17 Nov 2025
Overview
Alpha-2 agonists—particularly xylazine and medetomidine—are increasingly detected in the illicit drug supply, and almost always are associated with the presence of fentanyl. These compounds are potent non-opioid sedatives and pose significant clinical risks, including profound sedation, bradycardia and hypotension. Importantly, their effects are not reversed by naloxone, complicating overdose management.
Key Clinical Concerns
- Xylazine has been a known adulterant in fentanyl for several years
- Medetomidine is now emerging as a replacement for xylazine, based on recent internal data
- These agents are not approved for human use and are typically used in veterinary medicine
- Their presence in illicit formulations may increase overdose severity and reduce responsiveness to standard opioid reversal protocols
New Testing Capability
To support clinical decision-making and surveillance, our new Alpha-2 Agonists Screen With Confirmation, Urine [703340] is available now. This panel includes:
- Xylazine and metabolite (4-hydroxy-xylazine)
- Medetomidine and metabolite (3-hydroxy-medetomidine)
- Detomidine
- Tizanidine
- Lofexidine
- BTMPS
Clinical Guidance
- Fentanyl detection remains a strong proxy for potential alpha-2 agonist exposure
- In the absence of alpha-2 agonist testing, assume probable exposure when illicit fentanyl is present
- A negative alpha-2 agonist result does not rule out exposure, due to variability in drug metabolism and detection windows
- Naloxone should still be administered to reverse opioid effects, even though it does not counteract alpha-2 agonist toxicity
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