Grand RoundsEltrombopag-Induced Acute Liver Failure in a Pediatric Patient: A Pharmacokinetic and Pharmacogenetic AnalysisMarano, Marco MD*; Serafinelli, Jessica MD†; Cairoli, Sara PharmSciD‡; Martinelli, Diego MD, PhD§; Pisani, Mara MD¶; Palumbo, Giuseppe MD, PhD║; Cefalo, Maria G. MD║; Cecchetti, Corrado MD, PhD*; Di Nardo, Matteo MD*; Falvella, Felicia S. BiolSciD**; Goffredo, Bianca M. BiolSciD‡Author Information *Pediatric Intensive Care Unit, Bambino Gesù Children Hospital IRCSS; †Division of Immunology and Infectious Diseases, University-Hospital Pediatric Department (DPUO), Bambino Gesù Children Hospital IRCSS, “Tor Vergata University”; ‡Laboratory of Analytical Biochemistry, Bambino Gesù Children Hospital IRCCS; §Division of Metabolism, Bambino Gesù Children Hospital IRCCS; ¶DEA, IRCCS Bambino Gesù Children Hospital IRCSS; ║Department of Pediatric Hematology/Oncology, Bambino Gesù Children Hospital IRCCS, Rome, Italy; and **Unit of Clinical Pharmacology, Department of Laboratory Medicine, ASST Fatebenefratelli-Sacco, Milan, Italy. Correspondence: Jessica Serafinelli, MD, Division of Immunology and Infectious Diseases, University-Hospital Pediatric Department (DPUO), Bambino Gesù Children Hospital IRCSS, “Tor Vergata University,” Piazza Sant'Onofrio 4, 00165 Rome, Italy (e-mail: [email protected]). The authors declare no conflict of interest. Therapeutic Drug Monitoring: August 2018 - Volume 40 - Issue 4 - p 386-388 doi: 10.1097/FTD.0000000000000522 Buy Metrics Abstract Eltrombopag is an oral thrombopoietin receptor agonist approved for the treatment of patients with chronic idiopathic thrombocytopenic purpura (ITP), who are more than 1 year old, and show poor response to first-line therapy. ITP is a hematological disorder characterized by isolated thrombocytopenia in the absence of secondary causes or disorders. Eltrombopag is generally well tolerated in the pediatric population; therefore, therapeutic drug monitoring (TDM) is not usually performed in clinical practice. We presented the case study of a 3-year-old girl with chronic ITP. She arrived in the pediatric intensive care unit with acute liver failure due to eltrombopag toxicity despite taking the standard drug dosage. A very high eltrombopag plasma concentration, indicating drug toxicity, was found through TDM. The patient also carried the allelic variations that are involved in drug metabolism [CYP2C8 and UDP glucuronosyltransferase (UGT) 1A1 (UGT1A1)] and drug cellular transportation [ABCG2 (ATP-binding cassette G2)]. This observation highlights the importance of using TDM and pharmacogenetic approaches to manage patients' unusual complications associated with standard pharmacological treatment regimens. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.