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Severe rhabdomyolysis secondary to simvastatin and acenocoumarol
European Journal of Internal Medicine 18 (2007) 165 www.elsevier.com/locate/ejim
Letter to the Editor
Severe rhabdomyolysis secondary to simvastatin and acenocoumarol A. Salinas ⁎, J. Solís, L.A. Rico Service of Internal Medicine, Fundación Jiménez Díaz-Clínica de la Concepción, Universidad Autónoma de Madrid. Madrid, Spain Received 9 July 2006; accepted 14 July 2006
Keywords: Rhabdomyolysis; Simvastatin; Acenocoumarol; Creatine kinase; Anticoagulant
A 69-year-old man was admitted to our hospital due to muscular pain in his legs. He had a history of hypertension, diabetes mellitus, and hypercholesterolemia. In 1991, he had received a heart allotransplant in our hospital due to advanced ischemic heart disease and he had been taking immunosuppressive drugs ever since. In 2004, the patient was diagnosed as having non-Hodgkin's lymphoma and was treated with chemotherapy, after which he remained free of disease. He also had peripheral vascular disease. Three weeks before admission, the patient was found to have a lung thromboembolism, and therapy with acenocoumarol was initiated. His complete list of medications now included diltiazem, repaglinide, simvastatin, cyclosporin, azathioprine, pentoxifylline, pantoprazole, and acenocoumarol. Two days before admission, the patient started feeling weakness and intense pain in his thighs, which interfered with his walking. The patient denied experiencing trauma, doing any strenuous exercise, having a fever, or having a history of substance abuse. He had never before suffered similar symptoms. The only new drug he was taking was acenocoumarol; the others he had been taking for a long time with no change in the dosage. His physical examination was normal and, on neurological examination, weakness and pain in the legs was noted. Strength was 4/5 in both quadriceps muscles. The deep tendon reflexes were ++/+++ bilaterally and the plantar responses were flexor. Sensation was normal. Laboratory studies revealed a white blood cell count of 13,640/mm3, a platelet count of 215,000/mm3, and a hematocrit of 45%. Glucose was 215 mg/dl, creatinine 2.24 mg/dl, sodium 132 mmol/l, potassium 3.88 mmol/l, and creatine kinase 29,674 U/l. Intravenous fluids were administered, and simvastatin and acenocoumarol were stopped. The patient's health status
improved and muscular pain disappeared. After 9 days in the hospital, creatinine was 1.38 mg/dl and creatine kinase 668 U/ l and the patient was asymptomatic. Simvastatin is widely used in the treatment of hypercholesterolemia. Myalgias are a recognized side effect. Rhabdomyolysis, with an increase in creatine kinase blood levels, is relatively infrequent when used alone, but its incidence rises when used concomitantly with other drugs [1]. Although rhabdomyolysis secondary to the administration of simvastatin and warfarin has been reported [2], we are not aware of any case of severe rhabdomyolyisis caused by simvastatin and acenocoumarol. Our patient had been taking the same dose of simvastatin for years; the only new drug he had was acenocoumarol, which he had taken for only 3 weeks. The initial clinical course and later outcome favor an interaction of these two drugs, leading to acute renal failure and severe muscular damage. Unlike in the United States, where the most common anticoagulant is warfarin, in Europe acenocoumarol is the most common one. We consider severe rhabdomyolysis to be an important side effect since so many patients are being treated with simvastatin and acenocoumarol. The lack of previous reports is rather surprising, though it may, in part, be due to careful monitoring of INR in patients and subsequent reductions in the acenocoumarol doses [2]. References [1] Omar MA, Wilson JP. FDA adverse event reports on statin-associated rhabdomyolysis. Ann Pharmacother Feb 2002;36(2):288–95. [2] Mogyorósi A, Bradley B, Showalter A, Schubert ML. Rhabdomyolysis and acute renal failure due to combination therapy with simvastatin and warfarin. J Intern Med 1999;246:599–602.
