The FDA approves the second OTC naloxone – a step toward opioid crisis mitigation

Dear Editor,

On 28th July 2023, the Food and Drug Administration (FDA) approved the second over-the-counter (OTC) naloxone nasal spray, RiVive, with 3 mg naloxone hydrochloride to increase consumer access to naloxone without a prescription. The first OTC naloxone spray, Narcan, a 4 mg naloxone hydrochloride, received the FDA’s nod in March this year, and the first generic non-prescription nasal spray was also approved in July this year¹.

Naloxone is an opioid-specific antagonist that displaces heroin, fentanyl, and other prescription opioids from the mu-opioid receptor within 2–3 min of administration and rapidly reverses the effects of overdose². It can quickly restore normal breathing within 2–3 min of administration in persons with slowed or no breathing due to drug overdose. With ‘Remove the Risk’ awareness program, the agency aims at awareness across community settings of the safe disposal of unused opioids with the rising incidents of opioid use in younger population³.

Opioids have analgesic properties, but their euphoric and addictive properties have increased the number of people in addiction and dysfunctional lives and ultimately caused death. In the 12 months ending October 2021, over 105 000 Americans died from a drug overdose, with two-thirds involving fentanyl⁴. Timely administration of naloxone can reverse the effects of overdose and prevent progression to cardiorespiratory arrest.

While increasing access to naloxone is critical, the use of OTC products such as RiVive nasal sprays may result in several withdrawal symptoms, including pain, nausea, nervousness, and tremors in opioid-dependent individuals. Thus, efforts to improve accessibility must be balanced with proper education about proper administration and potential withdrawal symptoms⁵.

The predictive model of the Stanford Lancet Commission on the North American Opioid Crises predicted that expanding naloxone availability by 30% would prevent approximately 144 000 deaths over 5 years and 301 900 deaths over 10 years. Naloxone availability had a linear effect on the prevention of overdose-related deaths⁶.

Opioid users are highly stigmatized globally and may be perceived as a barrier for them to receive treatment, as well as for bystanders to intervene and administer naloxone to reverse overdose effects. The inadequate government funding for the treatments and the negative attitudes among healthcare providers, pharmacists, and the general public toward people with opioid-use-disorder (OUD) all reflect multifaceted stigma⁷. Increasing public access to naloxone through OTC availability can normalize it as a basic health product. Broader OTC access could reduce barriers currently caused by pharmacists and the need to identify one’s risk status when obtaining OTC services. This could increase people’s willingness to use it as a mainstream product for health safety.

Reclassifying naloxone with OTC increases its availability and accessibility to first responders to overdose incidents. It can also improve health outcomes in Patients with Opioid Use Disorder (PWOUD). OTC availability will spike naloxone sales from 15 to 179%⁸. It will have spillover effects and will bring in more investors and manufacturers, which will increase competition and reduce the costs of the naloxone product, making it more accessible to the general public.

Lay administration of naloxone nasal sprays is both effective and safe. Opioid Education and Naloxone Distribution (OEND) programs for laymen⁹, spreading awareness and knowledge of the recognition and management of overdose incidents, would increase the odds of recovery and ultimately reduce related mortality.

As per the manufacturing company, RiVive will be made available in 2024 ‘for costs lower than any other opioid antagonist nasal sprays’ and the manufacturer will make 200 000 doses for free¹⁰. The OTC status may also reduce the insurance coverage of naloxone, thus shifting the burden of purchasing, and a potential cost barrier may lower sales.

While naloxone nasal sprays aim to reduce drug overdose-related deaths, their impact on opioid misuse remains a concern. A multifaceted approach is required to mitigate the opioid epidemic involving naloxone accessibility, pharmacotherapy, psychosocial treatment, and so on⁶.

In conclusion, the FDA’s approval of RiVive, the second OTC naloxone, aims to reduce opioid overdose deaths by increasing access to this life-saving emergency medication. OTC status can help reduce stigma and improve accessibility. A low-priced OTC availability and awareness program is key to realizing its full benefits. Overall, expanded OTC access is a positive step; however, its impact on mitigating the underlying opioid epidemic requires further evaluation, and a multifaceted approach is required to tackle the increasing opioid misuse.

Ethical approval

Not applicable.

Consent

Not applicable.

Sources of funding

No source of funding.

Author contribution

S.N.Q.: conceptualization of the ideas; S.N.Q. and R.S.A.: writing of initial draft; D.S. and I.U.: reviewing and editing; S.N.Q.: supervision. All authors approved the final draft.

Conflicts of interest disclosure

The authors declare that they have no conflicts of interest.

Research registration unique identifying number (UIN)

Not applicable.

Guarantor

Sardar Noman Qayyum takes full responsibility for the work.

Provenance and peer review

Not applicable.

Data availability statement

No dataset was generated during the study.