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International Journal of Medicine and Medical Sciences ISSN: 2167-0447 Vol. 2 (12), pp. 269-270, December, 2012.
Available online at www.internationalscholarsjournals.org International Scholars Journals

Case Report Rosuvastatin induced rhabdomyolysis – Rare case
reported in Batticaloa
Pirasath S.1*, Jasotharan V.2, Sundaresan K. T.3
1 Post Intern Medical Officer, Teaching Hospital, Batticaloa. 2Medical student, Faculty of Health Care Sciences, Eastern University of Sri Lanka. 3Consultant Physician, Teaching Hospital, Batticaloa Received 09 July, 2012; Accepted 12 December, 2012 We reported a case of rosuvastatin induced rhabdomyolysis in a patient, who presented with one week
history of bilateral thigh, back and shoulder pain and easy fatigability associated with passing dark
coloured urine for two days. His systemic examination reveals muscle tenderness. His investigations
showed high blood urea (147 mg%), serum creatinine (2.4mol/L), creatine kinase (CK) (21,210 U/L) and
with a significant increase in urine myoglobin. Even he has no risk factors; he was diagnosed as
rosuvastatin induced rhabdomyolysis associated with acute renal failure. The drug was stopped on the
first day of admission and the patient was initiated on intravenous fluid with cautious monitoring of
serum electrolytes. On the following days, the level of creatine kinase and serum myoglobin returned
towards normal and consequently he was discharged without statins but on dietary therapy. On follow-
up evaluation, the patient was symptoms free, his serum creatinine was 0.7mol/L, whereas his LDL
cholesterol was 119mg/dL. The rosuvastatin induced rhabdomyolysis is discussed and the danger of its
use in low risk patients is emphasized.
Key Words:
Cytochrome P450, rhabdomyolysis, rosuvastatin.

