CDC to Clinicians: Look Out for Medetomidine in Opioid Overdose

 Clinicians should be on alert for signs of medetomidine exposure and withdrawal in suspected overdose cases, public health experts said Thursday during a CDC webinar.

Hosted by the agency's Division of Overdose Prevention, the webinar highlighted growing concerns about medetomidine's increasing presence in the U.S. illicit drug supply -- often mixed with fentanyl -- and the clinical challenges of treating patients exposed to it. Experts also outlined management strategies for treating withdrawal and emphasized the difficulty of predicting which patients will require hospitalization or admission to the intensive care unit (ICU).

"We've had a hard time predicting who's going to be escalated," said Samantha Huo, MD, MPH, assistant professor of emergency medicine at the University of Pennsylvania's Perelman School of Medicine in Philadelphia. The clearest predictor -- and "also the most obvious one," she said -- is a prior hospitalization for withdrawal.

Although U.S. drug overdose deaths dropped 25% in 2024 compared with the previous year, overdoses remain the leading cause of death for adults ages 18 to 34, said Allison Arwady, MD, MPH, director of the CDC's Injury Center.

Medetomidineopens in a new tab or window is a synthetic alpha-2 adrenoceptor agonist similar to dexmedetomidine and clonidine that causes deeper, more prolonged sedation and lower heart rate and blood pressure, rather than life-threatening effects. While the FDA has approved it as a sedative and analgesic for dogs, it has not done so for human use.

It works by binding "very tightly" to the alpha-2 receptor on the end terminal, said Jeanmarie Perrone, MD, director of medical toxicology and addiction medicine at the University of Pennsylvania's Perelman School of Medicine.

"That means there is decreased norepinephrine released, which is what results in the hypotension," Perrone said. "Medetomidine has increased selectivity for that alpha-2 receptor, and that actually acts to make it more potent."

Experts say medetomidine's sudden appearance in street drugs may mirror the rise of xylazine, or "tranq," a long-acting, non-opioid sedative added to opioids like fentanyl. The combination of heavy sedation from medetomidine and respiratory depression from fentanyl could lead to sudden overdose in some people, experts previously told MedPage Todayopens in a new tab or window.

Speakers cited a prior CDC reportopens in a new tab or window about a May 2024 cluster of medetomidine overdose cases in Chicago in which the patients had taken fentanyl but the overdose-reversing drug naloxone (Narcan) didn't appear to work. An investigation by the city's health department reported 12 confirmed cases of medetomidine-involved overdose -- the largest to date -- as well as more than 160 probable or suspected cases including a possible death.

In a separate analysis discussed by the Penn team, researchers evaluated 165 patients hospitalized with suspected medetomidine withdrawal treated at three Philadelphia hospitals between September 2024 and January 2025. Of those, 83% required treatment with dexmedetomidine, and 90% were admitted to the ICU.

"It certainly gives you a picture of how sick people can be," Huo said.

The Penn researchers also cited separate data from Philadelphia's health departmentopens in a new tab or window showing a spike in emergency department visits for withdrawal as the prevalence of medetomidine in local fentanyl samples in the city rose.

Withdrawal symptoms tend to follow a recognizable progression, Huo said. They start with nausea and vomiting, then progress to tachycardia, severe hypertension, tremors, and delirium. In severe cases, intubation is required.

"Nausea and vomiting is very much a common feature of opioid withdrawal, so at first it can be hard to tell if the patient is experiencing opioid withdrawal or medetomidine withdrawal," Huo said.

That uncertainty is a key challenge in treatment because clinicians don't often know what specific substances a patient has used.

"With the patient in front of you, they may not know what's in their drug supply, so you're left guessing," Huo said.

For instance, while xylazine withdrawal typically presents with restlessness and anxiety, "we really have not seen it result in vital sign changes," she added.

"I think opioid withdrawal is challenging because there are so many overlapping features. I think if you treat your patient aggressively in the case of opioid withdrawal ... that should have an effect," Huo said. "And if you're really not seeing an effect from that, then I would suggest thinking about medetomidine withdrawal."

https://www.medpagetoday.com/publichealthpolicy/publichealth/116893