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Evidence of Clinically Meaningful Drug–Drug Interaction With Concomitant Use of Colchicine and Clarithromycin

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Abstract

Introduction

Colchicine is currently approved for the treatment of gout and familial Mediterranean fever, among other conditions. Clarithromycin, a strong inhibitor of CYP3A4 and P-glycoprotein, dramatically increases colchicine’s half-life, augmenting the risk of a life-threatening adverse reaction when used inadvertently with colchicine.

Objectives

The aim of this study was to examine the evidence and clinical implications of concomitant use of colchicine and clarithromycin.

Methods

Case reports of colchicine–clarithromycin co-administration were searched using the FDA’s Adverse Event Reporting System (FAERS) database. PubMed, EMBASE, and Web of Science electronic databases were also searched from January 2005 through November 2019 for articles reporting colchicine–clarithromycin concomitant use. Individual reports were reviewed to identify consequences of coadministration, dose, days to onset of interaction, symptoms, evidence of renal disease, time to resolution of symptoms, and Drug Interaction Probability Scale (DIPS) rating.

Results

The FAERS search identified 58 reported cases, nearly 53% of which were from patients aged between 65 and 85 years. Of 30 reported deaths, 11 occurred in males, and 19 in females. Other frequent complications reported in FAERS included diarrhea (31%), pancytopenia (22%), bone marrow failure (14%), and vomiting (14%). From published literature, we identified 20 case reports of concomitant exposure, 19 of which were rated ‘probable’ and one ‘possible’ according to DIPS rating. Of these cases, four ‘probable’ patients expired. The documented onset of colchicine toxicity occurred within 5 days of starting clarithromycin, and death within 2 weeks of concomitant exposure.

Conclusion

Clinical manifestations of colchicine–clarithromycin interaction may resemble other systemic diseases and may be life threatening. Understanding this clinically meaningful interaction can help clinicians avoid unsafe medication combinations.

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Author information

Authors and Affiliations

  1. Skaggs School of Pharmacy and Pharmaceutical Sciences, Center for Pharmaceutical Outcomes Research, University of Colorado, Aurora, CO, USA

    Lorenzo Villa Zapata

  2. School of Pharmacy, University of Washington, Seattle, WA, USA

    Philip D. Hansten

  3. Department of Pharmacy Practice, School of Pharmacy and Associate Director, Pharmacy Services UW Medicine, University of Washington, Seattle, WA, USA

    John R. Horn

  4. Department of Biomedical Informatics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    Richard D. Boyce

  5. Community and Health Systems Science, College of Nursing, The University of Arizona, Tucson, AZ, USA

    Sheila Gephart

  6. Department of Biomedical Engineering and Department of Systems and Industrial Engineering, College of Engineering, The University of Arizona, Tucson, AZ, USA

    Vignesh Subbian

  7. Department of Pharmacy, Banner University Medical Center, Tucson, AZ, USA

    Andrew Romero

  8. Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, Utah, USA

    Daniel C. Malone

Authors
  1. Lorenzo Villa Zapata
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Corresponding author

Correspondence to Daniel C. Malone.

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Funding

This project was supported by grant R01HS025984 from the Agency for Healthcare Research and Quality. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality.

Conflict of interest

All authors have completed the ADIS uniform disclosure. There was no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years, and no other relationships or activities that could appear to have influenced the submitted work.

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None.

Data availability

Reports of colchicine–clarithromycin drug interactions in FAERS can be publicly accessed via: https://www.fda.gov/drugs/questions-and-answers-fdas-adverse-event-reporting-system-faers/fda-adverse-event-reporting-system-faers-public-dashboard

Disclaimer

The authors affirm that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

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Villa Zapata, L., Hansten, P.D., Horn, J.R. et al. Evidence of Clinically Meaningful Drug–Drug Interaction With Concomitant Use of Colchicine and Clarithromycin. Drug Saf 43, 661–668 (2020). https://doi.org/10.1007/s40264-020-00930-7

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  • DOI: https://doi.org/10.1007/s40264-020-00930-7

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