Rhabdomyolysis secondary to lovastatin therapy

Abstract

We report a case of lovastatin-induced rhabdomyolysis and resulting life-threatening renal failure. Lovastatin, a hypocholesterolemic agent, decreases endogenous cholesterol synthesis by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.88). This agent has been implicated in causing rare serious side effects in various clinical settings; however, the mechanism of these adverse reactions is not understood. The clinical course of our patient was characterized by profound muscle weakness with marked increases in serum creatine kinase and myoglobin. Light- and electron-microscopic studies of skeletal muscle of our patient demonstrated a noninflammatory myopathy suggestive of ongoing rhabdomyolysis with vacuolization and focal degeneration of myocytes. The patient's symptoms and the laboratory values referable to rhabdomyolysis resolved after discontinuation of the drug. We speculate that the rhabdomyolysis was due to mitochondrial damage secondary to inadequate synthesis of coenzyme Q and heme A, members of the electron-transport system of the inner mitochondrial membrane.

Effect of Coenzyme Q10Supplementation in Statin-Treated Obese Rats

“…Statins are the most efficient drugs for reducing plasma cholesterol level, and generally well-tolerated ( Golomb and Evans, 2008 ). The most common adverse effects of statins are liver and muscle damage including elevated liver enzyme levels in serum, myopathy, myositis and rhabdomyolysis ( Manoukian et al ., 1990 ; Nakahara et al ., 1998 ; Delbosc et al ., 2002 ). As a result of a common biosynthesis pathway, both cholesterol and Coenzyme Q 10 (CoQ 10 ) biosynthesis are decreased by statin treatment ( Diebold et al ., 1994 ; Nakahara et al ., 1998 ; Satoh and Ichihara, 2000 ; Berthold et al ., 2006 ).…”

Ontology-based systematical representation and drug class effect analysis of package insert-reported adverse events associated with cardiovascular drugs used in China

“…All these mechanisms are likely interconnected. For example, coenzyme Q is a member of the electron transport system of the inner mitochondrial membrane where it converts the energy in carbohydrates and fatty acids into ATP to drive cellular machinery and synthesis 84 , and treatment with Coenzyme Q10 significantly affects cholesterol production 85 . A recent report indicates that Coenzyme Q10 protects against statin-induced myotoxicity in zebrafish larvae 86 .…”

Effects of HMG-CoA reductase inhibitors on growth and differentiation of cultured rat skeletal muscle cells

“…Concern has risen about skeletal muscle during treatment with these drugs, ranging from asymptomatic elevations of serum creatine kinase (CK) activity and myopathy to rhabdomyolysis [6][7][8][9][10][11][12][13][14]. Myopa thy (muscle tenderness and CK levels exceeding more than 10 times the upper limit of normal) has been found espe cially during combination therapy with gemfibrozil [6][7][8][9].…”

“…Myopa thy (muscle tenderness and CK levels exceeding more than 10 times the upper limit of normal) has been found espe cially during combination therapy with gemfibrozil [6][7][8][9]. Rhabdomyolysis has been observed in combinations with erythromycin, niacin or cyclosporin [10][11][12][13][14]. Cyclosporin of HMG-CoA reductase in hibitors due to inhibition of their biliary excretion [1 1], in animals, severe muscle damage can be induced by HMG-CoA reductase inhibitors [15][16][17][18] especially when comwith cyclosporin [15].…”