Apatinib-induced hyperammonemic encephalopathy

J Oncol Pharm Pract. 2020 Mar;26(2):465-470. doi: 10.1177/1078155219846253. Epub 2019 May 8.

Abstract

Apatinib is an orally administered small-molecule vascular endothelial growth factor receptor-2 inhibitor that has demonstrated encouraging anticancer activity across a broad range of malignancies, including gastric cancer, non-small-cell lung cancer, breast cancer, and hepatocellular carcinoma. We report a case of probable apatinib-induced hyperammonemic encephalopathy in a 69-year-old male. The patient received apatinib as targeted therapy for hepatocellular carcinoma and presented with acute confusion and hypersomnolence after four days of medication initiation. He showed improvement on drug withdrawal; then he resumed apatinib with a half dose and had a recurrence. Possible underlying mechanisms that include direct neuronal effect and antiangiogenic properties are discussed. We would like to draw attention to the potential risk of vascular endothelial growth factor receptor-tyrosine kinase inhibitors induced hyperammonemic encephalopathy even with a low dosage. Clinicians should be aware of any unexplained neurological syndrome after the initiation of apatinib in patients with hepatocellular carcinoma.

Keywords: Adverse drug reaction; apatinib; hepatic carcinoma; hyperammonemic encephalopathy.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Brain Diseases / chemically induced*
  • Brain Diseases / diagnosis
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / drug therapy
  • Humans
  • Hyperammonemia / chemically induced*
  • Hyperammonemia / diagnosis
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / drug therapy
  • Male
  • Neoplasm Recurrence, Local / diagnosis
  • Neoplasm Recurrence, Local / drug therapy
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use
  • Pyridines / adverse effects*
  • Pyridines / therapeutic use
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Pyridines
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • apatinib