Published: 6 March 2025
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Factors contributing to colchicine toxicity
Published: 6 March 2025
Prescriber Update 46(1): 5–7
March 2025
At their December 2024 meeting, the Medicines Adverse Reactions Committee discussed two case reports of colchicine toxicity. As a result, the Committee recommended reminding prescribers about the importance of pre-existing comorbidities and concomitant medicines when prescribing colchicine.
This article highlights factors that can increase colchicine plasma levels and lead to toxicity and describes the symptoms of colchicine toxicity.
Signs and symptoms of colchicine toxicity
Colchicine has a narrow therapeutic index and the separation between therapeutic and toxic doses is not well defined.1 Colchicine toxicity has a high mortality rate.
There is a latent period of 2 to 12 hours between colchicine overdose and the onset of gastrointestinal symptoms. The first signs of toxicity may be a feeling of burning and rawness in the mouth and throat and difficulty in swallowing, followed by severe nausea, vomiting, abdominal pain and haemorrhagic diarrhoea.2 Cardiotoxicity (increased troponin) may also develop at any time after ingestion and has a poor prognosis.
Multisystem failure generally occurs 24 to 72 hours after overdose. This generally includes central nervous system toxicity, bone marrow depression, hepatocellular and renal damage and respiratory distress. Death may occur as a result of respiratory depression, dysrhythmia, cardiovascular collapse or sepsis.2
There is no specific antidote for colchicine toxicity.2 National Poisons Centre advice is that management of acute ingestions is directed towards limiting absorption via activated charcoal and whole bowel irrigation, if possible, within 2 hours of ingestion. Beyond this, treatment is supportive. Recombinant granulocyte-stimulating factor (G-CSF) may reduce the risk of severe sepsis in cases of colchicine-induced neutropenia.3 For advice on the management of colchicine overdose, contact the National Poisons Centre on 0800 POISON (0800 764 766).
Patient comorbidities and concomitant medicines contribute to colchicine toxicity
Renal impairment2
As 10-20% of the colchicine dose is excreted in urine, renal impairment can significantly reduce the clearance and prolong the half-life of colchicine.
If the patient’s creatinine clearance is:
- ≤50 mL/min – reduce the colchicine dose by half
- ≤10 mL/min – colchicine is contraindicated.
Hepatic impairment2
Colchicine is metabolised by the liver. In patients with hepatic impairment, consider reducing the individual or total daily dose or increasing the interval between doses.
Colchicine is contraindicated in patients with severe hepatic impairment.
Elderly patients
Elderly patients are more likely to have age-related renal impairment and be taking multiple medicines that may interact with colchicine (see below).2,4 Consider alternative therapy in elderly patients who are small and slight (less than 50 kg) or who have renal or hepatic impairment.2
Drug-drug interactions
Colchicine is a substrate of the efflux transporter P-glycoprotein (P-pg) and is metabolised by cytochrome P450 3A4 (CYP 3A4). If colchicine is administered with medicines that inhibit P-gp or CYP 3A4, increased colchicine plasma concentrations are likely.2
Some medicines that can interact with colchicine include:5
- azole antifungals: itraconazole, fluconazole and ketoconazole
- macrolide antibiotics: clarithromycin, roxithromycin and erythromycin
- calcium channel blockers: diltiazem and verapamil
- amiodarone
- ciclosporin.
Colchicine is contraindicated in patients with impaired renal or hepatic function and who are taking a P-gp or strong CYP 3A4 inhibitor.2
In patients with normal renal and hepatic function who are taking a P-gp or strong CYP 3A4 inhibitor, adjust the colchicine dose as appropriate and monitor for an increase in colchicine adverse effects.5
The leukopenic and thrombocytopenic effects of colchicine may be intensified by concomitant or recent use of medicines that cause blood dyscrasias or bone marrow suppression (such as anti-inflammatory medicines, angiotensin-converting enzyme inhibitors, carbamazepine, clozapine, methotrexate, tricyclic antidepressants). Colchicine may also increase the risk of bleeding in patients taking medicines that impair blood clotting or cause haemorrhage, such as anticoagulants.2
Prescribing considerations
Check the patient’s renal and hepatic function, age and concomitant medicines when initiating and continuing colchicine treatment.
Educate patients on the symptoms of early colchicine toxicity. Advise them to stop colchicine immediately and seek medical advice if they experience gastrointestinal side effects.2,6 Postpone further treatment for at least 3 days if gastrointestinal symptoms occur.2
Counsel patients on when and how to take colchicine, as lack of understanding can be a risk factor for toxicity (eg, using for non-gout related acute pain, taking more colchicine than prescribed). Also counsel patients with small children on safe storage and disposal.7 Ingestion of any colchicine is dangerous to a toddler. Consider monthly dispensing, if appropriate.
More information
For healthcare professionals
- Refer to the colchicine data sheet
- Previous Prescriber Update articles about colchicine and the safe storage of medicines:
- Keeping patients informed about colchicine use (December 2014)
- Spotlight on colchicine (March 2018)
- Colchicine: Beware of toxicity and interactions (March 2011)
- Colchicine: painful insights from recent poisoning data in New Zealand (June 2021)
- Medicine safety reminder: avoid unintentional poisoning in the home (March 2024).
For consumers
- Consumer information leaflet on medicines for gout. Also available in te reo Māori and Samoan.
References
- Finkelstein Y, Aks SE, Hutson JR, et al. 2010. Colchicine poisoning: the dark side of an ancient drug. Clinical Toxicology 48(5): 407-14. DOI: 10.3109/15563650.2010.495348 (accessed 14 January 2025).
- Pharmacy Retailing (NZ) Limited t/a Healthcare Logistics. 2020. Colgout New Zealand Data Sheet November 2020. URL: www.medsafe.govt.nz/profs/datasheet/c/Colgouttab.pdf (accessed 26 January 2025).
- Critchley JA, Critchley LA, Yeung EA, et al. 1997. Granulocyte-colony stimulating factor in the treatment of colchicine poisoning. Human & Experimental Toxicology 16(4): 229–32. DOI: 10.1177/096032719701600413 (accessed 17 February 2025).
- Hansten PD, Tan MS, Horn JR, et al. 2023. Colchicine drug interaction errors and misunderstandings: Recommendations for improved evidence-based management. Drug Safety 46(3): 223-42. DOI: 10.1007/s40264-022-01265-1 (accessed 14 January 2025).
- New Zealand Formulary (NZF). 2024. NZF v151: Interactions Checker 1 December 2024. URL: nzf.org.nz (accessed 14 January 2025).
- New Zealand Formulary (NZF). 2024. NZF v151: Colchicine 1 December 2024. URL: nzf.org.nz/nzf_5674 (accessed 17 January 2025).
- Stamp LK, Horsley C, Te Karu L, et al. 2024. Colchicine: the good, the bad, the ugly and how to minimize the risks. Rheumatology 63(4): 936–44. DOI: https://doi.org/10.1093/rheumatology/kead625 (accessed 17 February 2025).
