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Emerging Threat of Xylazine in Combination with Fentanyl

Louisiana Department of Health Reporting the Emerging Threat of Xylazine in Combination with Fentanyl

The Louisiana Opioid Surveillance Initiative (LOSI) is tracking an increase in the number of drug overdose deaths involving 

Xylazine is a non-opioid, central nervous system depressant that can cause drowsiness, amnesia, slowed breathing, reduced heart rate, and dangerously low blood pressure.

  Also known as “tranq” or “tranq dope,” it is a veterinary tranquilizer that is 

 approved for human use. Nationally, xylazine has been reported as an adulterant in the illicit drug supply and has been detected in an increasing number of overdose deaths.

Xylazine or drugs that contain xylazine can be injected, snorted, swallowed, or inhaled.

 Xylazine is most often found mixed with heroin and fentanyl.

 Stimulants such as methamphetamine and cocaine have also been combined with xylazine.

 Because xylazine is often found in combination with other sedating drugs like opioids, there is an increased risk for overdose or death. Often people who are exposed to xylazine are unaware that it is in their drug supply when they are ingesting it. Unfortunately, opioid antagonists like naloxone are ineffective in reversing the sedative effects of xylazine, increasing its lethality. However, as mentioned above, xylazine is often times used in combination with opioids and therefore using naloxone can still be of benefit in those cases.

LOSI collects data on fatal drug overdoses from coroners, drug seizures, and toxicology testing results. LOSI analyzed fatal overdoses deaths in Louisiana occurring from 2018 to 2022. Xylazine-involved deaths are defined as deaths with xylazine included in the primary or secondary cause of death. 

Xylazine was involved in 39 overdose deaths in 2021, an 86% increase from 2020. 

Xylazine as a contributor to overdose deaths is likely under-reported due to non-specific causes of death used in the death records database, such as “multi-drug toxicity” or “cardiac arrest due to polysubstance abuse.”

In 2019, LOSI began providing comprehensive toxicology testing for coroners through the Overdose Data to Action grant funds. In 2021, 4% of all post-mortem toxicology tests were positive for xylazine. This represents an increase greater than 300% from 2019, when 0.9% of test were positive for xylazine. Post-mortem toxicology results for 2022 are still outstanding so these data are preliminary.

Designation as an emerging national drug threat

On April 12, 2023, the White House Office of National Drug Control Policy (ONCDP) officially designated fentanyl adulterated or associated with xylazine as an emerging threat to the United States. This designation was made because xylazine combined with fentanyl is being sold illicitly and is associated with significant and rapidly worsening negative health consequences, including fatal overdoses and severe health outcomes. 

Injection use of xylazine has been associated with severe, necrotic skin ulcerations and other skin complications. These ulcerations may develop at the site of injection or in areas of the body away from the site of injection. 

 These wounds can be severe and are distinctly different from other soft-tissue infections, such as cellulitis and abscesses often associated with injection drug use.

Because xylazine is a such a potent sedative, people who use xylazine may become unconscious for long periods of time and fall asleep in certain positions that may compromise their airway or put them at increased risk for pressure ulcers, compartment syndrome  

  The sedative effects of xylazine also puts individuals at increased risk for physical harm, sexual assault, and robberies.

Repeated exposure to xylazine may result in dependence. Withdrawal symptoms such as agitation and severe anxiety may occur when the usual doses of the drug are decreased or discontinued.

Once ingested, xylazine has a rapid onset and can last 8 hours or longer depending on the dose.

   Initially, people become sleepy, their heart rate and blood pressure will decrease. With high doses, people may become comatose with small pupils and hypothermia. Breathing may decrease or even stop. These signs and symptoms looks very similar to an opioid overdose.

The symptoms of xylazine use and opioid use are similar, making it difficult to differentiate whether an individual has used one or both substances. 

If an overdose from a xylazine-containing drug occurs, administer naloxone.

because xylazine is often combined with fentanyl

. Naloxone will not reverse the effects of xylazine, but it will reverse the effects of fentanyl and other opioids that have been mixed with xylazine. The person may remain unresponsive if xylazine is involved. After naloxone is administered, call for help and seek assistance from emergency medical personnel.  

Provide rescue breathing, oxygen administration, and airway management if able and equipped. 

