From Risk to Rescue: What Pharmacists Should Review Before Recommending Naloxone

The opioid crisis reached a historic peak in 2022 with 107,941 overdose deaths, and although numbers declined slightly in 2023, they remain alarmingly high.¹ In July 2025, the FDA announced that major safety labelling changes would apply to all opioid pain medications to emphasize the risks of long-term use, such as addiction, misuse, and overdose.² The regulatory update highlights the importance of opioid-related harm management and emphasizes the need for early interventions at the site of care. Naloxone (Narcan; Emergent BioSolutions), an opioid antagonist, remains a crucial tool in reversing potentially fatal opioid overdoses. An important skill pharmacists should possess is making sure that patients prescribed opioid pain medications, particularly medications being sent out from the hospital, are safeguarded adequately from overdose risk. Given the current situation, it is even more vital for pharmacists to be aware of the appropriate time and procedure for utilizing naloxone, as they are positioned to reduce the risks related to opioid prescribing.

Opioid Overdose and Naloxone: A Vital Intervention

Opioid-related deaths accounted for 80% of drug overdose deaths in the US in 2021, underscoring the need for preventive measures in high-risk populations.³ Naloxone works by displacing opioids from their receptors and quickly reversing the life-threatening respiratory depression caused by an overdose.⁴

In many cases, prescribing or offering naloxone can significantly reduce the risk of fatal overdose​.⁵ Pharmacists should recommend naloxone when patients are prescribed opioids exceeding a daily morphine milligram equivalent (MME) of 50 to 90.⁵ Several states have mandated naloxone prescriptions when opioid doses meet or exceed these thresholds​.³ For example, Arkansas requires a coprescription of naloxone when the opioid dosage is equal to or greater than 50 MME per day. California recommends naloxone for patients receiving 90 MME or more. There is also a severe enhanced risk of respiratory depression or even death from overdose for patients taking both opioid and benzodiazepine medication. These drugs also need to be prescribed with restraints as they belong to the category of central nervous system (CNS) depressants usually used in treating insomnia or agitation and counteract the effect of opioids on breathing. Therefore, it is highly appropriate to prescribe naloxone to all opioid patients who are being treated with an additional benzodiazepine drug as well. Arkansas, Rhode Island, and South Carolina require prescription of naloxone simultaneously with this class of narcotic and benzodiazepines.³

MME Threshold Considerations

The MME is a standardized measure when seeking to assess the likelihood of an overdose among patients receiving opioid treatments.^3,5 MMEs organize databases to make it easier to compare different opioids or measure their impact when used with other drugs. Normally, the higher the number of MMEs, the more the chances of an overdose, more so among those patients who have no previous exposure to opioids or have a history of substance use disorder (SUD).

Different states implement different MME cutoffs for the prescriber to issue a naloxone coprescribing prescription. For instance, South Carolina and Arkansas state the threshold at 50 MME, whereas California and New Jersey will require naloxone when the doses of opioid analgesics reach or exceed 90 MME. In-hospice pharmacists have to remember that it is not enough to track only the MME of prescribed opioids but also the presence of other risk factors, such as benzodiazepine use or SUD history.

Adjusting for Benzodiazepine Use

When benzodiazepines are coprescribed with opioids, patients face an increased risk of overdose even at low opioid doses, so naloxone should be considered regardless of MME.^3,5 In Rhode Island and many other states, clinicians have adopted the rule to prescribe naloxone when even a single dose of any opioid is prescribed with a benzodiazepine. In Ohio, it is recommended that physicians provide naloxone if "benzo" and "opioid" are prescribed together, even though it is very unlikely that an 80-MME dosage would be given without such a recommendation.

Patients at Increased Risk of Overdose

Apart from MME thresholds, benzodiazepine consumption, and the history of SUD or prior overdose, pharmacists should be aware of other risk factors that lead to increased vulnerability to opioid overdose. These factors go far beyond the mere opioid dose and consist of drug-related and nondrug medical aspects.

The abuse or intake of alcohol is a major contributor to overdose risk.⁴ Alcohol is a CNS depressant that scales up the respiratory depression effects of opioids, especially when it is combined with benzodiazepines too. Other sedative-hypnotics and muscle relaxants also intensify the CNS depression.⁴ Pharmacists will need to review and ask patients about these potential drug interactions when feasible. It is also important to know that patients who previously initiated a high dose of opioids may have lost their tolerance if they have abstained for a longer period.⁶ This places them at substantial risk for overdose.

Nondrug Medical Risk Factors

Older patients are at an increased risk because they have increased pharmacodynamic sensitivity and decreased clearance that narrows the therapeutic window for opioids.⁷ Patients who experience sleep apnea or other sleep-disordered breathing conditions are at a high risk for developing opioid-induced hypoventilation and respiratory arrest.⁵ The presence of liver disease means there is less metabolism for the opioid to be broken down properly, which leads to the drug's increased action of causing sedation and toxicity.⁸ Moreover, kidney disease that does not excrete an active metabolite, such as morphine-6-glucuronide and normeperidine, which are about half as potent as meperidine, has twice the risk of CNS stimulation effects, including sedation, respiratory depression, and seizures.⁷

Practical Considerations for Pharmacists

Pharmacists should work with providers to review for potential naloxone prescription to patients after evaluating MME levels, concurrent benzodiazepine use, relevant patient history, and drug interactions. If a naloxone prescription is appropriate, pharmacists must take several steps to ensure appropriate use.

