Fentanyl is increasingly being mixed with xylazine, the Drug Enforcement Administration warned Monday in its first such alert about an emerging drug threat since 2021.

The DEA has seized mixtures of fentanyl and xylazine in 48 of 50 U.S. states, DEA Administrator Anne Milgram said. Nearly a quarter of fentanyl powder tested by DEA labs in 2022 had xylazine, also known as tranq, mixed into it.  

“Xylazine is making the deadliest drug threat our country has ever faced, fentanyl, even deadlier,” Milgram said. 

The number of overdose deaths nationwide surpassed 107,000 between August 2021 and August 2022, the Centers for Disease Control and Prevention found. Two-thirds of those deaths involved fentanyl, but data has not been shared on how many of those deaths also involved xylazine.

Xylazine is approved for animals as a sedative, but it can cause severe, necrotic skin ulcerations in humans, the DEA said. The rotting of human skin may lead to amputation. Fatal overdoses are more difficult to prevent when xylazine is mixed with fentanyl. Naloxone, also known under the brand name Narcan, does not reverse the effects of xylazine. 

The Food and Drug Administration had earlier warned health care professionals about xylazine’s presence in the illegal drug supply. The FDA alert noted that while xylazine is most often found in combination with fentanyl or heroin, it’s also sometimes mixed with methamphetamine and cocaine.

Public health officials in cities on both sides of the country – from San Francisco to Philadelphia – have warned of overdose deaths linked to xylazine. The veterinary sedative can be found in 90% of Philadelphia’s dope supply, CBS News Philadelphia reported.