OVERDOSE RESPONSE CENTER
Partner Information Bulletin #2026-03
Clinical guidance: Medetomidine
Overview
Delaware’s Overdose System of Care, with support from the Overdose Response Center, is sharing the following clinical recommendations for addressing medetomidine, currently being seen across the state’s medical systems.
• Medetomidine has been increasingly detected in Delaware’s illicit drug supply and is expanding throughout the state.
• The following pages provide targeted clinical guidance to a variety of settings (outpatient, ED, in hospital).
Background
Medetomidine is an alpha-2-adrenergic agonist medication approved for veterinary use only.
• In early 2024 medetomidine was detected in the street drug supply in Philadelphia, followed by a rapid increase in the number and severity of overdoses in Philadelphia and northern Delaware.
• Unlike opioid-only overdoses, medetomidine causes profound bradycardia and sedation that does not respond to naloxone, though naloxone remains vital for the reversal of concurrent opioid-induced respiratory depression.
• Severe withdrawal syndromes have caused large increases in hospital admissions, including in the Philadelphia and northern Delaware areas.
Medetomidine Clinical Syndromes: Overdose/Toxicity
Signs and Symptoms:
• Bradycardia (often 40-55/min), Hypotension, Significant Sedation (often lasting 4-6+ hours)
Monitoring:
• Closely monitor airway, breathing, blood pressure, heart rate, and pulse oximetry.
Treatment:
• Naloxone to reverse the opioid/fentanyl-related respiratory depression.
Breathing and pulse oximetry typically improve, but sedation & bradycardia continue.
• Typically, supportive care, including airway/vital sign monitoring, and IV fluids if needed.
• Vasopressors, atropine, or transcutaneous pacing are typically not necessary.
• Sedation and bradycardia typically begin to improve in 4-6 hour
Medetomidine Clinical Syndromes: Withdrawal
Important to note:
– Medetomidine withdrawal syndrome starts earlier than opioid withdrawal.
– After resolution of overdose/toxicity symptoms, medetomidine withdrawal may rapidly worsen within hours.
– Complications of severe medetomidine withdrawal include encephalopathy, myocardial injury, acute kidney injury, and vomiting-related aspiration or esophageal injury.
Signs/Symptoms:
– Hypertension (often in the 180-200+ systolic range) – Tachycardia (often 130+/min)
– Shaking/tremor (severe, can be confused for seizure) – Decreased verbal response and catatonic-appearance
Monitoring:
– Closely monitor airway, breathing, blood pressure, heart rate, and pulse oximetry.
– Evaluate for signs of complications or end-organ damage due to severe withdrawal.
Treatment Guidance:
– General suggestions for treatment below are based on published data and regional expert opinion.
– These suggestions may be considered in producing facility-specific policies or protocols.
– Patient care must include an individualized assessment and plan based on patient-specific risks, allergies, and potential medication interactions or contraindications.
In the Outpatient Setting
Mild/Early Medetomidine Withdrawal and able to tolerate oral medications
Treat Symptoms:
Nausea, vomiting, diarrhea, pain, anxiety, etc.
Treat Medetomidine Withdrawal:
Alpha-2-agonists:
• Clonidine 0.2-0.3 mg PO every 6-8 hours. Tapering off clonidine over at least 2 weeks is recommended for continued control of withdrawal symptoms.
NOTE: Consider potential risks of clonidine treatment (such as hypotension or bradycardia), however, patients using medetomidine typically have high alpha-2-agonist tolerance.
• Tizanidine 2-4 mg PO every 8 hours, as needed for muscle cramps/spasm associated with medetomidine withdrawal.
Severe Medetomidine Withdrawal -or- Rapid worsening of symptoms
Call 911 or refer to the emergency department.
Treat Opioid Withdrawal:
Start Medications for Opioid Use Disorder (MOUD): Buprenorphine-Naloxone (Suboxone®), if possible, or refer to an opioid treatment program for methadone treatment.
