Clonidine Toxicity


Practice Essentials

Clonidine is a central alpha-agonist that is used as an antihypertensive agent. Other reported clinical uses include treatment of opiate and alcohol withdrawal[1] and control of atrial fibrillation with a rapid ventricular rate. It is also used for the following:

At therapeutic doses (0.2-0.9 mg/d), clonidine is commonly associated with adverse effects such as dry mouth, sedation, dizziness, and constipation. While generally safe, at toxic doses clonidine can cause serious cardiopulmonary instability and central nervous system (CNS) depression in children and adults.

Clonidine is available in a weekly transdermal patch (Catapres TTS: 0.1 mg, 0.2 mg, or 0.3 mg/d, with each patch containing 2.5 mg, 5 mg, and 7.5 mg of clonidine, respectively) and in tablet form (Catapres: 0.1 mg, 0.2 mg, and 0.3 mg; Combipres includes 15 mg of chlorthalidone diuretic). An ophthalmic solution is occasionally used in the treatment of glaucoma.


Clonidine is an imidazole derivative and was first used as a nasal decongestant. Decongestants containing tetrahydrozoline, also an imidazole derivative, can result in the same signs and symptoms as clonidine poisoning when ingested, especially in children.

Clonidine acts primarily as a presynaptic CNS alpha2-agonist, stimulating receptors in the nucleus tractus solitarii of the medulla oblongata. This inhibits sympathetic outflow, which results primarily in a reduction of sympathetically mediated vasoconstriction, cardiac inotropy, and chronotropy.

Clonidine also has peripheral alpha1-agonist activity, which may produce transient vasoconstriction and hypertension early in overdose when peripheral drug levels may be transiently higher than levels in the CNS.

Clonidine is rapidly absorbed from the gastrointestinal tract and has excellent CNS penetration because of lipid solubility. Peak plasma concentrations are reached 3-5 hours after a single oral dose. Dermal application may take several days to reach steady state levels. No known pharmacologically active metabolites exist. Plasma half-life is 12-16 hours, with the antihypertensive effects occurring within 30-60 minutes of ingestion. Clonidine is excreted unchanged in the urine and is metabolized by the liver.



United States

In the 2016 Annual Report of the American Association of Poison Control Centers' National Poison Data System, 5351 single exposures to clonidine were reported. Of those, 3504 were unintentional toxicities and 106 were reported as an adverse reaction.[4]


Mortality is rare with a small number of reported deaths. Morbidity, in terms of cardiorespiratory and CNS dysfunction, generally tends to be more severe in young persons than in adults.

Of the 5351 reported toxic exposures to clonidine in 2016, 3858 were treated in a health care facility. Of this subset of patients, 972 had no significant outcome, 1192 had minor effects, 1748 had moderate morbidity, and 139 had major morbidity. No deaths were reported.[4]


Of the 5351 reported toxic exposures to clonidine in 2016, 1760 were in patients younger than 6 years, 2106 were in patients 6-19 years old, and 1315 were in patients 20 years of age and older.[4]


While elucidating the amount and timing of the clonidine ingestion is helpful, in practice, signs and symptoms guide therapy. Always suspect other co-ingestants and screen appropriately.

Children are particularly susceptible to toxic reaction from small doses (ie, normal adult therapeutic doses) of clonidine.

The Catapres TTS patch appears similar to a small Band-Aid or sticker, and a child could pull the patch off a sleeping caretaker. Several case reports document patches detaching spontaneously from a sleeping parent in a bed shared with a child and subsequently adhering to the child with resultant toxicity. In cases of possible clonidine toxicity involving children, always question family, friends, and emergency medical services (EMS) as to whether a child may have had access to clonidine.

Irritability may be noted.

Three patients who were receiving long-term treatment with intrathecal clonidine experienced a clonidine overdose because of inadvertent extravasation during the refilling procedure. All three patients experienced loss of consciousness and severe systemic hypertension that required aggressive parenteral treatment. Inadvertent injection of clonidine into the subcutaneous pocket rather than into the reservoir is rare, but it is very dangerous because the drug cannot be retrieved and massive doses are involved.[5]


Symptoms develop rapidly (usually within 30-60 min) postingestion and may resemble an opioid overdose with miosis, bradycardia, respiratory depression, and coma. From a differential standpoint, comatose-appearing children with clonidine toxicity may awaken and be intermittently lucid when subjected to vigorous stimuli (eg, physical, verbal), whereas patients with opioid overdoses subjected to the same stimuli may awaken but are obtunded.

