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Related Experiment Videos

Acute colchicine intoxication during clarithromycin administration.

Florence Rollot1, Olivier Pajot, Laurence Chauvelot-Moachon

  • 1Internal Medicine, Cochin Hospital, Paris, France.

The Annals of Pharmacotherapy
|October 21, 2004
PubMed
Summary

Combining colchicine with clarithromycin can lead to dangerous colchicine intoxication. This drug interaction, particularly in elderly patients, necessitates careful monitoring and dose adjustment to prevent toxicity.

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Area of Science:

  • Pharmacology
  • Toxicology
  • Internal Medicine

Background:

  • Colchicine is a key treatment for familial Mediterranean fever (FMF), microcrystalline arthritis, and Behcet's disease.
  • Colchicine is primarily eliminated via biliary excretion, with lesser roles for renal elimination and CYP450 metabolism.
  • Colchicine is a substrate of P-glycoprotein, a transporter crucial for drug efflux.

Observation:

  • A 76-year-old FMF patient on chronic colchicine developed severe toxicity (fever, diarrhea, pancytopenia, acidosis) after a 7-day course of clarithromycin, amoxicillin, and omeprazole.
  • Symptoms emerged three days into the clarithromycin regimen, resolving upon colchicine dose reduction and rehydration.
  • Alopecia, a known side effect of colchicine toxicity, appeared two weeks post-treatment.

Findings:

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  • The coadministration of colchicine and clarithromycin, a macrolide antibiotic, resulted in probable colchicine intoxication.
  • Macrolides like clarithromycin are known inhibitors of P-glycoprotein and CYP450 enzymes, potentially impairing colchicine's biliary excretion.
  • This drug interaction highlights the risk of reduced drug elimination and subsequent toxicity.

Implications:

  • Elderly patients and those with renal impairment are at higher risk for colchicine toxicity when co-administered with P-glycoprotein inhibitors.
  • Extreme caution is advised when prescribing colchicine concurrently with macrolide antibiotics or other P-glycoprotein inhibitors.
  • This case underscores the importance of pharmacovigilance for drug-drug interactions, especially in vulnerable patient populations.