Tox In Focus

Focused Clinical Reference

Vol. 04 · Xylazine · May 2026

Drug Quick Reference

Drug Class / Mechanism

alpha-2 Adrenergic agonist

Non-opioid sedative / analgesic

Street Names

“Tranq” · “Tranq dope”

Often unlabeled in illicit supply

Routes of Administration

Intravenous injection (primary)

Nasal insufflation / oral ingestion

Commonly Detected With

Fentanyl · Heroin

Cocaine · Methamphetamine

Metabolism

Hepatic; see UDT Considerations

Glucuronide conjugation

Window of Detection

Not established (illicit exposure)

Half-life ~23–50 min; est. <24 h

Control Status

Not CSA scheduled

XYLAZINE

A veterinary sedative adulterating the illicit opioid supply

Xylazine is a non-opioid veterinary sedative now a primary adulterant in the illicit fentanyl supply. Naloxone does not reverse xylazine. Wound necrosis at injection sites is a hallmark clinical finding.

Why This Matters Now

DEA NFLIS data show xylazine detections rose from 149 in 2015 to 23,998 in 2024 (>160-fold increase). DEA declared it an emerging drug threat in 2023.

⚠ Wound complications are increasing ER utilization and creating new care demands for treatment programs. Prepare now regardless of current local detection rates.

Clinical Presentation

INTOXICATION

Deep sedation

Bradycardia

Hypotension

Respiratory depression

Miosis

Skin/wound necrosis

Hyperglycemia

Hypothermia

WITHDRAWAL

Onset: 8–12 hrs after last use

Anxiety / agitation

Diaphoresis

Tremor

Hypertension

Tachycardia

Refractory to opioid protocols

Important: Naloxone will not reverse xylazine effects. Administer it anyway; xylazine is almost always co-detected with fentanyl and naloxone addresses the opioid component. No xylazine reversal agent is currently approved for human use.

UDT Considerations

Standard urine drug test panels, including expanded panels, will NOT detect xylazine. Detection requires a laboratory test specifically validated for xylazine, typically by LC-MS/MS. Confirm with your laboratory whether xylazine is included before assuming a result reflects exposure status.

Clinical Guidance

Maintain high suspicion in any fentanyl-exposed patient with skin wounds, ulcers, or necrosis at or away from injection sites; refer to wound care or infectious disease early.
Administer naloxone for any suspected opioid overdose even when xylazine co-exposure is suspected; continue rescue breaths since naloxone will not reverse xylazine-related sedation or respiratory depression.
Withdrawal may require benzodiazepines and is often refractory to standard opioid-only protocols; plan for extended monitoring.

Point-of-Care Testing Availability

Available strips

Xylazine-specific lateral flow immunoassay strips are commercially available (e.g., SAFe-X, Premier Biotech; Rapid Response, BTNX). Result in approximately 1 minute. One line = positive; two lines = negative.

Clinical use

Appropriate for screening in harm reduction, ED triage, and treatment program intake settings when LC-MS/MS is not immediately available.

Limitations

Not FDA cleared for clinical diagnostic use. A negative strip result does not exclude xylazine exposure; confirmatory LC-MS/MS is required for clinical documentation.

XYLAZINE | Clinical & Program Guidance

Tox In Focus Vol. 04 · May 2026 · Page 2 of 2

Interpreting the Test Result

▲ If Testing Is Positive

Confirms exposure, not severity. Does not indicate dose, timing, or other substances present.

Does not change naloxone use. Give naloxone for any suspected opioid overdose; it addresses the fentanyl component.

Screen for wounds. Check for injection-site wounds at every visit, even if none are visible yet.

▼ If Testing Is Negative or Not Done

A clean standard panel proves nothing. Routine UDT panels do not include xylazine; a negative result does not rule out exposure.

Don’t lower your guard. Treat wounds, sedation, or clinical signs as possible xylazine exposure regardless of panel results.

Confirm what was tested. Ask your laboratory whether xylazine was included before treating any result as informative.

Metabolism & Urinary Markers

The liver metabolizes xylazine into several compounds. Laboratories may report the parent drug, one or more metabolites, or both. Ask your laboratory which markers their xylazine test includes.

Metabolite	Clinical Significance
Xylazine (parent)	The unchanged drug; the primary target for most xylazine-specific LC-MS/MS tests.
Sulfone-xylazine	The most abundant urinary metabolite, often at higher concentrations than the parent drug. Frequently co-reported.
4-Hydroxy-xylazine	Selective for xylazine and not shared with lidocaine; unlike the metabolite 2,6-dimethylaniline (also produced by lidocaine), it confirms xylazine rather than lidocaine exposure.
OH-oxo-xylazine	Common secondary metabolite; typically detected alongside xylazine and sulfone-xylazine.
Oxo-xylazine	Minor metabolite; present in only a small fraction of specimens.

Clinical & Program Guidance

Wound Care & Withdrawal Management

Screen for wounds at every visit. Look for skin breakdown, ulceration, or necrosis at and away from injection sites; untreated necrotic wounds can progress to amputation, so refer to wound care or infectious disease early.
Expect withdrawal beyond opioid timelines. Onset typically 8–12 hours after last use; can be more severe and prolonged than opioid withdrawal alone.
Plan for benzodiazepines. Withdrawal is often refractory to opioid-only protocols; anticipate need for benzodiazepines and extended monitoring.

Supervision & Harm Reduction

Naloxone still comes first. It will not reverse xylazine sedation, but give it anyway; xylazine is almost always co-detected with fentanyl.
Reinforce “never use alone.” Xylazine sedation can outlast opioid effects, leaving a person unresponsive after naloxone would normally have worked.
Pair test strips. Fentanyl test strips do not detect xylazine; xylazine-specific lateral flow strips are a separate product.
Make wound reporting safe. Participants should report skin changes without fear of sanctions so problems are caught early.

Key References

DEA Drug Threat Assessment 2023. U.S. Drug Enforcement Administration.
Kariisa M, et al. Illicit fentanyl-involved deaths with xylazine detected. MMWR 2023;72:721–727.
Friedman J & Shover CL. Charting the fourth wave: supply-side and demand-side factors. Drug Alcohol Depend 2022;233:109380.
CDC Overdose Prevention: Xylazine 2024. Centers for Disease Control and Prevention.
Datta P, Waters K, White CM. Naloxone instructions insufficient in era of xylazine/medetomidine adulteration. J Pharm Technol 2025;41(3):151–154.
Lin Z & Crews B. Xylazine and major urinary metabolites detected in patients positive for fentanyl and xylazine. J Anal Toxicol 2026.
US Food and Drug Administration. FDA Alerts Health Care Professionals of Risks to Patients Exposed to Xylazine in Illicit Drugs. November 2022.
Meyer GM, Maurer HH. Qualitative metabolism assessment and toxicological detection of xylazine in rat and human urine using GC-MS, LC-MSn, and LC-HR-MSn. Anal Bioanal Chem 2013;405(30):9779–9789.

DISCLAIMER: This document is intended for clinical reference and educational purposes only. It does not constitute medical, legal, or professional advice and should not replace independent clinical or programmatic judgment. Content reflects published data available at time of preparation. ToxiPharm LLC makes no warranties regarding completeness or applicability in all settings. | © 2026 ToxiPharm LLC | toxipharm.org