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Increasing presence of xylazine in heroin and/or fentanyl deaths, Philadelphia, Pennsylvania, 2010-2019 - Fentanyl & xylazine have replaced heroin in "street heroin"
  Of note, as fentanyl has largely replaced the heroin supply in Philadelphia, xylazine has been increasingly found in combination with fentanyl. Some evidence suggests that the combination of xylazine and fentanyl in humans may potentiate the desired effect of sedation and the adverse effects of respiratory depression, bradycardia and hypotension caused by fentanyl alone,1 comparable to the synergistic effects of combining benzodiazepines with heroin and/or fentanyl.7
Xylazine is an ⍺2-adrenergic agonist initially developed as an antihypertensive agent by Farbenfabriken Bayer AG (Leverkusen, Germany) in 1962, although severe hypotension and central nervous system (CNS) depression in early human clinical trials prevented its approval.1 The drug was reintroduced in the late 1960s and early 1970s as a veterinary medication for sedation and analgesia1 and is currently an unscheduled, approved drug by the US Food and Drug Administration for use as a sedative in horses, dogs, cats, deer, and elk.2 Pharmacokinetic and pharmacodynamic data primarily exist in animal species, with human data currently sparse.
Among 2019 decedents with positive detections for xylazine, 100% were positive for fentanyl.
The Philadelphia Department of Public Health says 90% of fentanyl samples tested in 2021 contained xylazine.3
Veterinary tranquilizer does not respond to opioid-reversing drugs like naloxone, contributing to an increase in overdose deaths.
people who use fentanyl/heroin indicated an interest to test their drug for the presence of xylazine prior to use
In the event of a suspected xylazine overdose, experts recommend giving the opioid overdose reversal medication naloxone because xylazine is frequently combined with opioids.9 However, because xylazine is not an opioid, naloxone does not address the impact of xylazine on breathing.1,3,8 Because of this, experts are concerned that a growing prevalence of xylazine in the illicit opioid supply may render naloxone less effective for some overdoses.1,2,10 Emergency medical services should always be alerted to a suspected overdose. Learn more about stopping overdose from the CDC
Repeated xylazine use is also associated with skin ulcers, abscesses, and related complications.1,4,11 People report using xylazine or xylazine-containing drugs by injecting, snorting, swallowing, or inhaling.3,4 https://nida.nih.gov/research-topics/xylazine
A total of 210 xylazine-associated deaths were reported during the study period. Xylazine-associated deaths increased throughout the study period; incidence peaked during October 2021. https://www.cdc.gov/mmwr/volumes/71/wr/mm7113a3.htm
in May 2022, a baggie sold as fentanyl for injection in Providence, Rhode Island, was found to contain fentanyl, acetylfentanyl, acrylfentanyl, para-fluorofentanyl, xylazine, tramadol, methadone, phenacetin, ketamine, acetaminophen, lidocaine, nicotine, and caffeine.4 Naloxone will work to restore breathing from opioid-induced respiratory depression, but will not reverse the effects of xylazine or other sedatives. This may affect overdose response counseling provided by pharmacists as the focus of naloxone administration should be to restore breathing.
Reports from active drug users state that xylazine, the veterinary tranquilliser, has been increasing in the illicit drug supply in Philadelphia. To describe trends and characteristics of unintentional deaths from heroin and/or fentanyl overdose with xylazine detections occurring in Philadelphia, Pennsylvania, the Philadelphia Department of Public Health analysed data on deaths from unintentional heroin and/or fentanyl overdose from the Philadelphia Medical Examiner's Office over a 10-year period (2010-2019). Xylazine went from being detected in less than 2% cases of fatal heroin and/or fentanyl overdose between 2010 and 2015 to 262 (31%) of the 858 fatal heroin and/or fentanyl overdose cases in 2019. Currently, information is limited on the presence of xylazine in continental United States. Xylazine's association with adverse outcomes in other locations indicates that potential health consequences should also be monitored in the USA. Whenever possible, jurisdictions should consistently test for xylazine.
Among 2019 decedents with positive detections for xylazine, 100% were positive for fentanyl, 10% were positive for heroin, 7% were positive for pharmaceutical opioids such as oxycodone, 6% were positive for methadone, 12% were positive for methamphetamine, 28% were positive for benzodiazepines and 53% were positive for cocaine (table 1). Evidence of injection was more prevalent among heroin and/or fentanyl decedents who were positive for xylazine than for those who were not (p<0.0001) (table 1). https://injuryprevention.bmj.com/content/27/4/395


FDA warns xylazine-adulterated opioid overdoses on the rise
Illicit drugs contaminated with Xylazine have exploded in popularity, leading to a nationwide increase in overdose deaths. The drug is increasingly being cut with opioids like fentanyl to lengthen the duration of the high. The danger to human patients, the FDA warned in a statement, is that nonopioid xylazine does not respond to overdose-reversal drugs like naloxone that are designed to counter the effects of opioid overdose.1 Xylazine is an FDA-approved nonopioid veterinary tranquilizer, used as a sedative and pain reliever for animals. It is not approved for use in humans. On the illicit drug market, xylazine is known as "tranq" or "tranq dope." The drug itself produces powerful sedative effects in people similar to that of opioids, such as heroin, fentanyl, and oxycodone "oxy." When combined with opioids, xylazine increases the duration of the user's euphoric effects.
1. FDA alerts health care professionals of risks to patients exposed to xylazine in illicit drugs. News release. US Food and Drug Administration. November 8, 2022. Accessed December 16, 2022.
2. Johnson J, Pizzicato L, Johnson C, Viner K. Increasing presence of xylazine in heroin and/or fentanyl deaths, Philadelphia, Pennsylvania, 2010-2019. Inj Prev. 2021;27(4):395-398. doi:10.1136/injuryprev-2020-043968 3. Xylazine (Tranq). Philadelphia Department of Public Health. Accessed December 16, 2022. https://www.substanceusephilly.com/tranq
4. Friedman J, Montero F, Bourgois P, et al. Xylazine spreads across the US: A growing component of the increasingly synthetic and polysubstance overdose crisis. Drug Alcohol Depend. 2022;233:109380. doi:10.1016/j.drugalcdep.2022.109380
5. Kariisa M, Patel P, Smith H, Bitting J. Notes from the Field: Xylazine Detection and Involvement in Drug Overdose Deaths - United States, 2019. MMWR Morb Mortal Wkly Rep. 2021;70(37):1300-1302. Published 2021 Sep 17. doi:10.15585/mmwr.mm7037a4
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