From the Guidelines
Colchicine should be used with caution in patients with impaired renal function due to increased risk of toxicity, and the dose should be reduced in patients with renal impairment, as recommended by the 2016 updated EULAR evidence-based recommendations for the management of gout 1.
Key Considerations
- For patients with mild to moderate renal impairment (GFR 30-80 mL/min), dose reduction is recommended - typically 50% of the standard dose.
- In severe renal impairment (GFR <30 mL/min), colchicine should generally be avoided or used at significantly reduced doses with careful monitoring.
- Standard dosing in patients with normal renal function is typically 0.6 mg once or twice daily for chronic conditions or 1.2 mg followed by 0.6 mg one hour later for acute gout flares.
Rationale
The reason for this caution is that colchicine is partially eliminated by the kidneys, and reduced renal clearance leads to drug accumulation and increased risk of serious adverse effects including neuromuscular toxicity, gastrointestinal symptoms, bone marrow suppression, and in severe cases, multi-organ failure, as noted in the study by Richette P, et al. 1.
Monitoring and Alternatives
Close monitoring for signs of toxicity is essential, including gastrointestinal symptoms (nausea, vomiting, diarrhea), muscle weakness, and abnormal blood counts. Alternative medications like NSAIDs (if not contraindicated) or corticosteroids may be safer options for conditions like gout in patients with significant kidney dysfunction, as suggested by the European Society of Cardiology working group on cardiovascular pharmacotherapy 1.
Additional Guidance
A pharmacokinetic study showed that strong P-glycoprotein and/or CYP3A4 inhibitors such as cyclosporin, clarithromycin, verapamil and ketoconazole when prescribed with colchicine increased colchicine plasma concentration, thereby exposing patients to risk of serious side effects, as reported in the Annals of the Rheumatic Diseases 1.
From the FDA Drug Label
Colchicine dosing must be individualized according to the patient's renal function [see Use in Specific Populations (8.6)] For prophylaxis of gout flares in patients with mild (estimated creatinine clearance [Cl cr] 50 to 80 mL/min) to moderate (Cl cr 30 to 50 mL/min) renal function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine. However, in patients with severe impairment, the starting dose should be 0.3 mg/day and any increase in dose should be done with close monitoring.
Colchicine is not absolutely safe for patients with impaired kidney function. The dose of colchicine should be adjusted based on the patient's renal function.
- For patients with mild to moderate renal impairment, the dose does not need to be adjusted, but close monitoring for adverse effects is recommended.
- For patients with severe renal impairment, the starting dose should be reduced to 0.3 mg/day, and any increase in dose should be done with close monitoring.
- For patients undergoing dialysis, the starting dose for prophylaxis of gout flares should be 0.3 mg given twice a week, and the total recommended dose for treatment of gout flares should be reduced to a single dose of 0.6 mg (one tablet), with a treatment course not repeated more than once every two weeks 2.
From the Research
Safety of Colchicine in Impaired Kidney Function
- Colchicine is a medication used to treat gout and familial Mediterranean fever, but its use in patients with impaired kidney function is limited due to the risk of toxicity 3, 4, 5, 6, 7.
- Patients with impaired kidney function are at increased risk of developing colchicine toxicity, which can manifest as neuromyopathy, myopathy, and other adverse effects 4, 6.
- The risk of colchicine toxicity is higher in patients with moderate to severe renal impairment, and dose adjustments may be necessary to minimize this risk 3, 5.
- Studies have shown that reduced doses of colchicine, such as 0.3-0.5 mg/day, may be effective and well-tolerated in patients with severe chronic kidney disease 5.
- However, colchicine should be used with caution in patients with kidney impairment, and careful monitoring of adverse effects is necessary 3, 4, 6, 7.
Dosing Considerations
- Patients with mild renal impairment (eGFR 60-89 mL/min/1.73 m2) may not require dose adjustments, but those with moderate to severe renal impairment may need reduced doses 3.
- The use of colchicine oral solution may allow for more precise dosing and reduced risk of toxicity in patients with renal impairment 3.
- Concomitant use of other medications, such as simvastatin or cyclosporine, may increase the risk of colchicine toxicity in patients with renal impairment 4.
Adverse Effects
- Colchicine toxicity can manifest as neuromyopathy, myopathy, and other adverse effects, including diarrhea, acute kidney injury, and muscle weakness 4, 6.
- Acute pancreatitis has been reported as a rare adverse effect of colchicine, even with therapeutic dosing, in patients with pre-existing renal impairment 7.
- Elevated creatine kinase (CK) levels and abnormal electromyography findings may be indicative of colchicine-induced myopathy 6.