Disclaimer to the On-line Edition
This Manual has been designed for use in the NICU at London Health Sciences Centre (LHSC), London, Ontario, Canada, and represents clinical practice at this institution. The information contained within the Manual may not be applicable to other centres. If users of this Manual are not familiar with a drug, it is recommended that the official monograph be consulted before it is prescribed and administered. Any user of this information is advised that the contributors, Editor and LHSC are not responsible for any errors or omissions, and / or any consequences arising from the use of the information in this Manual.



  • Adjunct medication used in the management of neonatal abstinence syndrome that results from opioid exposure


  • Chronic opioid exposure suppresses catecholamine release in various parts of the brain. Abrupt discontinuation of the opioid results in a rebound increase in the release of catecholamines. This surge of catecholamine release is responsible for the onset of withdrawal symptoms (NAS)
  • At low doses, clonidine preferentially stimulates a2-adrenergic receptors, located presynaptically in the midbrain and medulla. The resulting effect is a decrease in the release of catecholamines and an attenuation of many of the symtoms of NAS.
  • Well absorbed after oral administration
  • Highly lipid soluble
  • 40-60% is eliminated unchanged by kidneys

Adverse Effects

  • Hypotension
  • Bradycardia / tachcardia
  • Rebound hypertension if abruptly discontinued
  • Sodium and water retention
  • Constipation


  • Some studies gradually increased doses over 1 to 2 days to begin therapy, and tapered doses by 0.25 mcg/kg every 6 hours to discontinue (or by 25% of the total daily dose every other day).
  • However, clonidine has also been started and stopped abruptly with no adverse effects.
  • Adjust doses in patients with renal insufficiency

Special Note

  • Three deaths in the clonidine group were reported by the only prospective RCT on Clonidine vs Placebo (Agthe 2009). The deaths occurred after hospital discharge but before 2 months of age. Excluding the death from methadone overdose (homicide), the other two deaths were believed to be due to myocarditis and SIDS, respectively. All deaths were reported to the Food and Drug Administration and the Data Safety and Monitoring Board, which deemed the deaths not likely attributed to clonidine exposure, and the study was allowed to continue.


  • 0.5 - 1 mcg/kg, given orally every 4-6 hours
  • Much higher doses (0.5 to 3 mcg/kg/h) have been used as a continuous infusion (Reference # 6)
  • Adequate clinical trials to establish an efficacious and safe dose still are required


  • 10 mcg/mL  ORAL suspension prepared by Pharmacy Services
  • Keep suspension in refrigerator, shake well before using


  1. Agthe AG, Kim GR, Mathias KB et al: Clonidine as an Adjunct Therapy to Opioids for Neonatal Abstinence Syndrome: A Randomized Controlled Trial. Pediatrics (2009) 123, e849-e856.
  2. Hoder LE, Leckman JF, Poulsen J et al: Clonidine Treatment of Neonatal Narcotic Abstinence Syndrome. Psychiatry Research (1984) 13, 243-251.
  3. Leikin JB, Mackendrick WP, Maloney GE et al: Use of clonidine in the prevention and management of neonatal abstinence syndrome. Clinical Toxicology (2009) 47, 551-555.
  4. McClain BC, Probst LA, Pinter E et al: Intravenous Clonidine Use in a Neonate Experiencing Opioid-Induced Myoclonus. Anesthesiology (2001) 95, 549-550.
  5. Roberts RJ: Drug Therapy in Infants, W.B. Saunders, Toronto, 1984.
  6. Esmaeili A Keinhorst AK, Schuster T, Schlosser R, Bastanier C. Treatment of neonatal abstinence syndrome with clonidine and chloral hydrate. Acta Paediatrica (2009) Oct, 1-6 (on line)

Monograph prepared by : Heather Bannerman, Pharmacy Student
Revised by : David Knoppert, MScPhm
Reviewed by : Dr H Roukema
December 2009

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