In the Emergency Department
Mild/Early Medetomidine Withdrawal and able to tolerate oral medications
Treat Symptoms:
Nausea, vomiting, diarrhea, pain, anxiety, etc.
Treat Medetomidine Withdrawal:
Alpha-2-agonists:
• Clonidine 0.3-0.6 mg PO every 6-8 hours.
• Clonidine transdermal patch 0.3-0.6 mg/24h patch every week.
NOTE: Oral clonidine and transdermal clonidine patch may be used together as transdermal patch has prolonged onset of action (48+hours). Some facilities recommend higher oral clonidine doses or alternative alpha-2-agonist medications (such as guanfacine).
• Tizanidine 4 mg PO every 6-8 hours, as needed for muscle cramps/spasm associated with medetomidine withdrawal.
Treat Opioid Withdrawal:
• Start Medications for Opioid Use Disorder (MOUD): Buprenorphine-Naloxone (Suboxone®) or methadone, if possible.
• Opioid agonists (such as oxycodone or hydromorphone) are NOT indicated in the treatment of mild symptoms.
Severe Medetomidine Withdrawal and unable to tolerate oral medications
Treatments from “Mild/Early” plus,
If continued severe signs/symptoms, such as hypertension, tachycardia, shaking/tremor, and intractable vomiting, THEN:
Treat Medetomidine Withdrawal:
Start Dexmedetomidine (Precedex) infusion:
• Recommended higher starting dose of at least 0.5 mcg/kg/hr, with rapid titration.
• Consider loading dose of 0.5-1 mcg/kg over 20-30 minutes for severe withdrawal.
• Monitor per facility-specific policy (such as RASS and COWS scoring)
RASS of 0 is typically recommended for titration of dexmedetomidine.
• Typical maximum dose is 1.5 mcg/kg/hr, however, there is some evidence for higher doses (facility and level-of-care dependent).
• Continuous telemetry monitoring.
Treat Opioid Withdrawal:
• Start Medications for Opioid Use Disorder (MOUD): Buprenorphine-Naloxone (Suboxone®) or methadone, if possible.
• Patients with combined severe opioid withdrawal and medetomidine withdrawal often need full opioid agonists to help control symptoms. Consider hydromorphone 2-4 mg IV and evaluate response.
In the Hospital
Initially, continue care from “In the Emergency Department” section
Level of care based on facility-specific policy. Some health systems have developed successful policies for stepdown/intermediate level of care if adequate monitoring is available.
• Continuous telemetry monitoring .
• Monitor per facility-specific policy (such as RASS and COWS scoring)
RASS of 0 is typically recommended for titration of dexmedetomidine.
Dexmedetomidine (Precedex) infusion weaning:
• Should be slowly weaned. Recommendations include maintaining RASS of 0 during weaning.
• Goal of introducing oral alpha-2-agonists when able to tolerate PO medications.
• Continue clonidine transdermal patch.
Treat Opioid Withdrawal:
• Start Medications for Opioid Use Disorder (MOUD): Buprenorphine-Naloxone (Suboxone®) or methadone, if possible.
• Opioid agonists (such as oxycodone or hydromorphone) are NOT first-line in the treatment of mild opioid withdrawal.
Discharge Planning Care
Focus on starting MOUD and arranging post-hospitalization plan for ongoing care
Continue alpha-2-agonist (such as clonidine) after discharge from the hospital to prevent return of withdrawal symptoms.
• Alpha-2-agonist (clonidine) should be tapered over at least 2 weeks after discharge.
• Example post-hospitalization clonidine taper:
Days 1–5: Clonidine 0.2 mg q8h
Days 6–10: Clonidine 0.1 mg q8h
Days 11–14: Clonidine 0.1 mg q12h, then stop
Treat Opioid Withdrawal:
• Continue MOUD (buprenorphine or methadone) after hospitalization and direct linkage to ongoing OUD care.
Additional specific clinical questions, please contact: OEMS@delaware.gov
Contact: ORC@delaware.gov
Approved: 20 February 2026
Brent Waninger, ORC Director