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2026.03 – Medetomidine Clinical Guidance

Overdose Response Center

Partner Information Bulletin

Clinical Guidance: Medetomidine

Bulletin Number: 2026-03

Contact: ORC@delaware.gov
Approved: February 20, 2026
Approved By: Brent Waninger, ORC Director

Overview

The Delaware Overdose System of Care, with support from the Overdose Response Center (ORC), developed these clinical recommendations to address the increasing presence of medetomidine in Delaware’s illicit drug supply.

The guidance is intended for multiple clinical settings, including outpatient care, emergency departments, and inpatient hospital care.

Background

  • Medetomidine is an alpha-2 adrenergic agonist approved only for veterinary use.
  • It was first identified in the Philadelphia street drug supply in early 2024 and was followed by a rapid increase in overdose events in Philadelphia and northern Delaware.
  • Unlike opioid-only overdoses, medetomidine can cause profound bradycardia and sedation that do not respond to naloxone, although naloxone remains important for reversing opioid-induced respiratory depression.
  • Severe withdrawal syndromes have resulted in significant increases in hospital admissions in the region.

Medetomidine Overdose/Toxicity

Common Signs and Symptoms

  • Bradycardia (often 40–55 beats per minute)
  • Hypotension
  • Significant sedation, often lasting four to six hours or longer

Monitoring

Patients should be closely monitored for:

  • Airway
  • Breathing
  • Blood pressure
  • Heart rate
  • Pulse oximetry

Treatment Considerations

  • Administer naloxone to reverse opioid- or fentanyl-related respiratory depression.
  • Breathing and oxygenation often improve after naloxone, while sedation and bradycardia may persist.
  • Supportive care, including airway monitoring, vital sign monitoring, and intravenous fluids as needed, is typically appropriate.
  • Vasopressors, atropine, or transcutaneous pacing are generally not required.
  • Sedation and bradycardia usually begin improving within four to six hours.

Medetomidine Withdrawal

Important Considerations

  • Withdrawal often begins earlier than opioid withdrawal.
  • Symptoms may worsen rapidly after overdose symptoms resolve.
  • Severe withdrawal may lead to encephalopathy, myocardial injury, acute kidney injury, aspiration, or esophageal injury from vomiting.

Possible Signs and Symptoms

  • Hypertension (often systolic blood pressure of 180–200 mmHg or higher)
  • Tachycardia (often above 130 beats per minute)
  • Severe shaking or tremors that may resemble seizures
  • Decreased verbal responsiveness or a catatonic appearance

Monitoring

Monitor:

  • Airway and breathing
  • Blood pressure
  • Heart rate
  • Pulse oximetry
  • Evidence of end-organ damage or other complications

Clinical treatment should always be individualized based on patient-specific risks, allergies, contraindications, and medication interactions.

Outpatient Setting

Mild or Early Withdrawal

Symptomatic treatment may include management of:

  • Nausea
  • Vomiting
  • Diarrhea
  • Pain
  • Anxiety

Suggested withdrawal management includes:

  • Clonidine 0.2–0.3 mg orally every 6–8 hours, with gradual tapering over at least two weeks
  • Tizanidine 2–4 mg orally every 8 hours as needed for muscle cramps or spasms

For opioid withdrawal, consider initiating medications for opioid use disorder (MOUD), such as buprenorphine-naloxone, or referral for methadone treatment.

Severe Withdrawal or Rapid Worsening

Patients with severe symptoms should be referred to the emergency department or instructed to call 911.

Emergency Department Guidance

Mild or Early Withdrawal

Treatment recommendations include:

  • Symptom management
  • Clonidine 0.3–0.6 mg orally every 6–8 hours
  • Weekly clonidine transdermal patch (0.3–0.6 mg/24 hours)
  • Tizanidine 4 mg orally every 6–8 hours as needed

For opioid withdrawal:

  • Consider buprenorphine-naloxone or methadone.
  • Full opioid agonists are generally not indicated for mild symptoms.

Severe Withdrawal

For severe withdrawal with inability to tolerate oral medications:

  • Consider dexmedetomidine (Precedex) infusion beginning at approximately 0.5 mcg/kg/hour with rapid titration.
  • Loading doses and higher infusion rates may be considered based on facility protocols.
  • Continuous telemetry monitoring is recommended.
  • Patients with combined severe opioid and medetomidine withdrawal may require additional opioid management, such as hydromorphone, based on clinical judgment.

Treatment should follow facility-specific policies and individualized patient assessment.

Inpatient Hospital Care

Ongoing Care

Continue emergency department management while:

  • Monitoring according to facility protocols
  • Using continuous telemetry
  • Gradually weaning dexmedetomidine infusions
  • Transitioning patients to oral alpha-2 agonists when tolerated
  • Continuing clonidine transdermal therapy as appropriate

For opioid withdrawal:

  • Initiate medications for opioid use disorder (buprenorphine or methadone) when appropriate.
  • Full opioid agonists are generally not first-line therapy for mild opioid withdrawal.

Discharge Planning

Recommended discharge considerations include:

  • Continuing alpha-2 agonist therapy (such as clonidine) after hospitalization to reduce recurrence of withdrawal symptoms
  • Tapering clonidine over at least two weeks
  • Example taper:
    • Days 1–5: Clonidine 0.2 mg every 8 hours
    • Days 6–10: Clonidine 0.1 mg every 8 hours
    • Days 11–14: Clonidine 0.1 mg every 12 hours, then discontinue
  • Continuing medications for opioid use disorder and ensuring linkage to ongoing treatment services after discharge.

Additional Information

For additional clinical questions, the bulletin directs providers to contact:

OEMS@delaware.gov