Xylazine Adulteration in Illicit Fentanyl: A Threat to Public Health.

Background: Xylazine-adulterated fentanyl (FAAX) is a critical public health concern in the United States (US), and the White House Office of National Drug Control Policy designated FAAX as an emerging drug threat in April 2023. Between 2020-2021, fatal xylazine-positive overdoses increased by 100-1127% depending on geographic region in the US. Objectives: This narrative review informs pharmacists about the clinical concerns, potential treatment strategies, and harm reduction approaches directed at FAAX. The objective is to provide pharmacists with the knowledge necessary to contribute to public health efforts in addressing this crisis. Results: Xylazine is commonly found as an adulterant in illicit drug combinations with fentanyl. Significant hypotension, and respiratory and CNS depression are associated with xylazine toxicity, and these effects may be synergistic with opioids. Standard naloxone doses are ineffective for xylazine toxicity, and there is no FDA-approved antidote for xylazine overdose in humans. Chronic use may lead to physiological dependence, withdrawal symptoms, and severe skin ulcerations. Pharmacists are crucial in addressing this crisis through patient education, advocating for testing and treatment, and promoting harm reduction measures. Conclusion: Xylazine and FAAX pose a substantial threat to public health. The synergistic effects of opioids increase the risk of fatal overdoses, highlighting the need for effective harm-reduction strategies. A comprehensive approach involving healthcare professionals, law enforcement, policymakers, and community organizations is required to address this public health issue, and pharmacists have an active role in mitigating the drug threat of FAAX.