What medications should not be taken with colchicine?

Medications to Avoid with Colchicine

Colchicine should not be taken with strong P-glycoprotein and/or CYP3A4 inhibitors such as cyclosporin, clarithromycin, ketoconazole, ritonavir, and certain other medications due to risk of potentially fatal toxicity. 1, 2

Strong CYP3A4/P-glycoprotein Inhibitors (Contraindicated or Requiring Significant Dose Reduction)

• Macrolide antibiotics: Clarithromycin, erythromycin (clarithromycin has been associated with life-threatening colchicine toxicity) 1, 3
• Antifungals: Ketoconazole, itraconazole, posaconazole, voriconazole 2
• Immunosuppressants: Cyclosporine (fatal colchicine toxicity has been reported) 2, 4
• HIV protease inhibitors: Ritonavir, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, saquinavir, tipranavir 2
• Other strong inhibitors: Ranolazine 2

Moderate CYP3A4 Inhibitors (Require Dose Adjustment)

• Calcium channel blockers: Verapamil, diltiazem (neuromuscular toxicity has been reported) 2
• Other moderate inhibitors: Aprepitant, fluconazole, fosamprenavir, amprenavir 2
• Food: Grapefruit juice 2

Medications That Increase Risk of Myotoxicity

• Statins: Particularly simvastatin and atorvastatin (increased risk of myopathy and rhabdomyolysis) 1, 4
• Other lipid-lowering drugs: Fibrates (increased risk of myopathy) 4

Medications That Affect Renal Function

• Nephrotoxic drugs: Any medication that can impair renal function increases colchicine toxicity risk 4
• Tyrosine kinase inhibitors: Sunitinib (case report of severe toxicity) 5

Special Considerations

• Severe renal impairment: Colchicine should be avoided in patients with severe renal impairment (GFR <30 mL/min) who are also taking P-glycoprotein inhibitors 1, 6
• Hepatic impairment: Patients with hepatic dysfunction should avoid colchicine with P-glycoprotein inhibitors 2, 7

Clinical Manifestations of Dangerous Interactions

• Early signs: Diarrhea (earliest warning sign), nausea, vomiting 4
• Serious toxicity: Pancytopenia, bone marrow failure, multiorgan failure, cardiac arrhythmias 3, 7
• Neuromuscular effects: Myopathy, rhabdomyolysis 1, 4

Monitoring Recommendations

• Monitor for early signs of toxicity, especially diarrhea 4
• In patients on statins, monitor for muscle-related signs and symptoms 1
• Monitor liver enzymes regularly; reduce colchicine if liver enzymes exceed twice the upper limit of normal 1
• In patients with decreased renal function, monitor creatine phosphokinase (CPK) and reduce colchicine dose accordingly 1

Dose Adjustment Recommendations

• For patients on strong CYP3A4/P-gp inhibitors: Reduce colchicine to 0.3 mg once daily or 0.3 mg once every other day depending on the specific medication 2
• For patients on moderate CYP3A4 inhibitors: Reduce colchicine to 0.3 mg twice daily or 0.6 mg once daily 2
• For acute gout flares in patients on interacting medications: Use alternative treatments (NSAIDs, corticosteroids) 1

Remember that colchicine has a narrow therapeutic window, and interactions can rapidly lead to potentially fatal toxicity. When in doubt, choose an alternative treatment for gout flares or consider dose reduction based on the specific interacting medication.