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Clonidine and related imidazoline poisoning

Kevin C Osterhoudt, MD, MS
Section Editor
Michele M Burns, MD, MPH
Deputy Editor
James F Wiley, II, MD, MPH


The clinical features, evaluation, and management of clonidine and related imidazoline intoxication will be reviewed here. The clinical approach to the poisoned patient is discussed separately. (See "General approach to drug poisoning in adults" and "Approach to the child with occult toxic exposure".)


Clonidine, an alpha-2 adrenergic agonist, is a biochemical derivative of imidazoline that was initially introduced as a topical nasal decongestant over 40 years ago [1]. Subsequently, clonidine has been primarily utilized for its potent antihypertensive effect, but is used on- and off-label for a wide variety of indications. Guanfacine, and the antispasticity agent tizanidine, are also oral central alpha-2 adrenergic agonist medications that are being more commonly prescribed. Related imidazolines are found in topical eye and nose decongestants. In the United States, nearly 9000 calls regarding clonidine exposure are made annually to regional poison control centers, and serious clinical findings often requiring hospitalization are common [2-4]. As an example, among about 28,000 unintentional clonidine exposures in US children reported to poison control centers over 11 years, approximately 20 percent had moderate or major clinical effects [5].

Clonidine poisoning may occur from exploratory ingestion by young children, transdermal exposure from a clonidine patch, malicious drug administration, suicidal ingestion, or therapeutic error. Exploratory guanfacine exposures are also frequent, occurring in approximately 1500 US children annually [5].

Although clonidine exposure is frequently symptomatic in children, deaths due to pediatric exploratory ingestion of clonidine are rare [5,6].


Indications — Clonidine is indicated for the treatment of hypertension in adults, but is also used for anesthetic premedication, spinal anesthesia, opioid detoxification, alcohol withdrawal, smoking cessation, and amelioration of postmenopausal hot flashes [7-11]. In children, it is used in the treatment of attention deficit disorder with hyperactivity, refractory conduct disorder, and Tourette's syndrome [12-14]. In a mail survey of pediatricians, clonidine was also the second-most commonly prescribed (off-label) medication for treating sleep disturbances in children [15].  


