Illicit Medetomidine Use with Fentanyl

Medetomidine is a non-opioid veterinary anesthetic drug and a synthetic alpha-2-adrenoceptor agonist that is not approved for human use. Increasingly, it’s being used with illicitly manufactured fentanyl, xylazine (another, similar, non-opioid, animal sedative), heroin, and other street drugs in several parts of the U.S.¹ Because it’s an emerging adulterant, the Centers for Disease Control is closely monitoring it.²

Medetomidine is more potent than xylazine. It may produce longer-lasting sedation, has approximately 200-fold higher potency, and is 10 times more selective.³ Several media reports about overdoses from cities including St. Louis, Pittsburgh, San Francisco, Philadelphia, Toronto, and Chicago, have appeared in the last few months. The fentanyl-medetomidine combination has triggered a new wave of overdoses this year, prompting states to issue alerts.^4,5 With the rising number of medetomidine-induced seizures in the U.S., it has become an urgent public health issue, and we aim to raise awareness among hospitalists regarding this growing crisis.

The illegal use of medetomidine was initially discovered in Maryland but has been found in toxicology specimens of suspected opioid overdose patients in multiple states, including Missouri, Colorado, Maryland, Pennsylvania, and California. In December 2023, the Center for Forensic Science Research & Education issued an alert that medetomidine was detected in overdoses in St. Louis and clandestine laboratory seizures in Ohio, Florida, and Canada.⁶ The emergence of medetomidine across the country appears to be following the same path as xylazine and fentanyl, beginning in the Northeast, spreading to the South, and moving westward. This pattern indicates that the use of medetomidine as an adulterant will likely increase in the future and is likely to be encountered in the illicit fentanyl supply.

Adverse effects and testing

Medetomidine use among humans is not well described, and most of the data currently is based on veterinary studies. Prolonged sedation, peripheral vasoconstriction, bradycardia, and hypotension have been reported adverse effects in humans.^1,3  Peripheral vasoconstriction caused by medetomidine may impact wounds and healing, as seen in xylazine. It is unclear if the wounds caused by medetomidine are similar to those that occur with xylazine.⁷ In veterinary literature, it has been reported that medetomidine causes vasoconstriction, which could impact wound healing or wounds caused by intravenous drug use. Other symptoms include several adverse gastrointestinal effects, such as vomiting, decreased gastric motility, and bloody diarrhea.⁷ The risk of extreme drowsiness and sedation is increased when medetomidine and dexmedetomidine are used in combination with high-potency opioids, benzodiazepine-related drugs, and xylazine. Testing for medetomidine is challenging because of the lack of available testing techniques. Unlike xylazine, testing strips are not yet available to detect medetomidine. Different states use methods ranging from the Rapid Analysis of Drugs, or RAD, program to Community Drug Checking and Rapid Drug Analysis and Research, or RaDAR.^1,5 These programs focus on rapidly identifying illicit substances in high-risk individuals.

Management of overdose and withdrawals

The first step for hospitalists in responding to a medetomidine drug overdose is to do essential life support, similar to any other overdose. Since medetomidine is a non-opioid sedative, its effects are not reversed by naloxone, which is the first response to drug overdose

While atipamezole or yohimbine can reverse the effects of medetomidine, similar to xylazine, these medications are not approved for use in humans.⁸ Atipamezole and yohimbine can cause harmful alpha-2-agonist withdrawal symptoms, including hypertension, agitation, and tachycardia.⁹ Patients who suffer from severe bradycardia and hypotension due to medetomidine can benefit from evidence-based medicine, including airway management and cardiopulmonary support. Medetomidine, like xylazine, can cause prolonged sedation. This emphasizes the importance of protecting the airway, which may be compromised with prolonged sedation.

The symptoms of medetomidine withdrawal are not well-known, but they may be similar to those of dexmedetomidine, with hypertension, tachycardia, and agitation. For patients who are experiencing withdrawal symptoms from opioids, clonidine is both an effective treatment in the management of dexmedetomidine withdrawal and an adjunctive treatment for opioid withdrawal management. If the patient is hemodynamically stable but still experiencing withdrawal symptoms after optimizing opioid agonist treatment, consider using clonidine as early as possible in the withdrawal management process and titrating the dose.

Conclusion

Medetomidine’s increased prevalence in illicit drug supplies, especially when combined with fentanyl, poses an acute public health threat. Medetomidine’s potency as a powerful sedative compound magnifies overdose risks with severe consequences, including prolonged sedation and compromised airway management, further compounded by the absence of human-specific antidotes. This has prompted healthcare providers and public health officials to develop strategies aimed at decreasing harm from overdose incidents by simultaneously raising awareness, improving testing methods, and developing effective public health strategies against them to address this emerging crisis effectively. 

Dr. Sood

Dr. Dhillon

Dr. Sood is a hospitalist at Banner Gateway Medical Center in Gilbert, Ariz., affiliated with MD Anderson Cancer Center in Houston. Dr. Dhillon is an assistant medical director and hospitalist with Adfinitas Health at the University of Maryland Medical Center, in Glen Burnie, Md.

References

1. Kariisa M, O’Donnell J, et al. Illicitly manufactured fentanyl-involved overdose deaths with detected xylazine—United States, January 2019-June 2022. MMWR Morb Mortal Wkly Rep. 2023;72(26):721-7.
2. Schwarz ES, Buchanan J, et al. Notes from the field: detection of medetomidine among patients evaluated in emergency departments for suspected opioid overdoses — Missouri, Colorado, and Pennsylvania, September 2020–December 2023. MMWR Morb Mortal Wkly Rep. 2024;73:672–674.
3. Scheinin H, Virtanen R, et al. Medetomidine—a novel alpha 2-adrenoceptor agonist: a review of its pharmacodynamic effects. Prog Neuropsychopharmacol Biol Psychiatry. 1989;13(5):635-51
4. Department of Public Health City of Philadelphia. Health alert. Philadelphia Public Health Department website. https://hip.phila.gov/document/4421/PDPH-HAN-0441A-05-13-24.pdf/. Published May 13, 2024. Accessed October 6, 2024.
5. New York State Office of Addiction Services and Supports. Another potent sedative, medetomidine, now appearing in illicit drug supply. NYS OASAS website.  https://oasas.ny.gov/advisory-may-31-2024. Published May 31, 2024. Accessed October 6, 2024.
6. The Center for Forensic Science Research & Education. Medetomidine rapidly proliferating across USA—implicated in recreational opioid drug supply & causing overdose outbreaks. CFSRE website. https://www.cfsre.org/nps-discovery/public-alerts/medetomidine-rapidly-proliferating-across-usa-implicated-in-recreational-opioid-drug-supply-causing-overdose-outbreaks. Published May 20, 2024. Accessed October 6, 2024.
7. Department of Public Health City of Philadelphia. Recommendations for caring for individuals with xylazine-associated wounds. Philadelphia Public Health Department website. https://hip.phila.gov/document/4148/Recommendations_for_Caring_for_People_with_Xylazine-Associated_Wounds_1.12.pdf/. Published January 8, 2024. Accessed October 6, 2024.
8. Papich MG Medetomidine hydrochloride. In: Papich MG, ed. Saunders Handbook of Veterinary Drugs 4th ed. Philadelphia:W.B. Saunders;2016:481-483.
9. Knapp T, DiLeonardo O, et al. Dexmedetomidine withdrawal syndrome in children in the PICU: systematic review and meta-analysis. Pediatr Crit Care Med. 2024;25(1):62-71.