Drugs That Interact With Colchicine Via Inhibition of Cytochrome P450 3A4 and P-Glycoprotein: A Signal Detection Analysis Using a Database of Spontaneously Reported Adverse Events (FAERS)

Ann Pharmacother. 2023 Oct;57(10):1137-1146. doi: 10.1177/10600280221148031. Epub 2023 Jan 23.


Background: Colchicine has a narrow therapeutic index. Its toxicity can be increased due to concomitant exposure to drugs inhibiting its metabolic pathway; these are cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp).

Objective: To examine clinical outcomes associated with colchicine drug interactions using the spontaneous reports of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).

Methods: We conducted a disproportionality analysis using FAERS data from January 2004 through June 2020. The reporting odds ratio (ROR) and observed-to-expected ratio (O/E) with shrinkage for adverse events related to colchicine's toxicity (ie, rhabdomyolysis/myopathy, agranulocytosis, hemorrhage, acute renal failure, hepatic failure, arrhythmias, torsade de pointes/QT prolongation, and cardiac failure) were compared between FAERS reports.

Results: A total of 787 reports included the combined mention of colchicine, an inhibitor of both CYP3A4 and P-gp drug, and an adverse event of interest. Among reports that indicated the severity, 61% mentioned hospitalization and 24% death. A total of 37 ROR and 34 O/E safety signals involving colchicine and a CYP3A4/P-gp inhibitor were identified. The strongest ROR signal was for colchicine + atazanavir and rhabdomyolysis/myopathy (ROR = 35.4, 95% CI: 12.8-97.6), and the strongest O/E signal was for colchicine + atazanavir and agranulocytosis (O/E = 3.79, 95% credibility interval: 3.44-4.03).

Conclusion and relevance: This study identifies numerous safety signals for colchicine and CYP3A4/P-gp inhibitor drugs. Avoiding the interaction or monitoring for toxicity in patients when co-prescribing colchicine and these agents is highly recommended.

Keywords: colchicine; cytochrome P450 CYP3A inhibitors; drug interactions; drug-related side effects and adverse reactions; pharmacovigilance.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Adverse Drug Reaction Reporting Systems
  • Atazanavir Sulfate
  • Colchicine* / adverse effects
  • Cytochrome P-450 CYP3A* / metabolism
  • Humans
  • Pharmaceutical Preparations
  • Signal Detection, Psychological
  • United States
  • United States Food and Drug Administration


  • Pharmaceutical Preparations
  • Colchicine
  • Cytochrome P-450 CYP3A
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Atazanavir Sulfate
  • ATP Binding Cassette Transporter, Subfamily B