Naloxone use has increased in recent years in response to the nation’s opioid crisis. Once only available to health care professionals, it is now obtainable by prescription for persons at risk for substance overdose and their families. Increasing its availability is seen by some as an “over-the-counter solution” to the opioid problem. However, while naloxone has been viewed as relatively safe, with a low side effect profile when appropriately dosed and monitored, it is not without safety concerns that may go unrecognized or misattributed to other causes.

Here we present a case study of a 41-year-old female who presented to our medication-assisted treatment (MAT) clinic complaining of sudden onset weight gain, shortness of breath, upper and lower extremity peripheral edema, tachycardia, insomnia, and nocturnal enuresis. These symptoms made it difficult for her to work at her housekeeping job, resulting in missed workdays. She had seen a primary care provider for her symptoms and been prescribed a rescue inhaler for her shortness of breath. This patient had previously been treated for opioid use disorder with buprenorphine/naloxone and experienced similar symptoms, which disappeared when she relapsed on opioids. However, symptoms reappeared upon resuming her prescribed treatment.

The patient was identified as experiencing side effects to naloxone, causing noncardiogenic edema. Her MAT medication was switched to buprenorphine. Within two weeks her heart rate had returned to normal, she had lost weight, and she no longer had nocturnal enuresis or needed the rescue inhaler. Her peripheral edema resolved so she was able to walk better and resume work. At the same time, buprenorphine continued to relieve her cravings.

There is a dearth of information related to naloxone-induced edema. Our patient had not received a formal evaluation of pulmonary edema, but her pulmonary and cardiac symptoms were consistent with that diagnosis. Although pulmonary edema is mentioned in the product literature, peripheral edema is not. A literature search indicates that the number of case studies on naloxone-induced pulmonary edema have increased since 2018, but only one other case of naloxone-induced peripheral edema was discovered.

Naloxone is used in a variety of settings by differing types of health care providers. As the number of persons treated with naloxone increases, there will likely be a corresponding increase in incidences of pulmonary and/or peripheral edema as side effects. Providers and patients who are not aware of these manifestations and their relationship to naloxone treatment may easily attribute presenting symptoms to cardiogenic or other causes, as this case illustrates. It is important for providers in all settings to consider new onset shortness of breath and edema within the context of the person’s whole health and to be aware of their implications for mental as well as physical health.

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