Growing Tranq Threat Poses Challenges for PCPs

The widening threat of the animal tranquilizer xylazine, otherwise known as tranq, which has been found in illegally manufactured fentanyl, necessitates wider testing, a better understanding of its effects, and more research on treatment options, according to a narrative review published Monday in the Annals of Internal Medicine.

“A lot of doctors and providers are asking about this drug,” said Joseph D’Orazio, MD, an addiction medicine specialist and medical toxicologist at Cooper University Healthcare in Camden, New Jersey, who led the review.

Xylazine is believed to prolong or intensify the effects of opioids, making it a popular additive to illegally produced opioids, particularly fentanyl, according to the Drug Enforcement Administration. Users end up in a zombie-like state with slowed breathing, and they sometimes develop skin ulcers. Because xylazine is not an opioid, common antidotes such as naloxone are ineffective. The White House has called the fentanyl-xylazine combo an “emerging threat.”

“Xylazine is making the deadliest drug threat our country has ever faced, fentanyl, even deadlier,” said DEA administrator Anne Milgram, in a statement on the agency’s website. “DEA has seized xylazine and fentanyl mixtures in 48 of 50 States. The DEA Laboratory System is reporting that in 2022 approximately 23% of fentanyl powder and 7% of fentanyl pills seized by the DEA contained xylazine.”

D’Orazio paired clinical experience with available research to provide guidance on the care of patients exposed to xylazine.

He and his team issued a call for more research on the drug’s effects, including more details on dependency and withdrawal.

Testing a patient who may have been exposed to xylazine requires forensic lab capabilities, which makes testing complicated and costly. The review found no evidence of the origin of the drug or why it causes open sores.

The review calls for more education of providers, including primary care physicians, on the treatment and care of patients who have used xylazine and fentanyl. The authors also call for expanding standard urine analysis to test for xylazine and for intensifying surveillance of the drug supply and distribution of xylazine test strips.

The authors of an editorial that accompanied the journal article urged the healthcare community to get ahead of xylazine before the crisis worsens.

“Not testing for xylazine in current unaffected areas and populations may lead to delays in responding if and when the drug becomes prevalent in the drug supply,” the authors wrote.

Xylazine was detected in 90% of street opioid samples tested in Philadelphia in 2021, and a toxic surveillance study of drug paraphernalia in Maryland found xylazine in 80% of samples tested between 2021 and 2022.

D’Orazio stressed that although Narcan is ineffective in treating xylazine, because the sedative is almost always mixed with fentanyl or another opiate, the opioid antagonist should still be used in emergencies.

Angelique Campen, MD, an emergency medicine physician at Providence St. Joseph Medical Center in Burbank, California, said she has seen an increase in patients entering the emergency department under the influence of what seems like fentanyl or heroin, but standard treatments such as Narcan have a limited effect. These patients remain in a prolonged period of sedation.

Recently, she admitted to her hospital’s intensive care unit a patient suspected of a xylazine overdose who was not responding to treatment.

Campen said that patients are screened for fentanyl, but because no test is available for xylazine, she presumed xylazine was causing the complication.

“It makes perfect medical sense to me that that’s what was going on,” Campen, who has worked at St. Joseph’s for 25 years, said. “I’m hoping with physicians being more aware of it that we can have that part of our regular urine drug screen.”

Campen also said she hopes an antidote is soon developed.

“If we can just keep delivering that message, hopefully, more and more people, it will get through to them,” she said. “Every time you’re taking this, even though you may have taken it a week before and been fine, you never know: the next dose you take may be the lethal dose.”

A review author reports being awarded $1000 to cover travel cost for Best Overall Abstract at the American Society of Addiction Medicine 2023 Annual Meeting. Another author reports receiving payments for training conducted as part of a NJDMAHS training grant to educate on substance use disorders. D’Orazio reports a $500 honorarium for a one time lecture on xylazine at Yale; and a $500 honorarium for speaking one to three times per year on various topics regarding opioid use disorder at the Health Federation of Philadelphia. No other disclosures were reported.

Ann Intern Med. Published online on October 9, 2023.

Robert Fulton is a reporter living in Los Angeles.

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