The Shifting Landscape of a Fentanyl Adulterant: Moving From Xylazine to Medetomidine.

Medetomidine has been increasingly found in the illegal opioid supply across the country over the last few years. In 2024, it replaced xylazine as the most common adulterant of the illegal opioid supply in the Philadelphia area. Medetomidine is estimated to be over 100 times as potent and selective for the alpha-2 receptor than xylazine. This leads to increased sedative effects compared with other alpha-2 agonists and in some patients, a severe autonomic withdrawal syndrome when medetomidine is abruptly stopped. Severe hypertension, tachycardia, vomiting, and tremors have been seen, often requiring hospital admission and critical care. As a result, the capacity of local health systems and ability to accurately triage patients to the proper level of care have been stretched. Drug checking and testing of biospecimens for medetomidine remains limited. Clinician and public health awareness of this new entity will be foundational to robust responses to this next adulterant threat.