Tramadol intoxication in children: An emerging issue

Abstract

Background: Prescribing tramadol in children raises safety concerns. In Europe, tramadol is still approved and licensed for use in children over 1-3 years of age, depending on the country. In this context, the authors report a case of a tramadol overdose in a 5-year-old-child with a medical history of homozygous sickle cell disease.

Methods: Tramadol and M1 were quantified using liquid chromatography with a diode array detection method. CYP2D6 genotype was determined using a next generation sequencing platform (MISeq, Illumina).

Results: Tramadol and M1 were quantified in blood respectively at 5.48 and 1.32μg/mL at admission, at 0.77 and 0.35μg/mL 12hours later, and at 0.32 and 0.18μg/mL 20hours later. The patient was predicted as a CYP2D6 normal metabolizer (*35/*29).

Conclusion: One of the most important difficulties with the use of tramadol in children relates to its pharmacokinetic (PK) properties. Indeed, tramadol's PK is characterized by a great variability related to: (i) anatomical/physiological factors that impact the volume of distribution (Vd); (ii) CYP2D6 genetic polymorphisms. Considering such an issue is particularly relevant to prevent poisoning. In the reported case, the plasma elimination half-life was estimated at 6.3h, significantly more than those reported in 2-8 year-old children (about 3h). This discrepancy does not seem related to genetic polymorphisms but rather to the Vd. Indeed, the patient was predicted to be a CYP2D6 normal metabolizer (*35/*29). The case presented here highlights the risk associated with the tramadol use in children and emphasizes the importance of considering PK variability among this population. Such variability necessitates greater caution in prescribing tramadol in children and highlights the importance of therapeutic education for families of children treated with this painkiller.

Keywords: CYP2D6; Children; Overdose; Pharmacogenetics; Tramadol.