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Xylazine, a tranquilizer for animals including horses and cattle, has increasingly been found in the illegal drug supply chain in Canada. The drug is most often found mixed with fentanyl, and often, users don't know they're ingesting it.

Identifying the drug in patients is difficult because it doesn't show up on a typical urine screen. In Canada, it has been increasingly identified in illicit drug samples since 2019. The problem is also increasing in the United States, which last year declared the xylazine-fentanyl combination an emerging threat.

Signs of Xylazine

To help clinicians with an overview of xylazine and treatment options, Peter Wu, MD, MSc, and Emily Austin, MD, both at the Division of Clinical Pharmacology and Toxicology at University of Toronto, Toronto, Ontario, Canada, developed a five-point summary that was published online on February 5, 2024, in the Canadian Medical Association Journal. Wu is also part of the university's department of medicine.

"Xylazine should be considered when presentations are discordant with what would be expected from opioids only," the authors wrote. The drug has no approved use in humans.

Case reports that suggest xylazine, also called "tranq or tranq dope" may cause sedation, bradycardia, low blood pressure, and, sometimes, high blood pressure, Wu and Austin wrote.

Wounds Offer Clues

Xylazine has also been linked with severe ulcerative wounds that are different from those seen with typical intravenous drug use. "Lesions may arise from any route of exposure, and wounds can occur both at or remote from injection sites," the summary stated. Wound care and antibiotics will be necessary in the case of secondary infection. Some reports have shown that the wounds can lead to amputation.

Suspected Opioid Overdose

The priority when managing suspected overdose from opioids possibly mixed with xylazine is to treat opioid-induced respiratory depression with naloxone and use supportive airway measures.

But caution is warranted. "Naloxone reverses opioid toxicity but has no effect on the sedating properties of xylazine, which may persist," wrote the authors.

Xylazine case reports have increased in the past year in Canada, said Wu.

He told Medscape Medical News that the paper isn't meant to sound an alarm and that he doesn't want clinicians overly distracted from the work of addressing the primary concern, which is opioid use and connecting patients with resources, particularly addiction specialists. But because information has been scant and varied, he said, he wanted clinicians to know the core realities.

Testing a patient for xylazine is problematic, said Wu, because a clinician would have to first have the suspicion, then ask a local laboratory to test for xylazine. If that request is denied, then the physician would have to outsource the testing, and, Wu said, "the turnaround time is usually quite long."

Managing Withdrawal

Discomfort, irritability, and autonomic instability may occur during a patient's withdrawal from xylazine, the authors wrote. Opioid agonist therapy will treat only the opioid part of the withdrawal. Other agents such as clonidine, benzodiazepines, or gabapentin may be needed to address the xylazine withdrawal.

Wu said that it's unclear why xylazine was introduced into the illegal drug supply, but he noted that cutting an opioid with another substance typically increases the bulk and the financial gain for dealers. Whether adding xylazine makes the combination more deadly is also unclear, he said.

Hayley Thompson, project manager for Toronto's Drug Checking Service, said that about 10% of the fentanyl samples they check are laced with xylazine. She added that it's important to note that xylazine is just one of the contaminants mixed into the illicit drug supply.

"We see benzodiazepine-related drugs in about 50%-60% of expected fentanyl samples," she said. All these drugs in combination with fentanyl put people at a higher risk for overdose.

The larger issue, she said, is that "people have to access these drugs currently from an unregulated supply. There is no safeguard. What they're being exposed to is an incredibly volatile and contaminated supply."

The Drug Checking Service has five collection sites where people can drop off a sample of their drug — an amount "about the size of a typical matchhead," said Thompson — to see the composition and then make consumption choices. Patients who are reluctant to offer a sample can have a cooker or filter tested instead.

"We say that drug checking is a Band-Aid solution," she said. Nevertheless, it is an "absolutely necessary public health service in the absence of a readily available, regulated drug supply."

Austin received honoraria for speaking at emergency medicine conferences as an invited presenter about toxicology cases in the emergency department. No other financial relationships were declared. Thompson declared no relevant financial relationships outside of her employment with the Drug Checking Service.

Marcia Frellick, a graduate of Northwestern University's Medill School of Journalism, has been a Chicago-based healthcare journalist for more than 15 years. Her move to writing followed a progression of editing roles at the St. Cloud Times, the Iowa City Press-Citizen, the Cincinnati Enquirer, and the Chicago Sun-Times. Her writing has appeared in the Chicago Tribune, Science News, and Northwestern Magazine in addition to Medscape Medical News, MDEdge, and WebMD.