Summary:
- Medetomidine is an animal sedative used in veterinary medicine that is 100-200x more potent than xylazine. In 2025, it began to appear in the illicit fentanyl supply nationally and has been detected in fentanyl circulating in Jefferson and Clallam Counties and surrounding areas.
- Providers should be aware of the possibility of medetomidine involvement in treating overdose and withdrawals and adapt responses when indicated.
- Responding to opioid overdoses involving medetomidine should prioritize breathing over responsiveness.
- Use of low-dose naloxone is preferred for overdose reversal.
- Medetomidine withdrawal syndrome is a severe consequence of substance use often requiring admission to an intensive care unit for treatment.
- Triaging patients with suspected medetomidine withdrawal requires early initiation of alpha-2-agonist and long-acting opioid treatments and frequent monitoring.
- Medetomidine use has not been shown to be associated with wounds.
What is Medetomidine?
Similar to xylazine, medetomidine is a synthetic alpha-2 agonist sedative used in veterinary medicine. In human medicine, medetomidine is most similar to dexmedetomidine (Precedex®) and clonidine. Overdoses involving medetomidine are associated with prolonged sedation that requires adapting overdose response protocols to prioritize breathing over responsiveness. Medetomidine can produce a severe withdrawal syndrome that is characterized by tachycardia, severe hypertension, waxing and waning alertness, tremor, and intractable nausea and vomiting.
Medetomidine Overdose
Signs & Symptoms
- Heavy sedation – persistent despite naloxone administration
- Respiratory depression
- Bradycardia
- Hemodynamic instability – may be hypotensive or severely hypertensive
Treatment Recommendations
With overdoses involving medetomidine, sedation is common even after naloxone is administered. Overdose response should:
- Focus on breathing & respiration versus responsiveness
- Manage sedation after breathing is restored
- Administer only the amount of naloxone needed to restore breathing in order to avoid precipitating withdrawal symptoms
Caring for Patients who Use Fentanyl:
- Educate on the possibility of medetomidine in the drug supply
- Encourage drug testing – medetomidine test strips are available at Jefferson County Public Health
- Encourage safer use practices (not using alone, carrying naloxone)
- Connect to treatment support when ready
Medetomidine Withdrawal
Medetomidine withdrawal syndrome is severe and can be life-threatening. In a recent MMWR, 91% of patients hospitalized for medetomidine withdrawal required ICU admission. Presentations of medetomidine withdrawal syndrome have been associated with end-organ damage, such as non-ST elevation myocardial infarction (NSTEMI) and Posterior Resolving Encephalopathy Syndrome (PRES). The onset of signs and symptoms have been described as beginning abruptly with rapid progression within hours of last use. Providers have described symptoms peaking within 18-36 hours.
Signs & Symptoms
- Tachycardia
- Severe hypertension
- Nausea & vomiting
- Anxiety, restlessness & diaphoresis
- Tremor/myoclonic jerking that can appear seizure-like
Treatment Recommendations
- Use IM injections/patches vs oral medications if possible
- Early initiation of alpha-2-agonists, primarily clonidine, adding tizanidine or guanfacine if needed
- Early and rapid initiation of long-acting opioids for treatment of fentanyl withdrawal (methadone preferred)
- More intensive patient & vital monitoring for the initial 24 hours
- Obtain EKG to assess QTc
- Symptom management: olanzapine is preferred for anxiety, restlessness and nausea/vomiting. For pain, short acting opioids & ketamine are preferred alongside acetaminophen & NSAIDs.
- Screen for medical comorbidities that can complicate treatment such as:
- heart, lung, or liver disease
- seizure disorders; or
- psychiatric disorders
- Screen for substance use disorders other than opioid related that may complicate withdrawals, such as alcohol, sedatives, or stimulants.
Further Resources:
Philadelphia Department of Public Health Division of Substance Use Prevention & Harm Reduction: Medetomidine Health Update (June 10, 2025): https://hip.phila.gov/document/5444/PDPH-HAN-SUPHR-Medetomidine-06.10.2025_1Zu1OZ4.pdf/
Allegheny County Health Department: Substance Brief – Medetomidine (August 2025): https://www.med.unc.edu/fammed/nctac/wp-content/uploads/sites/1256/2025/08/ACHD-Medetomidine-Brief-August-2025.pdf
CDC Morbidity and Mortality Weekly Report – Severe Medetomidine Withdrawal, Philadelphia
CDC Morbidity and Mortality Weekly Report – Opioid Overdoses involving Medetomidine, Chicago
Adapted with permission from Clallam County Public Health