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Rodieux F, Vutskits L, Posfay-Barbe KM, et al. When the Safe Alternative Is Not That Safe: Tramadol Prescribing in Children. Front Pharmacol. 2018;9:148doi: 10.3389/fphar.2018.00148.
Rodieux, F., Vutskits, L., Posfay-Barbe, K. M., Habre, W., Piguet, V., Desmeules, J. A., & Samer, C. F. (2018). When the Safe Alternative Is Not That Safe: Tramadol Prescribing in Children. Frontiers in pharmacology, 9148. https://doi.org/10.3389/fphar.2018.00148
Rodieux, Frédérique, et al. "When the Safe Alternative Is Not That Safe: Tramadol Prescribing in Children." Frontiers in pharmacology vol. 9 (2018): 148. doi: https://doi.org/10.3389/fphar.2018.00148
Rodieux F, Vutskits L, Posfay-Barbe KM, Habre W, Piguet V, Desmeules JA, Samer CF. When the Safe Alternative Is Not That Safe: Tramadol Prescribing in Children. Front Pharmacol. 2018 Mar 05;9:148. doi: 10.3389/fphar.2018.00148. eCollection 2018. PMID: 29556194; PMCID: PMC5844975.
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Front Pharmacol. 2018 Mar 05;9:148. doi: 10.3389/fphar.2018.00148. eCollection 2018.

When the Safe Alternative Is Not That Safe: Tramadol Prescribing in Children.

Frontiers in pharmacology

Frédérique Rodieux, Laszlo Vutskits, Klara M Posfay-Barbe, Walid Habre, Valérie Piguet, Jules A Desmeules, Caroline F Samer

Affiliations

  1. Division of Clinical Pharmacology and Toxicology, Department of Anesthesiology, Pharmacology and Intensive Care, Geneva University Hospitals, University of GenevaGeneva, Switzerland.
  2. Department of Anesthesiology, Pharmacology and Intensive Care, Geneva University Hospitals, University of GenevaGeneva, Switzerland.
  3. Department of Basic Neuroscience, Faculty of Medicine, University of GenevaGeneva, Switzerland.
  4. Division of Anesthesiology, Unit for Pediatric Anesthesia, Children's Hospitals of Geneva, Geneva University Hospitals, University of GenevaGeneva, Switzerland.
  5. Pediatric Infectious Diseases Unit, Department of Pediatrics, Children's Hospital of Geneva, Geneva University Hospitals, University of GenevaGeneva, Switzerland.
  6. Anesthesiological Investigations Unit, Department of Anesthesiology, Pharmacology and Intensive Care, Geneva University Hospitals, University of GenevaGeneva, Switzerland.
  7. School of Pharmaceutical Sciences, University of Geneva, University of LausanneGeneva, Switzerland.

PMID: 29556194 PMCID: PMC5844975 DOI: 10.3389/fphar.2018.00148

Abstract

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 Organization, weak opioids such as tramadol and codeine, may 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 cytochrome P450 (CYP) 2D6 which bioactivates codeine. Even though tramadol has been considered a safe alternative to codeine, it is well established that tramadol pharmacodynamic opioid effects, efficacy and safety, are also largely influenced by CYP2D6 activity. For this reason, the US 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 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 child appropriate dosage form and after clear instructions are given to the parents, remains reasonable based on current data. In all other situations, morphine should be preferred for moderate to severe nociceptive pain conditions.

Keywords: CYP2D6; children; codeine; opioids; pain; pharmacogenetics; safety; tramadol

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