, over-the-counter access to emergency contraceptives and birth control while encouraging women to seek and sustain medical care for their overall reproductive health.
PUBLIC HEALTH COST SHARING AS THE ULTIMATE SOLUTION
Part of the difficulty in achieving universal, low-barrier, over-the-counter access to naloxone lies in the price to consumers. Over-the-counter naloxone nasal spray will likely be costly, even if multiple generics become available to create market competition. While the federal government could contract with manufacturers under 28 USC section 1498 to produce inexpensive products in bulk, this does not entirely eliminate all payments and cost sharing, especially for people with limited financial means.
Because of the more than $1 trillion in costs associated with opioid overdose and opioid use disorder, we propose to sustainably supply over-the-counter naloxone through public funding streams. This could be achieved at no cost to taxpayers through innovative legislation such as state opioid taxes, which have already been enacted in Delaware, Minnesota, New York, and Rhode Island. However, concerns about discouraging drug wholesalers from servicing the state due to these levies are valid. In New York, independent pharmacies often limit their opioid supply in an attempt to minimize losses to taxes. Costs may also be passed onto patients who are prescribed opioids if pharmacies are charged more for these medications. One temporary fix may be obtained from opioid manufacturer settlements. Purdue Pharma and the Sackler family have offered billions of dollars to states that could fund several years of affordable, accessible naloxone. Most recently, without even admitting wrongdoing or liability, Johnson & Johnson will be paying New York State more than $230 million dollars to settle its role in the opioid epidemic. At the same time, extended expiration dating and economies of large-scale purchases increase and extend potential inventories of naloxone as well. Over time, positive outcomes of fewer overdoses may translate into decreased costs in emergency departments, aided by cost-effective efforts to connect patients with nonfatal overdoses to treatment. Not only is naloxone a good return on investment for hospital costs, the priceless benefit of saving lives is also included.
Despite current efforts to make naloxone readily available through health care channels and community organizations, as in the case of Rhode Island, opioid overdoses have continued to increase. Although this rise is at least somewhat caused by the consequences of the COVID-19 pandemic, we still need to enact bold changes to increase access to naloxone for the most vulnerable people. An over-the-counter switch of naloxone, combined with sustainable public funding, is a starting point that hopefully can begin to turn the tide against the opioid crisis.
(originally published in Health Affairs on July 2, 2021 – by Kendra Walsh and Jeffrey Bratberg)