Colchicine × Simvastatin

Both drugs can damage muscle on their own: simvastatin causes myopathy and rhabdomyolysis (simvastatin SmPC), and colchicine taken long term at therapeutic doses causes neuromuscular toxicity and rhabdomyolysis (colchicine SmPC). Together the risk of myopathy rises: adding one drug to a stable long-term regimen of the other has resulted in myopathy and rhabdomyolysis, including a fatal case (US colchicine label, FDA). The interaction may be pharmacokinetic, pharmacodynamic or both (US colchicine label). Such cases with this combination have also been reported in patients with renal impairment (simvastatin SmPC).

Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Severe cases progress to rhabdomyolysis with acute kidney injury. The risk is higher in older patients and in renal impairment.

Before combining, weigh the benefit against the increased risk of myopathy and rhabdomyolysis (US simvastatin and colchicine labels, FDA). If it is used, monitor for muscle pain, tenderness and weakness, especially at the start of treatment and when the dose of either drug is increased (US simvastatin label); creatine kinase monitoring will not necessarily prevent severe myopathy (US colchicine label). Monitor patients with renal impairment closely (simvastatin SmPC). Adjust the colchicine dose to age and renal function: in older patients and in renal impairment the total dose over a 4-day gout attack should not exceed 3 mg, in moderate renal impairment the dose may need to be halved, and in severe renal impairment colchicine is contraindicated (colchicine SmPC). If muscle toxicity appears, interrupt or stop colchicine (US colchicine label); symptoms usually resolve within one week to several months after stopping (colchicine SmPC).