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Literature review current through: Sep 2016. | This topic last updated: Oct 25, 2016.
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  1. Lowenstein J. Drugs five years later: clonidine. Ann Intern Med 1980; 92:74.
  2. Lai MW, Klein-Schwartz W, Rodgers GC, et al. 2005 Annual Report of the American Association of Poison Control Centers' national poisoning and exposure database. Clin Toxicol (Phila) 2006; 44:803.
  3. Bronstein AC, Spyker DA, Cantilena LR Jr, et al. 2011 Annual report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 29th Annual Report. Clin Toxicol (Phila) 2012; 50:911.
  4. Lovegrove MC, Mathew J, Hampp C, et al. Emergency hospitalizations for unsupervised prescription medication ingestions by young children. Pediatrics 2014; 134:e1009.
  5. Wang GS, Le Lait MC, Heard K. Unintentional pediatric exposures to central alpha-2 agonists reported to the National Poison Data System. J Pediatr 2014; 164:149.
  6. Klein-Schwartz W. Trends and toxic effects from pediatric clonidine exposures. Arch Pediatr Adolesc Med 2002; 156:392.
  7. Nishina K, Mikawa K, Uesugi T, et al. Efficacy of clonidine for prevention of perioperative myocardial ischemia: a critical appraisal and meta-analysis of the literature. Anesthesiology 2002; 96:323.
  8. Riordan CE, Kleber HD. Rapid opiate detoxification with clonidine and naloxone. Lancet 1980; 1:1079.
  9. Stanley KM, Worrall CL, Lunsford SL, et al. Experience with an adult alcohol withdrawal syndrome practice guideline in internal medicine patients. Pharmacotherapy 2005; 25:1073.
  10. Glassman AH, Stetner F, Walsh BT, et al. Heavy smokers, smoking cessation, and clonidine. Results of a double-blind, randomized trial. JAMA 1988; 259:2863.
  11. Clayden, JR, Bell, JW, Pellard, P. Menopausal flushing: double-blind trial of a non-hormonal medication. Br Med J 1974; 9:490.
  12. Connor DF, Fletcher KE, Swanson JM. A meta-analysis of clonidine for symptoms of attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 1999; 38:1551.
  13. Cohen DJ, Young JG, Nathanson JA, Shaywitz BA. Clonidine in Tourette's syndrome. Lancet 1979; 2:551.
  14. Hazell PL, Stuart JE. A randomized controlled trial of clonidine added to psychostimulant medication for hyperactive and aggressive children. J Am Acad Child Adolesc Psychiatry 2003; 42:886.
  15. Schnoes CJ, Kuhn BR, Workman EF, Ellis CR. Pediatric prescribing practices for clonidine and other pharmacologic agents for children with sleep disturbance. Clin Pediatr (Phila) 2006; 45:229.
  16. Chappell PB, Riddle MA, Scahill L, et al. Guanfacine treatment of comorbid attention-deficit hyperactivity disorder and Tourette's syndrome: preliminary clinical experience. J Am Acad Child Adolesc Psychiatry 1995; 34:1140.
  17. Gish EC, Miller JL, Honey BL, Johnson PN. Lofexidine, an {alpha}2-receptor agonist for opioid detoxification. Ann Pharmacother 2010; 44:343.
  18. Capraro AJ, Wiley JF 2nd, Tucker JR. Severe intoxication from xylazine inhalation. Pediatr Emerg Care 2001; 17:447.
  19. Muller AA, Osterhoudt KC, Wingert W. Heroin: what's in the mix? Ann Emerg Med 2007; 50:352.
  20. Rangan C, Everson G, Cantrell FL. Central alpha-2 adrenergic eye drops: case series of 3 pediatric systemic poisonings. Pediatr Emerg Care 2008; 24:167.
  21. Spiller HA, Bosse GM, Adamson LA. Retrospective review of Tizanidine (Zanaflex) overdose. J Toxicol Clin Toxicol 2004; 42:593.
  22. Lai Becker M, Huntington N, Woolf AD. Brimonidine tartrate poisoning in children: frequency, trends, and use of naloxone as an antidote. Pediatrics 2009; 123:e305.
  23. Eddy O, Howell JM. Are one or two dangerous? Clonidine and topical imidazolines exposure in toddlers. J Emerg Med 2003; 25:297.
  24. Romano MJ, Dinh A. A 1000-fold overdose of clonidine caused by a compounding error in a 5-year-old child with attention-deficit/hyperactivity disorder. Pediatrics 2001; 108:471.
  25. Oliver Rotellar JA, Sedano Monasterio E, Sabate de la Cruz J, Gausi Gene C. Clonidine in thousand-fold overdose. Lancet 1981; 1:1312.
  26. Al-Abri SA, Yang HS, Olson KR. Unintentional pediatric ophthalmic tetrahydrozoline ingestion: case files of the medical toxicology fellowship at the University of California, San Francisco. J Med Toxicol 2014; 10:388.
  27. Seger DL. Clonidine toxicity revisited. J Toxicol Clin Toxicol 2002; 40:145.
  28. Head GA, Gundlach AL, Musgrave IF. Recent advances in imidazoline receptor research: ligands--localization and isolation--signaling--functional and clinical studies. J Auton Nerv Syst 1998; 72:74.
