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serum ck elevation before symptoms clinical features myalgias type of discomfort pain; cramp sensation; muscle tenderness pain present at rest; increased with exercise may occur with normal ck progress to myoglobinuria unless drug stopped weakness myoglobinuria recovery days to months after stopping drug laboratory serum ck myopathy high; 1 of patients taking statins myalgias may be normal pathology scattered necrotic muscle fibers fibric acid derivatives fibrates specific drugs clofibrate; bezafibrate; ciprofibrate; clofibrate; gemfibrozil primary metabolism renal epidemiology frequency 6 cases per 10,000 patients relative risk of myopathy in fibrate users vs controls 42x 6 increased risk renal failure nephrotic syndrome drugs, concurrent probenecid; furosemide; statins onset after 2 to 3 months of treatment associated cardiomyopathy biochemistry reduced fatty acid branched chain amino acid oxidation reduced carnitine palmitoyl transferase activity hmg-coa reductase inhibitors statins 9 drugs all statins associated with myopathic disorders lovastatin; simvastatin; pravastatin; fluvastatin; atorvastatin; cervistatin relative risks increased incidence of myopathy when compared to controls 6 8x statin relations higher doses used statins with longer half life relative toxicity atorvastatin pravastatin simvastatin lovastatin fluvastatin correlates with drug half-life statins are given with drugs that inhibit metabolism in liver gemfibrozil, niacin, cyclosporine; azoles; diltiazem; erythromycin; colchicine organ failure hepatobiliary dysfunction; renal failure cytochrome p450 polymorphisms with reduced activity except pravastatin rosuvastatin slco1b1 encodes organic anion-transporting polypeptide, oatp1b1 regulates hepatic uptake of statins odds ratio for simvastatin myopathy with non-coding cc snp polymorphism 16.
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