⁎ Corresponding author. E-mail address: [email protected] (A. Salinas). 0953-6205/$ - see front matter © 2006 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.ejim.2006.07.030
Letter to the Editor
Severe rhabdomyolysis secondary to simvastatin and acenocoumarol A. Salinas ⁎, J. Solís, L.A. Rico Service of Internal Medicine, Fundación Jiménez Díaz-Clínica de la Concepción, Universidad Autónoma de Madrid. Madrid, Spain Received 9 July 2006; accepted 14 July 2006
Keywords: Rhabdomyolysis; Simvastatin; Acenocoumarol; Creatine kinase; Anticoagulant
A 69-year-old man was admitted to our hospital due to muscular pain in his legs. He had a history of hypertension, diabetes mellitus, and hypercholesterolemia. In 1991, he had received a heart allotransplant in our hospital due to advanced ischemic heart disease and he had been taking immunosuppressive drugs ever since. In 2004, the patient was diagnosed as having non-Hodgkin's lymphoma and was treated with chemotherapy, after which he remained free of disease. He also had peripheral vascular disease. Three weeks before admission, the patient was found to have a lung thromboembolism, and therapy with acenocoumarol was initiated. His complete list of medications now included diltiazem, repaglinide, simvastatin, cyclosporin, azathioprine, pentoxifylline, pantoprazole, and acenocoumarol. Two days before admission, the patient started feeling weakness and intense pain in his thighs, which interfered with his walking. The patient denied experiencing trauma, doing any strenuous exercise, having a fever, or having a history of substance abuse. He had never before suffered similar symptoms. The only new drug he was taking was acenocoumarol; the others he had been taking for a long time with no change in the dosage. His physical examination was normal and, on neurological examination, weakness and pain in the legs was noted. Strength was 4/5 in both quadriceps muscles. The deep tendon reflexes were ++/+++ bilaterally and the plantar responses were flexor. Sensation was normal. Laboratory studies revealed a white blood cell count of 13,640/mm3, a platelet count of 215,000/mm3, and a hematocrit of 45%. Glucose was 215 mg/dl, creatinine 2.24 mg/dl, sodium 132 mmol/l, potassium 3.88 mmol/l, and creatine kinase 29,674 U/l. Intravenous fluids were administered, and simvastatin and acenocoumarol were stopped. The patient's health status
improved and muscular pain disappeared. After 9 days in the hospital, creatinine was 1.38 mg/dl and creatine kinase 668 U/ l and the patient was asymptomatic. Simvastatin is widely used in the treatment of hypercholesterolemia. Myalgias are a recognized side effect. Rhabdomyolysis, with an increase in creatine kinase blood levels, is relatively infrequent when used alone, but its incidence rises when used concomitantly with other drugs [1]. Although rhabdomyolysis secondary to the administration of simvastatin and warfarin has been reported [2], we are not aware of any case of severe rhabdomyolyisis caused by simvastatin and acenocoumarol. Our patient had been taking the same dose of simvastatin for years; the only new drug he had was acenocoumarol, which he had taken for only 3 weeks. The initial clinical course and later outcome favor an interaction of these two drugs, leading to acute renal failure and severe muscular damage. Unlike in the United States, where the most common anticoagulant is warfarin, in Europe acenocoumarol is the most common one. We consider severe rhabdomyolysis to be an important side effect since so many patients are being treated with simvastatin and acenocoumarol. The lack of previous reports is rather surprising, though it may, in part, be due to careful monitoring of INR in patients and subsequent reductions in the acenocoumarol doses [2]. References [1] Omar MA, Wilson JP. FDA adverse event reports on statin-associated rhabdomyolysis. Ann Pharmacother Feb 2002;36(2):288–95. [2] Mogyorósi A, Bradley B, Showalter A, Schubert ML. Rhabdomyolysis and acute renal failure due to combination therapy with simvastatin and warfarin. J Intern Med 1999;246:599–602.
⁎ Corresponding author. E-mail address: [email protected] (A. Salinas). 0953-6205/$ - see front matter © 2006 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.ejim.2006.07.030