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Front. Pharmacol. | doi: 10.3389/fphar.2018.00148

When the safe alternative is not that safe: tramadol prescribing in children

 Frédérique Rodieux1, Laszlo Vutskits2, 3,  Klara M. Posfay-Barbe4, Walid Habre5, Valérie Piguet1, Jules A. Desmeules1 and  Caroline F. Samer1*
  • 1Department of Anesthesiology, Pharmacology and Intensive care, Geneva University Hospitals (HUG), Switzerland
  • 2Department of Anesthesiology, Pharmacology and Intensive care, Geneva University Hospitals (HUG), Switzerland
  • 3Department of Basic Neuroscience, Université de Genève, Switzerland
  • 4Department of Pediatrics, Geneva University Hospitals (HUG), Switzerland
  • 5Department of Anesthesiology, Pharmacology and Intensive care, Geneva University Hospitals (HUG), Switzerland

Children represent a vulnerable population in which management of nociceptive pain is complex. Drug responses in children differ from adults due to age-related differences. Moreover, therapeutic choices are limited by the lack of indication for a number of analgesic drugs due to the challenge of conducting clinical trials in children. Furthermore the assessment of efficacy as well as tolerance may be complicated by children’s inability to communicate properly. According to the World Health Organisation, weak opioids such as tramadol and codeine, should be used in addition to paracetamol and ibuprofen for moderate nociceptive pain in both children and adults. However, codeine prescription has been restricted for the last 5 years in children because of the risk of fatal overdoses linked to the variable activity of CYP2D6 which bioactivates codeine. Tramadol has been considered a safe alternative to codeine. However, it is well established that tramadol pharmacodynamic opioid effects, efficacy and safety, are also largely influenced by CYP2D6 activity. For this reason, the Food and Drug Administration recently released a boxed warning regarding the use of tramadol in children. To provide safe and effective tramadol prescription in children, a personalized medicine approach, with dose adaptation according to CYP2D6 activity, would certainly be the safest method. We therefore recommend this approach in children requiring chronic or recurrent nociceptive pain treatment with tramadol. In case of acute inpatients nociceptive pain management, prescribing tramadol at the minimal effective dose, in a dosage form adapted to the child and after clear instructions given to the parents, seems reasonable based on current data. In all other situations, morphine should be preferred for moderate to severe nociceptive pain conditions.

Keywords: Tramadol, Codeine, Opioids, Children, Pharmacogenetics, CYP2D6, Safety, Pain

Received: 20 Nov 2017; Accepted: 13 Feb 2018.

Edited by:

Edoardo Spina, Università degli Studi di Messina, Italy

Reviewed by:

Janet K. Coller, University of Adelaide, Australia
Diego M. Fornasari, Università degli Studi di Milano, Italy  

Copyright: © 2018 Rodieux, Vutskits, Posfay-Barbe, Habre, Piguet, Desmeules and Samer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Caroline F. Samer, Geneva University Hospitals (HUG), Department of Anesthesiology, Pharmacology and Intensive care, Genève, Switzerland,