Ceritinib-associated hyperglycemia in the Japanese Adverse Drug Event Report Database

J Diabetes Investig. 2020 May;11(3):726-730. doi: 10.1111/jdi.13168. Epub 2019 Nov 29.

Abstract

Genetic rearrangements of anaplastic lymphoma kinase contribute to the pathogenesis of non-small-cell lung cancer; the anaplastic lymphoma kinase inhibitor, ceritinib, is widely used, as it is effective even in patients with non-small-cell lung cancer resistant to other anaplastic lymphoma kinase inhibitors. Although a case of possible ceritinib-induced hyperglycemia was reported, the association of ceritinib with hyperglycemia remains to be investigated. Disproportionality analysis was carried out using the Japanese Adverse Drug Event Report database, which contains all pharmacovigilance data based on spontaneous reports of adverse events between April 2004 and November 2018 to the Pharmaceuticals and Medical Devices Agency. The reporting odds ratio of ceritinib for hyperglycemia was 2.25 (95% confidence interval [CI] 1.24-4.08], whereas those of crizotinib and alectinib were 0.07 (95% CI 0.01-0.40) and 0.94 (95% CI 0.30-2.94), respectively. Among reported events without antidiabetes agent use, the reporting odds ratio of ceritinib was still 2.54 (95% CI 1.27-5.12). Thus, the possibility of hyperglycemia should be carefully monitored in patients receiving ceritinib.

Keywords: Anaplastic lymphoma kinase; Ceritinib; Drug-induced hyperglycemia.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Databases, Factual
  • Female
  • Humans
  • Hyperglycemia / chemically induced*
  • Japan
  • Lung Neoplasms / drug therapy
  • Male
  • Odds Ratio
  • Protein Kinase Inhibitors / adverse effects*
  • Pyrimidines / adverse effects*
  • Sulfones / adverse effects*

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Sulfones
  • ceritinib