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Published: March 2011

Colchicine: Beware of toxicity and interactions

Prescriber Update 32(1): 2
March 2011

Colchicine is approved for the treatment of acute gout when non-steroidal anti-inflammatory drugs are contraindicated or have previously been unsuccessful.

Colchicine has a low threshold for toxicity and must be used with extreme care. Colchicine is only indicated for intermittent use and patients will often initiate treatment themselves; therefore the potential exists for a severe drug interaction to occur.

Colchicine is metabolised by cytochrome P450 3A4 (CYP3A4) and excreted via the P-glycoprotein (P-gp) transport system. For patients with renal or hepatic impairment, concurrent administration of colchicine with strong CYP 3A4 inhibitors or P-gp inhibitors is contraindicated. For patients with normal renal and hepatic function a reduction in colchicine dose is recommended when concurrent treatment with a strong CYP 3A4 inhibitor or a P-gp inhibitor is required.

Strong CYP3A4 inhibitors include protease inhibitors, imidazoles and clarithromycin; moderate inhibitors include simvastatin and erythromycin.

Inhibitors of P-gp include cyclosporine, ketoconazole, protease inhibitors, and tarcolimus.

Symptoms of colchicine toxicity may be delayed by up to 12 hours, therefore all patients who are suspected of taking an overdose should be referred for immediate medical assessment. All patients should be monitored for 24 hours. Early symptoms include abdominal pain, nausea, vomiting and diarrhoea. Symptoms occurring after 1 to 7 days include: confusion, cardiac, renal and hepatic impairment, respiratory distress, hyperpyrexia and bone marrow depression.

There is no specific antidote for colchicine toxicity; charcoal may be considered, but treatment is supportive.

Key messages:

  • The lowest effective dose of colchicine should be used and must not exceed 6 mg over four days.
  • Elderly patients and patients with hepatic or renal impairment are at higher risk of colchicine toxicity.
  • Colchicine should not be used in patients with hepatic or renal impairment who are also taking CYP3A4 and P-glycoprotein inhibitors.
  • Patients need to be informed of the symptoms of overdose and encouraged to seek medical assistance if they have concerns about the amount they have taken.


The Colgout data sheet is currently being updated to provide more information on interactions: www.medsafe.govt.nz/profs/Datasheet/c/Colgouttab.pdf

References
  1. FDA (2006). Drug development and drug interactions: Table of substrates, inhibitors and inducers. Accessed 21/2/11 from: http://www.fda.gov/Drugs/DevelopmentApprovalProcess/ DevelopmentResources/DrugInteractionsLabeling/ ucm081177.htm#PgpTransport

 

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