simvastatin and amiodarone

Amiodarone inhibits CYP3A4, the enzyme responsible for simvastatin metabolism. This increases simvastatin plasma concentrations, leading to a higher risk of dose-dependent skeletal muscle toxicity.

Co-administration increases the risk of myopathy and rhabdomyolysis, which can manifest as muscle pain, weakness, and dark urine. Rhabdomyolysis may lead to acute kidney injury and be life-threatening.

Avoid concomitant use if possible. If combination is necessary, limit simvastatin dose to no more than 20 mg daily and monitor patients for signs of myopathy, including creatine kinase levels. Consider alternative statins less dependent on CYP3A4, such as pravastatin or rosuvastatin.

This interaction is well established in prescribing information and multiple case reports. Clinical guidelines recommend dose restrictions and monitoring.