INTRODUCTION

Statins are 3-hydroxy-3-methyl coenzyme A (HMG-
levels by 54%, while it increased HDL cholesterol by CoA) reductase inhibitors that have significant effects 13% after 96 weeks [4]. Like other statins, rosuvastatin on the plasma lipid and lipoprotein profile, lowering total is associated with a spectrum of adverse events and LDL cholesterol and triglyceride levels and raising ranging from mild to life-threatening. The most severe HDL cholesterol levels; currently they are the mainstay
adverse event is severe myopathy (ranges from of dyslipidemia management for the primary and myalgias to rhabdomyolysis), which can cause acute secondary prevention of cardiovascular disease.The renal failure; this adverse event usually associated with use of statins in randomized trials has demonstrated many risk factors. In this report we present a case of 30% reductions in atherosclerotic end points without rhabdomyolysis induced by low dose of rosuvastatin (10 serious morbidity [1]. Rosuvastatin is a competitive mg daily) in a 62-year-old Batticaloa man who had no inhibitor of the enzyme HMG-CoA reductase, having a obvious risk factor. mechanism of action similar, yet higher efficacy, to other statins [2]. The efficacy of rosuvastatin across its dose range of 10 to 40 mg is superior to that of other CASE REPORT
statins across their dose range,although the safety is similar [3]. Rosuvastatin 40 mg reduced LDL cholesterol A 62 year-old Batticaloa man admitted with one week history of bilateral thigh, back and shoulder pain and easy fatigability associated with passing dark coloured urine for two days. He denied the consumption of *Corresponding author. E-mail: selladuraipirasath81@g grapefruit juice or alcohol abuse and he hadn't had any exercise before this episode. There was no family Pirasath et al 269 history of muscle disease. The patient had history of reported [5]. Like other statins, rosuvastatin can cause diabetes mellitus (DM) type II, hypertension and life threatening rhabdomyolysis [1]. Our patient hypercholesterolemia. He had hypertension since for 20 presented with bilateral thigh back and shoulder pain and easy fatigability associated with passing dark urine. hypercholesterolemia for 2 years and had been His serum creatinine was higher than the baseline and followed up regularly by his physician in the clinic. his CK was greater than 20 times the upper limit of Current medications included metformin 500mg thrice normal. The incidence of rosuvastatin- induced daily orally (PO) and losartan 50mg once daily. His rhabdomyolysis is not known exactly but it was hypercholesterolemia presumed to be low [6], and similar to atrovastatin, atrovastatin 20 mg/ day for 2 years, but the patient was pravastatin, and simvastatin [6]; to our knowledge this is shifted to rosuvastatin 10 mg once daily PO during the the first reported case in Batticaloa and even in low last 2 months for better control of hypercholesterolemia. dose of Rosuvastatin (10mg). Although statin induced On examination the pulse was 84/min and the blood rhabdomyolysis has been reported at rates of 1 death pressure 150/95 mmHg. His systemic examination per 6.6million prescriptions [7], no deaths related to reveals muscle tenderness in bilateral thigh. The rosuvastatin induced rhabdomyolysis were reported in remaining of the examination was unremarkable. the literature [6]. Heerey et al. [8] estimated that Initial investigations showed hemoglobin level of 11.9 approximately 30% of all users of statins have g/ dL, total leucocyte count 8700/mL and platelets, concomitant prescribed drugs that can inhibit statin 479,000/uL; blood urea 147mg/dL, creatinine 2.4mg/dL, metabolism by hepatic cytochrome P450 (CYP) system, sodium 130.3 mEq/L and potassium 4.32 mEq/L, potentially leading to rhabdomyolysis. The factors that bicarbonate 23 mmol/L, Ca 2.3 mmol/L, blood sugar increase the risk of rosuvastatin induced myopathy or 130mg/dL. His myoglobin was elevated, 2694 ng/ml with a significant increase in urine myoglobin. The impairment, hypothyroidism, personal or family history creatine kinase (CK) level was markedly elevated of hereditary muscular disorders, previous history of (21,210 U/L).Aspartate aminotransferases (AST) was muscular toxicity with another statin or fibrate, 89 IU/L, alanine aminotransferase (ALT) 60 IU/L and consumption of grapefruit juice (more than 1 L per day), alkaline phosphatase 341 IU/L. Total bilirubin was alcohol abuse, being of Chinese or Japanese descent, 5mol/L, total proteins, 7.5 g/dL, and albumin, 4.0 g/dL, concomitant use of fibrates. This group of patients whereas PT and INR were normal. His fasting lipid should be given rosuvastatin with caution [5].Our patient had no obvious risk factors; he was 62 years old cholesterol, 119mg/dL; triglyceride, 155mg/dL. His and non alcoholic and nonsmoker; his baseline previous investigations during clinic follow up before creatinine was normal and the calculated creatinine clearance was normal. Rosuvastatin should be discontinued in patients with a creatine kinase level of seemed the most likely diagnosis; accordingly this drug more than 10 times the ULN with or without muscle was stopped at time of admission and intravenous fluids symptoms [5]. Liver transaminase levels should be (normal saline) given at 150 cc/hour with cautious assessed at baseline, at 12 weeks after the start of monitoring of serum electrolytes. Other medications therapy or an increase in dose, and at 6-month intervals were resumed. On the following days the level of thereafter. The dosage should be reduced or therapy creatine kinase and serum myoglobin declined toward withdrawn if liver transaminase levels exceed 3 times the normal value and consequently he was discharged the ULN.Because of the potential for rosuvastatin to 10 days after hospitalization without statins but on diet increase liver transaminase levels, it should be used therapy. At the time of discharge, his baseline with caution in patients with a history of liver disease or investigations are normal. On follow-up evaluation two alcohol abuse [9].Overall, persistent elevations in liver months after discharge the patient was symptom free; transaminase levels are reported in 0.1-0.4% of patients laboratory evaluation yielded CK of 212 U/L, serum taking rosuvastatin 5-40 mg [9]. Similarly, our patient creatinine of 0.7mg/L and LDL cholesterol of 119mg/dL. showed high transaminase level which was returned to normal after discontinuation of the drug. Although the exact mechanism of statin-induced rhabdomyolysis is DISCUSSION
unknown, the implicated mechanisms include the followings: first, the cholesterol synthesis blockage; Rosuvastatin is a relatively new cholesterol-lowering which makes the skeletal muscle-cell membranes drug in Sri Lanka as well as in other countries; although unstable due to low cholesterol content [10]. Second, highly efficacious, this new statin has generated prenylated protein abnormalities causing imbalances in considerable controversy regarding its safety. In intracellular protein messaging [11]. Third, coenzyme Canada as well as United States, many cases of rosuvastatin induced rhabdomyolysis have been respiratory function [12]. Rosuvastatin induced rhabdom 270 Int. J. Med.Med.Sci. yolysis in this patient is supported by the following: first, De Pinieux G, Chariot P, Ammi-Said M, et al. Lipid among the drugs used by the patient, there was no drug lowering drugs and mitochondrial function: Effects of HMG-CoA reductase inhibitors on serum ubiquinone myoglobin and CK were washed out from the blood and and blood lactate/ pyruvate ratio. Br. J. Clin. returned towards normal within few days after Pharmacol. 1996; 42: 333-337. discontinuation of rosuvastatin. In conclusion, although Flint OP, Masters BA, Gregg RE, Durham SK. Inhibition of cholesterol synthesis by squalene synthase considerable controversy regarding its safety; clinicians inhibitors does not induce myotoxicity in vitro. Toxicol should maintain an increased level of awareness of the Appl Pharmacol 1997; 145: 91-98. potential for muscle toxicity and rhabdomyolysis, which Heerey A, Barry M, Ryan M, Kelly A. the potential for associated with this new drug even with low dose. drug interactions with statin therapy in Ireland. Ir J. Accordingly, Emergent myalgias in patients under Med. Sci. 2000; 169: 176-9. rosuvastatin necessitate immediate testing of creatine Shepherd J, Vidt DG, Miller E, Harris S, Blasetto J. kinase and myoglobin to exclude life threatening rhabdomyolysis even with low dose. rosuvastatin-treated patients in a multinational clinical trial program. Cardiology 2007; 107: 433-43. Staffa JA, Chang J, Green L. Cerivastatin and reports of REFERENCES
fatal rhabdomyolysis. N. Engl. J. Med. 2002; 346: Stein EA, Amerena J, Ballantyne CM, et al. Long-term Antons KA, Williams CD, Baker SK, Phillips PS. Clinical efficacy and safety of rosuvastatin 40 mg in patients perspectives of statin-induced rhabdomyolysis. Am. J. with severe hypercholesterolemia. Am. J. Cardiol. Med. 2006; 119: 400-9. 2007; 100: 1387-96. Thompson PD, Clarkson P, Karas RH. Statin- rhabdomyolysis [Dear Health Care Professional associated myopathy. JAMA 2003; 289: 1681-90. letter]. Mississauga (ON): Astra Zeneca Canada Inc.; 2004 //napra.ca/pdfs/advisories/ crestorhc.pdf [accessed 2008 July 28]. Wilmington, DE; 2003. Brewer HB Jr. Benefit-risk assessment of rosuvastatin 10 to 40 milligrams. Am. J. Cardiol. 2003; 92: 23-29. Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N. Engl. J. Med. 2004; 350: 1495-1504.

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