Key result
Colchicine at 0.33 mg/kg linked to fatal multiple organ failure driven by severe drug-drug interactions.
Case Report (n=1)
Coingestion of CYP3A4 and P-glycoprotein inhibitors like atorvastatin can lead to fatal multiple organ failure even in relatively low-dose colchicine overdoses.
Alerts to heightened colchicine toxicity risk with CYP3A4/P-gp inhibitors even at low doses; leaves open formal risk quantification in larger cohorts.
INTRODUCTION: Although the ingestion of a dose of colchicine lower than 0.5 mg/kg is usually complicated by a mortality rate less than 5%, severe complications may be associated with drug-drug interactions in case of overdose combining other drugs. CASE REPORT: A 33-year-old previously healthy woman was admitted after a drug overdose combining colchicine, atorvastatin, ibuprofen, diclofenac, and furosemide. The amount of colchicine ingested was exactly 20 mg, corresponding to 0.33 mg/kg. Despite this relatively low dose, she presented the clinical course that is usually seen with much larger colchicine ingestions. She developed acute renal and liver failure, acute lung injury, pancytopenia with sepsis, rhabdomyolysis, hypertriglyceridemia, and ultimately died on Day 14 from hyperammonemic encephalopathy, refractory hypoxemia, and cardiac arrhythmias. DISCUSSION: Serious drug-drug interactions may have complicated colchicine poisoning. In particular, atorvastatin, an inhibitor of P-glycoprotein and cytochrome P450 3A4, was likely responsible for an increased severity of rhabdomyolysis. In addition, propofol used for sedation during mechanical ventilation may have induced symptoms consistent with "propofol infusion syndrome," with further muscular injury and hypertriglyceridemia. The mechanism of death was unusual and similar to Reye's syndrome.
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Montiel et al. (2010) conducted a case report in Colchicine overdose (n=1). Colchicine overdose with coingestants was evaluated on Clinical course and mortality. A relatively low dose of colchicine (0.33 mg/kg) combined with other drugs resulted in fatal multiple organ failure on day 14, likely exacerbated by severe drug-drug interactions.
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