There is a need for pharmacists to offer proper training to the patients on how naloxone should be used. There are several different dosage forms of naloxone, and patient preference may play a role in which dosage form is most appropriate.^4,5 Moreover, patients and their caretakers must be trained in identifying overdose effects and giving naloxone without delay.

Pharmacists must remain aware of the regulation of naloxone prescription authority that varies from one state to another, as these may differ in their MME thresholds and risk factor considerations.³ For example, a prescriber in Vermont is required to prescribe naloxone alongside any opioid dose exceeding 90 MME. In New Jersey, it is required that patients taking opioids and benzodiazepines be also prescribed naloxone.

It is also important to emphasize to the patient or caregiver that the possession of naloxone should not be interpreted as abuse of opioids. Instead, it is a measure that aims to forestall the possible dangers that may arise from an opioid treatment. Reducing stigma toward naloxone may provide more acceptance of this important intervention by patients. Lastly, naloxone also remains underutilized in practice. In a retrospective cohort of surgical patients prescribed opioids, only 1.7% were coprescribed naloxone, underscoring an important gap in care where pharmacists can intervene.⁸

Naloxone Distribution at UMMC Emergency Department Through Project AUTO-MED

The Mississippi State Department of Health (MSDH), in collaboration with the University of Mississippi Medical Center (UMMC), has implemented a grant-funded naloxone distribution initiative in the emergency department through Project AUTO-MED. According to Ashton Smith, PharmD, pharmacist with the MSDH Clinical Pharmacy Division, the program supplies take-home naloxone kits at emergency department (ED) discharge and is exploring opportunities to coordinate with other hospitals. Sophie Durham, deputy director of the MSDH Opioid and Substance Use Program, added that naloxone distribution has already extended to UMMC Jackson, UMMC Grenada, and Baptist Oxford. The program also provides fentanyl test strips, with hospitals able to request supplies through a centralized form. To initiate distribution, hospitals must upload a letter of support from their administration, and MSDH typically recommends starting with 20 to 25 boxes of naloxone, depending on hospital size. For example, UMMC Jackson began with 60 boxes and has since replenished with 25 more. Betsy G. Cox, PharmD, BCCCP, an ED pharmacist, explained that the primary objective of the initiative is to advance uniform and timely management of opioid use disorder using medications in the ED. Physicians assess patients using the Clinical Opiate Withdrawal Scale to guide suboxone dosing, and any patient who qualifies for suboxone is also considered appropriate to receive naloxone at discharge. A DATA waiver (X-waiver), long considered a barrier preventing health care providers from prescribing suboxone, is no longer required.⁹

Although pharmacists do not play a formal role in real-time discharge decisions, they provide education when available and assist with logistical support, such as maintaining the secure storage of naloxone kits, which are tracked through inventory logs when distributed alongside fentanyl test strips. Cox noted that the program has been well received by ED staff and patients, although outcomes data have not yet been evaluated because the program is less than a year old. Although no major challenges or barriers have been reported, the pharmacist and other staff agree that expanding naloxone access beyond the ED would likely require additional leadership from physicians, with nursing and pharmacy ready to support such efforts.

Nonopioid Pain Medication Alternatives

Newer nonopioid pain medications are being developed that are designed to control pain while limiting the adverse events and risks of opioid medications, like respiratory depression. Suzetrigine (Journavx; Vertex Pharmaceuticals) was FDA-approved in January 2025. Its novel mechanism of action, which targets voltage-gated sodium channels in neuron conduction of pain, is being studied by multiple drug companies as another avenue to control pain.¹⁰

Conclusion

Naloxone is one of the measures used in the prevention of death from opioid overdose. It is the work of the hospital pharmacist to identify risk factors and recommend naloxone to the prescriber. Regarding MME limits, by investigating concomitant benzodiazepines and gathering patient information, pharmacists can ensure that the necessary risk group of patients are given the correct recognition. The opioid epidemic is ongoing. Naloxone continues to be a significant support to help those who are at risk of overdose, and pharmacists are one of the major promoters of such medications.

REFERENCES

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7. Gelot S, Nakhla E. Opioid dosing in renal and hepatic impairment. August 20, 2014. Accessed September 22, 2025. https://www.uspharmacist.com/article/opioid-dosing-in-renal-and-hepatic-impairment

8. Huang LC, Nibley H, Cheng M, et al. Naloxone co-prescriptions for surgery patients prescribed opioids: a retrospective cohort study. Surg Pract Sci. 2023;15:100217. doi:10.1016/j.sipas.2023.100217

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