Volume 194 - Issue 11
Death and morbidity from supratherapeutic dosing of colchicine
Authors: Myles W H Smith, Darren M Roberts, Siobhann M Ritson and Richard O Day
Med J Aust 2011; 194 (11): 612-613. || doi: 10.5694/j.1326-5377.2011.tb03121.x
Published online: 6 June 2011
Published online: 6 June 2011
To the Editor: Colchicine is an alternative to anti-inflammatory agents for the treatment of acute gout.1 It is potentially toxic and can cause multiorgan dysfunction, including hepatotoxicity, neutropenia, acute kidney injury, rhabdomyolysis and hypotension. We report three cases of toxicity from supratherapeutic dosing that occurred within 2 weeks of each other. In each case, no alternative diagnoses (in particular, sepsis) were considered likely.
An 87-year-old man presented with vomiting after 3 days of profuse diarrhoea, nausea and generalised myalgia without other infective symptoms. He had been prescribed 0.5 mg colchicine daily, but he was taking 1.0 mg four times daily. Clinical features included generalised abdominal tenderness, pancytopenia, rhabdomyolysis and hepatic dysfunction. These resolved over 5 days with supportive treatment.
A 67-year-old woman presented with lethargy, diaphoresis, fever, nausea, vomiting and diarrhoea. She had been prescribed 1.0 mg colchicine initially, then 0.5 mg every 6 hours “until diarrhoea develops”. She was taking colchicine every hour despite diarrhoea. Initial clinical features included tachycardia, hypotension, tachypnoea and fever. Multiorgan dysfunction developed rapidly and despite aggressive resuscitation, including an intra-aortic balloon pump and broad-spectrum antibiotics, she died within 24 hours.
A 77-year-old woman presented with nausea, vomiting and profuse diarrhoea. She had been prescribed 1.0 mg colchicine three times daily “until diarrhoea develops”. On presentation, she was dehydrated but haemodynamically stable, with mild renal and hepatic dysfunction and creatine kinase level elevation. These resolved over 4 days with supportive treatment.
A recent randomised controlled trial demonstrated that low-dose colchicine (1.8 mg over 1 hour) was as effective as a higher dose (4.8 mg over 6 hours). Further, the adverse effects of the lower dose were similar to placebo and significantly less than those of the higher dose.2 Adapting to the Australian formulation, 1.0 mg initially and 0.5 mg 1 hour later is now recommended.3
In contrast, repeat doses of 0.5 mg until clinical improvement or side effects (in particular, diarrhoea) was previously recommended. In the cases above, the apparent dosing regimen differed significantly from current recommendations. Ineffective patient education may have also contributed to the conditions of patients 1 and 2, who up-titrated their dose. Patients 2 and 3 persisted with dosing despite gastrointestinal symptoms.
Health professionals should be aware of the new dosing recommendations. These are highlighted by the National Prescribing Service4 and the Australian medicines handbook.3 Patients with renal or hepatic impairment, or concomitant use of cytochrome P450 3A4 or P-glycoprotein inhibitors (eg, clindamycin), are at increased risk.5
References
- Rheumatology Expert Group. Therapeutic guidelines: rheumatology. Version 1. Melbourne: Therapeutic Guidelines Limited, 2006. 0_CBBDHAIG
- Terkeltaub RA, Furst DE, Bennett K, et al. High versus low dosing of oral colchicine for early acute gout flare: Twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study. Arthritis Rheum 2010; 62: 1060-1068. ref2
- Australian medicines handbook: AMH July 2010 edition. Adelaide: AMH, 2010. ref3
- National Prescribing Service. Colchicine for acute gout: updated information about dosing and drug interactions. NPS, 2010. http://www.nps.org.au/health_professionals/publications/nps_radar/2010/may_2010/brief_item_colchicine (accessed Oct 2010).
- Finkelstein Y, Aks SE, Hutson JR, et al. Colchicine poisoning: the dark side of an ancient drug. Clin Toxicol (Phila) 2010; 48: 407-414. 0_CBBHIAFB