CYP3A4/P-glycoprotein inhibitors related colchicine toxicity mimicking septic shock

BMJ Case Rep. 2023 Oct 9;16(10):e257186. doi: 10.1136/bcr-2023-257186.

Abstract

Colchicine toxicity is uncommon when patients receive a therapeutic dose regularly. However, inadvertent drug interactions can result in unpredicted adverse outcomes. The toxicity of colchicine can manifest in various ways, ranging from mild and non-specific symptoms to severe form known as multiple organ dysfunction syndrome. This case highlights (1) the diagnostic challenge that arises when distinguishing between the severe manifestation of colchicine toxicity and septic shock and (2) concomitant prescription of colchicine with potent CYP3A4 and P-glycoprotein inhibitors (ie, clarithromycin) can lead to colchicine toxicity despite normal renal and hepatic clearance. Unfortunately, specific tests of colchicine toxicity were not routinely available. A high index of clinical suspicion and recognition of drug interactions with their common presentations are crucial for making diagnosis and management. Failure to recognise drug toxicity can result in poor outcomes.

Keywords: Adult intensive care; Drug interactions; Toxicology.

Publication types

  • Case Reports

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • Colchicine* / toxicity
  • Cytochrome P-450 CYP3A / metabolism
  • Cytochrome P-450 CYP3A Inhibitors
  • Drug Interactions
  • Glycoproteins
  • Humans
  • Shock, Septic* / drug therapy

Substances

  • ATP Binding Cassette Transporter, Subfamily B
  • Colchicine
  • CYP3A4 protein, human
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 CYP3A Inhibitors
  • Glycoproteins