In the continued fight against COVID-19, a January 22, 2021 press release from the Montreal Heart Institute touted the potential of colchicine, citing results from the COLCORONA trial [1, 2]. We’ve learned to be especially skeptical of any study results reported only via press release before undergoing full peer-review and publication. Nevertheless, the authors claim a non-significant (p=0.08) relative risk reduction of 19% (absolute risk reduction 1.1%) in hospitalizations, mechanical ventilation, and death. Note that the pre-print of the study has still not been peer-reviewed [3]. This study comes on the heels of the much smaller GRECCO-19 study published in June 2020 [4].

Early in 2020, promising results on hydroxychloroquine for treatment of COVID-19 led to a large increase in its use in outpatients and inpatients. It is now known that there is virtually no role for hydroxychloroquine and that this spike in use led to serious toxicity both from therapeutic use and overdose [5, 6]. The same may be anticipated for colchicine. And, if there is a drug that toxicologists fear more than hydroxychloroquine in overdose, it’s colchicine.

5 things to know about colchicine toxicity

1. Colchicine inhibits microtubule formation and function, thereby inhibiting mitosis.

  • It also is a GABA-A antagonist.

2. Acute toxicity occurs in 3 phases.

  • 0-24 hours: Nausea, vomiting, diarrhea, salt and water depletion, and  leukocytosis
  • 1-7 days: Sudden cardiac death (24-48 hours), pancytopenia, acute kidney injury, sepsis, acute respiratory distress syndrome, rhabdomyolysis, and electrolyte imbalance
  • >7 days: Alopecia, myopathy, neuropathy, and myoneuropathy

3. Colchicine levels are not helpful.

  • They also aren’t readily available at most institutions.

4. Hemodialysis doesn’t remove the toxin.

  • Colchicine’s volume of distribution is large.
  • Extracorporeal treatment can be employed if kidney toxicity results from the poisoning.

5. There is no antidote.

  • Management is largely supportive with IV fluids, vasopressors, and colony-stimulating factors.
  • Experimental anti-colchicine Fab fragments are being studied [7].

This 2010 Clinical Toxicology review article provides further information and education on colchicine toxicity.

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References:

  1. Montreal Heart Institute. Colchicine reduces the risk of COVID-19-related complications. GlobalNewswire website. January 22, 2021. Accessed January 26, 2021.
  2. Montretal Heart Institute. ColCorona. Accessed January 26, 2021.
  3. Tardif J-C, Bouabdallaoui N, L’Allier PL, et al. Efficacy of colchicine in non-hospitalized patients with covid-19. medRxiv. doi: Epub 2021 Jan 27.
  4. Deftereos SG, Giannopoulos G, Vrachatis DA, et al. Effect of colchicine vs standard care on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019: the grecco-19 randomized clinical trial. JAMA Netw Open.  2020;3(6):e2013136. doi: 10.1001/jamanetworkopen.2020.13136. PMID: 32579195.
  5. Mahan KM, Hayes BD, North CM, et al. Utility of hypertonic saline and diazepam in covid-19–related hydroxychloroquine toxicity. The Journal of Emergency Medicine. doi: 10.1016/j.jemermed.2020.10.048. Epub 2020 Oct 2020. PMID: 33353811.
  6. Chai PR, Ferro EG, Kirshenbaum JM, et al. Intentional hydroxychloroquine overdose treated with high-dose diazepam: an increasing concern in the covid-19 pandemic. J Med Toxicol. 2020;16(3):314-320. doi: 10.1007/s13181-020-00790-8. PMID: 32514696.
  7. Eddleston M, Fabresse N, Thompson A, et al. Anti-colchicine Fab fragments prevent lethal colchicine toxicity in a porcine model: a pharmacokinetic and clinical study. Clinical Toxicology. 2018;56(8):773-781. doi: 10.1080/15563650.2017.1422510. PMID: 29334816.

 

Bryan D. Hayes, PharmD, DABAT, FAACT, FASHP

Bryan D. Hayes, PharmD, DABAT, FAACT, FASHP

Leadership Team, ALiEM
Creator and Lead Editor, Capsules series, ALiEMU
Attending Pharmacist, EM and Toxicology, MGH
Assistant Professor of EM, Harvard Medical School
Bryan D. Hayes, PharmD, DABAT, FAACT, FASHP

@PharmERToxGuy

EM Pharmacist & Toxicologist @MassGeneralEM | Asst Prof @HarvardMed/@EMRES_MGHBWH | @ALiEMteam leadership | Capsules creator, ALiEMU | President, ABAT | #FOAMed