Systematic review of colchicine neuromyopathy: Risk factors, duration and resolution

Abstract

Objective: To identify reports of colchicine-induced neuropathy and myopathy and ascertain risk factors associated with this toxicity at commonly used doses.

Methods: A systematic review of case reports was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA methodology). PubMed and EMBASE were searched through October 2021 for case reports of neuropathy and/or myopathy associated with the use of colchicine at therapeutic doses.

Results: A total of 143 cases of neuromyopathy from 99 articles were identified as having a "definite" or "probable" association with colchicine usage, as assessed by the Naranjo algorithm. Most of these cases presented with features of both neuropathy and myopathy (n=72, 51%) but symptoms of myopathy were predominant. The mean total daily dose was 1.25±0.60 mg and 48% had been taking colchicine for more than 12 months before presenting with neuromyopathy. A total of 117 (82%) of all reports had either a significant co-morbidity or possible colchicine drug-drug interaction, while 57 (40%) had both risk factors. A total of 26 cases (18%) had no significant risk factor but only 15 of these reports contained complete descriptions of the patient's co-morbidities and co-medications. Cessation of colchicine generally led to complete resolution of symptoms in 70% of cases within a median of 21 days. There were 3 deaths reported which were due to multi-organ failure despite cessation of colchicine and medical management. Colchicine was restarted at reduced doses in 15 cases and 73% had no symptom recurrence.

Conclusion: Neuromyopathy is an uncommon but reported adverse effect of colchicine. Cases generally present with proximal myopathy symptoms. Cases of colchicine neuromyopathy are largely reported in patients on commonly used doses. Renal and hepatic dysfunction and medications that inhibit cytochrome P450 3A4 isozyme (CYP3A4) and P-glycoprotein (P-gp) appear to be the most significant risk factors. Fortunately, cessation of colchicine generally leads to complete resolution of symptoms. Recommencement of colchicine at reduced doses appeared to be usually safe.

Keywords: Colchicine; Creatine kinase; Drug interactions; Liver dysfunction; Muscle; Myopathy; Nerve; Neuropathy; Renal dysfunction.