Near-fatal tramadol cardiotoxicity in a CYP2D6 ultrarapid metabolizer

Abstract

International audienc

Severe Tramadol Overdoses in Children: A Case Series Admitted to Paediatric Intensive Care Unit

“…A few cases of ultra-rapid metabolizers can be found in the literature, both for the paediatric population [3] and for adults [24,25]. In 6 of our cases, we had a history of drug overdose but in one case (case n°6), no clear explanation was found after parental questioning.…”

PharmGKB summary

“…CYP2D6 plays a pivotal role in the pharmacokinetics and analgesic efficacy of tramadol. Several reduced or none functional CYP2D6 alleles as well as alleles with multiple gene copies have significant impacts on clinical outcome in patients under tramadol medication [22,24,27,33,45,51–55]. Pharmacokinetic studies have shown that the impact of CYP2D6 phenotypes on tramadol pharmacokinetics was similar after single oral, multiple oral, or intravenous administrations [33,52,55].…”

“…Severe life-threatening adverse events were reported in two case reports. One patient with renal impairment carrying the CYP2D6 gene duplication experienced respiratory depression [45] and another UM developed a near-fatal cardiotoxicity, in both cases because of tramadol use [51]. …”

Pharmacogenetics and Metabolism: Past, Present and Future

“…On the other hand, loss of therapeutic efficacy at standard doses can also be observed in UMs since the drug metabolization occurs at a fast rate (Davis & Homsi 2001). Finally, UM may also present either improved therapeutic efficacy or more frequently severe adverse effects, due to a higher rate of toxic metabolites formation (Kirchheiner et al 2008;Elkalioubie et al 2011). …”