  29. Talke PO, Caldwell JE, Richardson CA, Heier T. The effects of clonidine on human digital vasculature. Anesth Analg 2000; 91:793.
  30. Lowry JA, Brown JT. Significance of the imidazoline receptors in toxicology. Clin Toxicol (Phila) 2014; 52:454.
  31. Frisk-Holmberg M, Paalzow L, Edlund PO. Clonidine kinetics in man--evidence for dose dependency and changed pharmacokinetics during chronic therapy. Br J Clin Pharmacol 1981; 12:653.
  32. Dollery CT, Davies DS, Draffan GH, et al. Clinical pharmacology and pharmacokinetics of clonidine. Clin Pharmacol Ther 1976; 19:11.
  33. Lowenthal DT. Pharmacokinetics of clonidine. J Cardiovasc Pharmacol 1980; 2 Suppl 1:S29.
  34. MacGregor TR, Matzek KM, Keirns JJ, et al. Pharmacokinetics of transdermally delivered clonidine. Clin Pharmacol Ther 1985; 38:278.
  35. Lowry JA, Garg U. Serum concentrations in three children with unintentional tetrahydrozoline overdose. Clin Toxicol (Phila) 2011; 49:434.
  36. Osterhaudt KC. No sympathy for a boy with obtundation. Pediatr Emerg Care 2004; 20:403.
  37. Wiley JF 2nd, Wiley CC, Torrey SB, Henretig FM. Clonidine poisoning in young children. J Pediatr 1990; 116:654.
  38. Spiller HA, Klein-Schwartz W, Colvin JM, et al. Toxic clonidine ingestion in children. J Pediatr 2005; 146:263.
  39. Rapko DA, Rastegar DA. Intentional clonidine patch ingestion by 3 adults in a detoxification unit. Arch Intern Med 2003; 163:367.
  40. Killian CA, Roberge RJ, Krenzelok EP, Stonage CL. "Cloniderm" toxicity: another manifestation of clonidine overdose. Pediatr Emerg Care 1997; 13:340.
  41. Williams PL, Krafcik JM, Potter BB, et al. Cardiac toxicity of clonidine. Chest 1977; 72:784.
  42. Osterhoudt KC, Henretig FM. Sinoatrial node arrest following tetrahydrozoline ingestion. J Emerg Med 2004; 27:313.
  43. Kaddar N, Vigneault P, Pilote S, et al. Tizanidine (Zanaflex): a muscle relaxant that may prolong the QT interval by blocking IKr. J Cardiovasc Pharmacol Ther 2012; 17:102.
  44. Minns AB, Clark RF, Schneir A. Guanfacine overdose resulting in initial hypertension and subsequent delayed, persistent orthostatic hypotension. Clin Toxicol (Phila) 2010; 48:146.
  45. Hunyor SN, Bradstock K, Somerville PJ, Lucas N. Clonidine overdose. Br Med J 1975; 4:23.
  46. Wiley JF. Clonidine and related imidazoline derivatives. In: Haddad and Winchester's Clinical Management of Poisoning and Drug Overdose, 4th, Shannon MW, Burns MJ (Eds), Saunders Elsevier, Philadelphia 2007. p.1001.
  47. Maggi JC, Iskra MK, Nussbaum E. Severe clonidine overdose in children requiring critical care. Clin Pediatr (Phila) 1986; 25:453.
  48. Chyka PA, Seger D. Position statement: single-dose activated charcoal. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. J Toxicol Clin Toxicol 1997; 35:721.
  49. Juurlink DN. Activated charcoal for acute overdose: a reappraisal. Br J Clin Pharmacol 2016; 81:482.
  50. Horowitz R, Mazor SS, Aks SE, Leikin JB. Accidental clonidine patch ingestion in a child. Am J Ther 2005; 12:272.
  51. Kappagoda C, Schell DN, Hanson RM, Hutchins P. Clonidine overdose in childhood: implications of increased prescribing. J Paediatr Child Health 1998; 34:508.
  52. Tsze DS, Dayan PS. Treatment of guanfacine toxicity with naloxone. Pediatr Emerg Care 2012; 28:1060.
  53. Katar S, Taskesen M, Okur N. Naloxone use in a newborn with apnea due to tetrahydrozoline intoxication. Pediatr Int 2010; 52:488.
  54. Holmes JF, Berman DA. Use of naloxone to reverse symptomatic tetrahydrozoline overdose in a child. Pediatr Emerg Care 1999; 15:193.
  55. Ahmad SA, Scolnik D, Snehal V, Glatstein M. Use of naloxone for clonidine intoxication in the pediatric age group: case report and review of the literature. Am J Ther 2015; 22:e14.
  56. Gremse DA, Artman M, Boerth RC. Hypertension associated with naloxone treatment for clonidine poisoning. J Pediatr 1986; 108:776.
  57. Roberge RJ, McGuire SP, Krenzelok EP. Yohimbine as an antidote for clonidine overdose. Am J Emerg Med 1996; 14:678.
  58. Schieber RA, Kaufman ND. Use of tolazoline in massive clonidine poisoning. Am J Dis Child 1981; 135:77.
  59. Olsson JM, Pruitt AW. Management of clonidine ingestion in children. J Pediatr 1983; 103:646.
  60. Shannon M, Neuman MI. Yohimbine. Pediatr Emerg Care 2000; 16:49.
  61. Walton J, Byrum M, Shumaker A, Coury DL. Prolonged bradycardia and hypotension following guanfacine extended release overdose. J Child Adolesc Psychopharmacol 2014; 24:463.
  62. Nichols MH, King WD, James LP. Clonidine poisoning in Jefferson County, Alabama. Ann Emerg Med 1997; 29:511.