Symptoms tend to be relatively more severe in pediatric patients. Toxic presentations also may include hypotension, hypertension, mydriasis, hypothermia, ileus, hypotonia, hyporeflexia, intermittent apnea, atrioventricular (AV) nodal heart block, and seizures.

With significant ingestions, patients usually present with bradycardia.[6] Associated hypotension may be severe and last up to 24 hours. Hypertension is less common and usually more transient.

Hypothermia has been reported but is usually mild. Patients may present with CNS depression, which may range from mild drowsiness (common) to coma. Baseline mental status usually returns within 24-48 hours of ingestion.

Hyporeflexia may develop, and seizures may occur.

Dysrhythmias may occur and include AV nodal block, Wenckebach, and tachycardia. Pallor and cool extremities have been reported.


Respiratory depression is common, especially in children, and may require endotracheal intubation. Respiratory failure usually occurs within 1-2 hours of ingestion. Ataxic breathing may be observed, and patients may experience periods of apnea.

Approach Considerations

Clonidine levels have not been shown to correlate with toxicity and should not be routinely drawn. Measure electrolyte and glucose levels to screen for anion gap acidosis or hypoglycemia.

Serum toxicology screen may be useful if the patient is not responding to standard measures; has significant symptoms and a co-ingestion is suspected; or is comatose. It may also be useful if a specific drug level is desired. Acetaminophen levels should be obtained if overdose is suspected.

Other studies to consider include the following:

Prehospital Care

Provide aggressive supportive care because patients may rapidly decompensate. Address airway, breathing, and circulation (ABCs) as usual. Intravenous access with crystalloid and pressor support with dopamine may be necessary.

If a clonidine patch is present on the skin, remove it and wash the exposed area. Initiate standard naloxone therapy and blood glucose checks.

Continuous electrocardiographic (ECG) monitoring should carry over to the emergency department (ED).

Prehospital ipecac syrup administration is contraindicated.

Emergency Department Care

Focus initial treatment on the ABCs. Clonidine toxicity can cause serious respiratory depression and apnea requiring immediate endotracheal intubation and mechanical ventilation. Once the airway is secure, place the patient on continuous ECG, blood pressure, and oxygen saturation monitoring. Place at least one large-bore IV line. Consider central venous pressure (CVP) monitoring in patients who are markedly hypotensive.

Clonidine toxicity can cause serious respiratory depression and apnea requiring immediate endotracheal intubation and mechanical ventilation.

Hypotension is very common with clonidine toxicity; initially treat the patient with aggressive crystalloid infusion. If aggressive volume resuscitation fails to raise blood pressure, consider pressors such as dopamine and epinephrine. Maintain good urine output because clonidine is excreted at least 50% unchanged in the urine.

Bradycardia, either sinoatrial (SA) nodal or AV nodal, has been reported with clonidine toxicity. Atropine is the first-rate drug of choice. Consider dopamine if atropine fails with SA nodal, first-degree, or Mobitz I AV nodal block; however, in Mobitz II and third-degree AV nodal block, atropine is only temporizing until definitive pacing is initiated.

Transcutaneous pacing is quicker to initiate, but causes the patient more discomfort than transvenous pacing. Consider transvenous pacing in patients with massive ingestions who have third-degree AV nodal block.

Hypertension may occur initially from peripheral alpha1-agonist activity and vasoconstriction. This hypertension is usually transient and does not require treatment; if hypertension is severe, symptomatic, and prolonged, treatment with a short-acting agent such as intravenous nitroprusside can be considered.

Administer activated charcoal by mouth or nasogastric tube for clonidine toxicity in a 1-g/kg dose (standard for toxic ingestions). If significant CNS depression exists, intubate before administering activated charcoal to prevent aspiration. The clinician should be aware that even intubated patients are at risk of activated charcoal aspiration. Lavage is controversial; yet consider it if ingestion is significant and occurred less than an hour before arrival.

Naloxone (Narcan) may treat clonidine toxicity. It improves the mental status of adults and children who have ingested toxic amounts of clonidine; this, however, has not been universal and naloxone can cause hypotensive and hypertensive responses.[7] Naloxone can also has been reported to cause severe hypertension.[8]

The American Academy of Pediatrics[9] recommends a dose of naloxone of 0.1 mg/kg for infants and children up to age 5 years or weighing 20 kg. Children older than 5 years or weighing more than 20 kg may be given 2 mg of naloxone. Adults with isolated clonidine toxicity may be given 2 mg doses of naloxone, titrated to effect. The clinician should be aware that naloxone administration in chronic opioid users can precipitate withdrawal with consequent vomiting and risk of aspiration.

