Xylazine

Dr. Acharya
oud

Introduction 

Xylazine (aka “Tranq”) is alpha-2 adrenergic agonist that has been used as an adulterant of various substances including cocaine, heroin and fentanyl.

Epidemiology

  • DEA Laboratory resporting that in 2022, 23% of fentanyl powder and 7% of fentanyl pills seized contained xylazine.

  • Puerto Rico in 2000’s in PWID (People who inject drugs), then Northeast USA.

  • Called ‘tranq’ or ‘tranq dope’ when mixed with heroin or fentanyl.

  • Has been found sometimes with methamphetamines and cocaine, in addition to pills (percocet, xanax).

Mechanism

Papudesi et al 2023, Creative Commons


  • Alpha-2 agonist: decreasing sympathetic outflow (by decreasing norepinephrine and dopamine release)

  • Rapidly absorbed; IV 1-2min, IM/SQ/PO up to 15 mins

  • Highly lipophilic

  • Metabolism: rapid elimination, processed in liver (CYP450), excreted in urine (lasting 1-2 days)

  • Sedation, pain relief, and muscle relaxation in veterinary medicine

  • Consider other medical cause for sedation: syncope, hypoglycemia, hypothermia, seizure disorders, and cerebrovascular accidents.

  • Or other ingestions: opioid, benzo, barbiturates, etoh, other alpha 2 agonist overdose, beta blocker or calcium channel overdose

Intoxication/Overdose

  • Usually unintentional: patient’s not knowing the presence of adulterant

  • Some individuals seek it out as they say it increases and prolongs high, and delays withdrawal symptoms

  • Symptoms: CNS depression, bradycardia, hypotension, miosis, anticholinergic effects

  • Anecdotally, hear about the “naloxone resistant” overdose – consider coningestions (benzo, etoh) and metabolic disturbance (hypercarbia, hypoxia).

  • Overdose treatment:

    • Naloxone ineffective against xylazine, but still recommended to use as most overdoses are combination of xylazine and opioid.

    • Recent opinion seems to be that xylazine doesn’t have as much of a respiratory effect as opioids and its presence may actually be protective (because there is less opioid)

    • Several medications in veterinary medicine are available as alpha-adrenergic antagonists, but not approved for use in humans (atipamezole, tolazoline, yohimbine).

    • Some case reports from 1980’s that yohimbine or atropine may work

  • Treatment is largely supportive (ABC’s)

Withdrawal

  • Symptoms: Anxiety, Restlessness, Depressed mood, Body aches

  • Unclear if this is a real syndrome or confounded by medical conditions, opioid withdrawal, stimulant withdrawal. No criteria to diagnose xylazine w/d currently.

  • Withdrawal Treatment (based on case studies, see graphic below):

    • Alpha-agonists (to decrease noradrenergic activity) including clonidine 0.1-0.3mg q6-8hr (monitor for hypotension), tizanidine 2-8mg q8hr, dexmedetomidine IV infusion in ICU

    • Benzodiazepines

    • Gabapentin/Pregabalin

    • Phenobarbital

    • Olanzapine

  • MOUD treatment/withdrawal management: MOUD (suboxone/methadone) + adjunctive medication (Ondansetron, Acetaminophen, NSAIDS, etc.) 

Philadelphia Dept of Public Health Recs (available here: https://hip.phila.gov/document/3154/PDPH-HAN_Update_13_Xylazine_12.08.2022.pdf/) :

 Harm reduction:

  •  Xylazine test strips – false positive with levamisole, diphenhydramine, lidocaine, but very sensitive (2 micrograms/mL). 98% accurate with gas chromatography gold standard.

  • Could be less useful in a market where opioids are saturated with xylazine – no way to avoid.

  • Teach patients about hand hygiene, safe injection/inhalation practices, keeping wound clean/dry/covered.

Skin Wounds

  • Xylazine associated with progressive and extensive necrotic wounds, sometimes located far from site of injection, thought due to alpha-2 vasoactive effects

  • Start as small ulcers/blisters and progress to deeper, necrotic wounds. May display “swiss cheese” quality where there are pockets of viable tissue, differing from injection drug related wounds.

  • Slow and poor healing wounds, confounded by social factors, ongoing drug use

  • Exposure of tendon/bone -> chronic osteo

  • Consider biodegradable temporizing matrix for wound coverage

  • May require antibiotics, admission for intensive wound care, debridement. 

Testing

Difficult at this time, urine and blood tests exist, mainly at academic centers or research labs. Requires chromatography

References

  1. Department of Justice (DOJ), Office of Justice Programs (April 2023). The emerging threat of xylazine. Catching Up with COSSUP. Retrieved from: https://www.cossup.org/Content/Documents/Articles/RTI_Emerging_Threat_of_Xylazine_April_2023.pdf

  2. Doran, K.M., Fockele, C.E., & Maguire, M (2022). Overdose and homelessness_ Why we need to talk about housing. JAMA Network Open, 5(1):e2142685. doi:10.1001/jamanetworkopen.2021.42685

  3. Malayala, S. V., Papudesi, B., Bobb, R., et al. (2022) Xylazine-induced skin ulcers in a person who injects drugs in Philadelphia, Pennsylvania, USA. Cureus 14(8): e28160. doi:10.7759/cureus.28160

  4. McFadden, R., Wallace-Keeshen, S., Petrillo Straub, K., Hosey, R. A., Neuschatz, R., McNulty, K., & Thakrar, A. P. (2024). Xylazine-associated wounds: Clinical experience from a low-barrier wound care clinic in Philadelphia. Journal of Addiction Medicine, 18(1), 9–12.Retrieved from  https://doi.org/10.1097/ADM.0000000000001245

  5. Nunez, J., DeJoseph, M., & Gill, J., Xylazine (2012), A veterinary tranquilizer, detected in 42 accidental fentanyl intoxication deaths. The American Journal of Forensic Medicine and Pathology 42(1):p 9-11, doi:  10.1097/PAF.0000000000000622

  6. Papudesi, B.N., Malayala, S.V., & Regina, A.C. (2023). Xylazine toxicity. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2024 January. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK594271/

  7. Perrone J, Haroz R, D’Orazio J, et al. National Institute on Drug Abuse Clinical Trials Network Meeting Report: Managing Patients Exposed to Xylazine-Adulterated Opioids in Emergency, Hospital and Addiction Care Settings. Annals of Emergency Medicine. 2024;84(1):20-28. doi:10.1016/j.annemergmed.2024.01.041

  8. Philadelphia Department of Public Health Substance Use Prevention and Harm Reduction (December 8, 2022), Health update: Xylazine (tranq) exposure among people who use substances in Philadelphia. Retrieved from hip.phila.gov/document/3154/PDPH-HAN_Update_13_Xylazine_12.08.2022.pdf/

  9. The White House Executive Office of the President Office of the National Drug Control Policy (July 2023): The Fentanyl Adulterated or Associated with Xylazine Response Plan (FAAX) Plan. Retrieved from: FENTANYL-ADULTERATED-OR-ASSOCIATED-WITH-XYLAZINE-EMERGING-THREAT-RESPONSE-PLAN-Report-July-2023.pdf (whitehouse.gov)

  10. U.S. Food and Drug Administration (2022). FDA alerts health care professionals of risks to patients exposed to xylazine in illicit drugs. Retrieved from: FDA alerts health care professionals of risks to patients exposed to xylazine in illicit drugs | FDA

  11. Vega, I. L., Griswold, M. K., & O’Gurek, D. T. (2023). The role of xylazine in the overdose crisis. American Family Physician, 108(3), 229–230.

 

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