Low body surface area predicts hepatotoxicity of nintedanib in patients with idiopathic pulmonary fibrosis

Sci Rep. 2017 Sep 7;7(1):10811. doi: 10.1038/s41598-017-11321-x.

Abstract

After the commercialization of nintedanib in Japan, a high incidence of hepatotoxicity resulting in treatment interruption was noted in idiopathic pulmonary fibrosis (IPF) patients treated with nintedanib in our hospital. This study aimed to clarify the risk factors for hepatotoxicity of nintedanib. Sixty-eight consecutive cases of IPF newly treated with nintedanib at a dose of 150 mg twice daily from September 2015 to September 2016 were enrolled: 46 patients (67.6%) exhibited aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) elevation and 16 patients (23.5%) also had a Common Terminology Criteria for Adverse Events (CTCAE) grade ≥2. Body surface area (BSA) was significantly lower in the CTCAE grade ≥2 group than in another group. A multivariate logistic regression analysis showed that the association between BSA and AST/ALT elevation with CTCAE grade ≥2 was statistically significant. Eight of 10 patients who resumed nintedanib at a reduced dose of 100 mg twice daily after interruption due to hepatotoxicity did not again develop AST/ALT elevation. In conclusion, a low BSA was associated with hepatotoxicity of nintedanib at a dose of 150 mg twice daily. It would be a good option for patients with a small physique to start nintedanib at a dose of 100 mg twice daily and then increase if possible after confirming its safety.

MeSH terms

  • Aged
  • Alanine Transaminase / blood
  • Aspartate Aminotransferases / blood
  • Body Surface Area*
  • Chemical and Drug Induced Liver Injury / epidemiology*
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / adverse effects*
  • Enzyme Inhibitors / pharmacokinetics*
  • Female
  • Hospitals
  • Humans
  • Idiopathic Pulmonary Fibrosis / drug therapy*
  • Incidence
  • Indoles / administration & dosage
  • Indoles / adverse effects*
  • Indoles / pharmacokinetics*
  • Japan
  • Male
  • Risk Factors

Substances

  • Enzyme Inhibitors
  • Indoles
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • nintedanib