Provide symptomatic and supportive care, the main therapy for clonidine toxicity. Passively warm patients who have hypothermia. Most comas resolve with supportive measures.

Two case reports document yohimbine reversal of clonidine toxic states.[10] Yohimbine is a central alpha2-adrenergic antagonist with effects that directly oppose clonidine, making it a theoretically useful antidotal agent.[10]


Unless the treating physician has extensive experience with acute poisonings or if significant toxicity manifests, contacting a poison control center for advice and feedback is reasonable. A formal toxicology team may provide valuable input.

Medication Summary

In general, treat with supportive care. Administer activated charcoal to all patients at risk for aspiration after intubation. Temporary support for symptomatic cardiovascular effects of clonidine also may be necessary.

Dopamine (Intropin)

Clinical Context:  DOC in patients with clonidine toxicity who remain hypotensive after IVF. Stimulates adrenergic and dopaminergic receptors. Hemodynamic effect is dependent on dose. Lower doses predominantly stimulate dopaminergic receptors that, in turn, produce renal and mesenteric vasodilation. Higher doses produce cardiac stimulation and renal vasodilation.

Atropine IV/IM (Atropair)

Clinical Context:  Vagolytic for patients with bradycardia (eg, SA or AV nodal block).

Doses < 0.5 mg can produce a paradoxical reaction.

Naloxone (Narcan)

Clinical Context:  Absolute benefits are unproven and rates of success vary. Consider a drip if significant improvement results.

Activated charcoal (Liqui-Char)

Clinical Context:  Emergency treatment in poisoning caused by drugs and chemicals. Network of pores present in activated charcoal adsorbs 100-1000 mg of drug per gram of charcoal. Does not dissolve in water.

For maximum effect, administer within 30 min of ingesting poison.

Further Outpatient Care

Patients with suspected clonidine ingestion may be discharged if they remain asymptomatic for 4-6 hours and have normal vital signs.

Obtain a psychiatric evaluation before discharge for patients with suspected intentional ingestion.

Further Inpatient Care

Admit significantly symptomatic patients with clonidine toxicity to the intensive care unit (ICU).

A ward admission on a monitor is probably reasonable for minimal symptoms if the patient has been observed for several hours with improvement or without worsening. Remember that patients demonstrating clonidine toxicity, secondary to transdermal exposure, may experience a prolonged period of symptoms from a prolonged half-life secondary to a "depot" effect in the subdermal tissues.


Transfer patients with clonidine toxicity if the potential benefits outweigh the risks.


Patients should be taught how to safely discard the clonidine patch and prevent exposure of children.


Prognosis is generally good for patients who present early and have had prompt and proper treatment.

Patient Education

Children may be easily affected by relatively small doses of clonidine. Educating patients about the importance of keeping clonidine and all drugs out of children's reach is critical.

For patient education resources, see the Drug Overdose Center and Poisoning - First Aid and Emergency Center, as well as Poisoning, Drug Overdose, Activated Charcoal, and Poison Proofing Your Home.


David Riley, MD, MSc, RDMS, RDCS, RVT, RMSK, Assistant Clinical Professor of Medicine, Director of Emergency Ultrasonography and Ultrasound Research, Attending Physician, Department of Emergency Medicine, Columbia University Medical Center, New York Presbyterian Hospital

Disclosure: Nothing to disclose.

Specialty Editors

John T VanDeVoort, PharmD, Regional Director of Pharmacy, Sacred Heart and St Joseph's Hospitals

Disclosure: Nothing to disclose.

John G Benitez, MD, MPH, Associate Professor, Department of Medicine, Medical Toxicology, Vanderbilt University Medical Center; Managing Director, Tennessee Poison Center

Disclosure: Nothing to disclose.

Chief Editor

Michael A Miller, MD, Clinical Professor of Emergency Medicine, Medical Toxicologist, Department of Emergency Medicine, Texas A&M Health Sciences Center; CHRISTUS Spohn Emergency Medicine Residency Program

Disclosure: Nothing to disclose.

Additional Contributors

Edward A Michelson, MD, Associate Professor, Program Director, Department of Emergency Medicine, University Hospital Health Systems of Cleveland

Disclosure: Nothing to disclose.


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