Rhabdomyolysis secondary to a drug interaction between simvastatin and clarithromycin

OBJECTIVE: TO report a case of rhabdomyolysis resulting from concomitant us e of clarithromycin and simvastatin. CASE SUMMARY: A 64-year-old African-American man was admitted to the hospit al for worsening renal failure, elevated creatine phosphokinase, diffuse mu scle pain, and severe muscle weakness. About three weeks prior to admission , the patient was started on clarithromycin for sinusitis. The patient had been receiving simvastatin for approximately six months. He was treated agg ressively with intravenous hydration, sodium bicarbonate, and hemodialysis. A muscle biopsy revealed necrotizing myopathy secondary to a toxin. The pa tient continued to receive intermittent hemodialysis until his death from i nfectious complications that occurred three months after admission. There w ere several factors that could have increased his risk for developing rhabd omyolysis, including chronic renal failure. DISCUSSION: Clarithromycin is a potent inhibitor of CYP3A4, the major enzym e responsible for simvastatin metabolism. The concomitant administration of macrolide antibiotics and other hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have resulted in previous reports of rhabdomyolysis. Other factors may increase the risk of this drug interaction, including the administration of other medications that are associated with myopathy, und erlying renal insufficiency, and administration of high doses of HMG-CoA re ductase inhibitors. CONCLUSIONS: Macrolide antibiotics inhibit the metabolism of HMG-CoA reduct ase inhibitors that are metabolized by CYP3A4 (i.e., atorvastatin, cerivast atin, lovastatin, simvastatin). This interaction may result in myopathy and rhabdomyolysis, particularly in patients with renal insufficiency or those who are concurrently taking medications associated with myopathy.