Colchicine × Simvastatin

Simvastatin is metabolised by CYP3A4; colchicine uses the same route and inhibits it. Simvastatin plasma levels rise, amplifying additive myotoxicity.

Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Severe cases progress to rhabdomyolysis with acute kidney injury. Symptoms appear within 1–4 weeks of co-administration.

Avoid prolonged combination. For acute gout, a short colchicine course (3–5 days) at 0.3 mg every other day is acceptable with muscle symptom and creatine kinase monitoring. For long-term gout prophylaxis, switch to pravastatin (no CYP3A4 dependence) or replace colchicine with allopurinol.