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Eltrombopag-Induced Acute Liver Failure in a Pediatric Patient: A Pharmacokinetic and Pharmacogenetic Analysis

Marco Marano1, Jessica Serafinelli2, Sara Cairoli3

  • 1Pediatric Intensive Care Unit, Bambino Gesù Children Hospital IRCSS.

Therapeutic Drug Monitoring
|April 24, 2018
PubMed

Insights

Therapeutic drug monitoring is crucial for pediatric idiopathic thrombocytopenic purpura (ITP) patients on eltrombopag. Genetic variations can lead to toxicity even at standard doses, necessitating personalized treatment approaches.

Area of Science:

  • Pharmacology
  • Genetics
  • Pediatrics

Background:

  • Eltrombopag, a thrombopoietin receptor agonist, treats chronic idiopathic thrombocytopenic purpura (ITP) in children unresponsive to initial therapies.
  • ITP is a bleeding disorder marked by low platelet counts without other identifiable causes.
  • Therapeutic drug monitoring (TDM) for eltrombopag is not standard practice in pediatric ITP due to its general tolerability.

Observation:

  • A 3-year-old girl with chronic ITP developed acute liver failure while on standard-dose eltrombopag.
  • Therapeutic drug monitoring revealed very high eltrombopag plasma concentrations, indicating toxicity.
  • The patient possessed genetic variations affecting drug metabolism (CYP2C8, UGT1A1) and transport (ABCG2).

Findings:

  • High eltrombopag plasma levels, indicative of toxicity, were detected via TDM.
  • The patient's genetic profile included variations in CYP2C8, UGT1A1, and ABCG2, influencing drug processing.
  • These factors likely contributed to the unexpected eltrombopag toxicity.

Implications:

  • This case underscores the importance of TDM in managing pediatric patients treated with eltrombopag.
  • Pharmacogenetic testing can identify individuals at risk for adverse drug reactions.
  • Personalized medicine approaches, incorporating TDM and pharmacogenetics, are vital for optimizing eltrombopag therapy and preventing toxicity in children.

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