Inform emergency medical personnel of the possibility of a xylazine-involved overdose.

Health care professionals should consider potential xylazine exposure when patients appear to have an opioid overdose with small pupils, not breathing well, unresponsive, without responding to naloxone and have a very low heart rate (30-40 beats per minute) and low blood pressure. In these situations, health care professionals should provide supportive measures, secure the airway, and support breathing. Atropine or low dose epinephrine can be administered to improve the heart rate and blood pressure; blood pressure may be increased using fluids or a pressor, such as norepinephrine (Levophed), if needed. 

  Healthcare providers can consider screening for xylazine using appropriate tests if available; note that xylazine is currently not tested for in the common drugs of abuse panels. Additionally, health care professionals who see patients with severe, necrotic skin ulcerations should consider repeated xylazine exposure as part of the differential diagnosis. Finally, health care professionals caring for patients with opioid use disorder (OUD) should monitor patients for withdrawal symptoms not managed by traditional OUD treatments, as this may indicate xylazine withdrawal. 

Reducing the Harm for People Who Use Drugs

The illicit drug supply is unpredictable and there is not prevalent, readily available technology to test drugs for xylazine. It is safer to use when other people are present. People who feel safe and trust each other can use together, but take turns using in order to prevent simultaneous overdoses.

In case of an overdose, administer naloxone, give rescue breaths or CPR if trained and indicated, call 911 and monitor until breathing resumes. When exposed to xylazine, a person may remain sedated even after naloxone is administered and breathing has resumed.

Use sterile syringes and clean the site with an alcohol swab before every injection to prevent wound, ulcers, abscesses, and infections. Monitor site and seek medical attention in case of abscess and skin ulcers.

Contact a local harm reduction program or syringe services program for advice on safer use, safe use supplies, fentanyl test strips, naloxone, and/or assistance with abscesses or wound care. Note that fentanyl test strips only test for the presence of fentanyl; they do not test for the presence of xylazine.

Considering the increasingly dangerous illicit drug supply, LDH strongly recommends that individuals using drugs, their friends, and their families should have naloxone readily available.

Naloxone, commonly purchased as Narcan nasal spray, is life-saving medicine that can reverse an overdose by restoring normal breathing to a person experiencing opioid-induced respiratory depression. Naloxone is not harmful to anyone not overdosing. The Louisiana Department of Health has issued the 

, providing every individual in Louisiana with a prescription for the overdose reversal medication, which is available for purchase through most pharmacies and is covered by Louisiana Medicaid plans. Pharmacies will also provide information on how and when to administer this medicine. Naloxone is expected to be available as a fully over the counter medication in the coming months.

It is important for everyone to recognize the signs of an opioid overdose. These include:

Call 911 if any of these signs or symptoms of an opioid overdose are observed.

In Louisiana, “Good Samaritan Laws” provide legal protections to those who in good faith call for help or render assistance to an overdose victim (revised statute 14:403.10).

LDH has multiple resources and services available to individuals with substance use disorders and their loved ones.

[1] Ruiz-Colón K, Chavez-Arias C, Díaz-Alcalá JE, Martínez MA. 

Xylazine intoxication in humans and its importance as an emerging adulterant in abused drugs: A comprehensive review of the literature

. Forensic Sci Int. 2014;240:1-8. doi:10.1016/j.forsciint.2014.03.015

[2] Department of Justice Drug Enforcement Administration. (2022, October). 

The Growing Threat of Xylazine and its Mixture with Illicit Drugs

[4] Association of State and Territorial Health Officials. (2023, February 21). 

Xylazine: What Health Agencies Need to Know

[5] Food and Drug Administration. (2022, November 8). 

FDA Warns about the Risk of Xylazine Exposure in Humans

[6] White House Office of National Drug Control Policy. (2023, April 12). 

Biden Harris Administration Designates Fentanyl Combined with Xylazine as an Emerging Threat to the United States

[7] Compartment syndrome is an increase in pressure inside a muscle, which restricts blood flow and causes pain.

[8] Rhabdomyolysis occurs when damaged muscle tissue releases its proteins and electrolytes into the blood. These substances can damage the heart and kidneys and cause permanent disability or even death.

[9] Michigan Regional Poison Control Center. 