What is the lowest lethal dose of colchicine?

Abstract

Colchicine is known for its narrow therapeutic index, unclear boundaries between non-toxic, toxic and lethal doses and limited use due to its toxicity. In the scientific literature the opinion has prevailed that ‘The lowest reported lethal doses of oral colchicine have ranged from 7 to 26 mg’. In conjunction with our results of a life-saving effect of higher loading doses of colchicine up to 5 mg for the Coronavirus disease 2019 (COVID-19) treatment, we analyze the deaths reported in the literature with colchicine doses of 7–7.5 mg and show that they are due to drug interactions. To a large extent, this also applies to the described lethal doses of colchicine of 15–18 mg. We consider that doses of colchicine below 0.1 mg/kg are completely safe, and those between 0.1 and 0.2 mg/kg may lead to intoxication in some cases, but not to death. Hence, we suggest that the classic statement quoted above needs to be reworded as follows: ‘The lowest reported lethal doses of oral colchicine have ranged from 15 to 26 mg’. Our analysis indicates that colchicine can be used safely to treat COVID-19 in the mentioned doses, provided that liver and kidney damage are not present and adverse drug interactions are avoided.