Rhabdomyolysis statin therapy

Fibrates are the most effective triglyceride-lowering agents and also raise HDL cholesterol levels. Combination therapy with a fibrate, particularly gemfibrozil, and a statin has been found to increase the risk for myopathy. Of the 31 rhabdomyolysis deaths reported with cerivastatin use, 12 involved concomitant gemfibrozil.25 Therefore, more frequent monitoring, thorough patient education, and consideration of factors that increase the risk as reviewed previously should be considered. 

At this time in clinical practice, the role of fibrates is particularly in combination therapy with a statin. Monitoring of creatine phosphokinase levels is appropriate because of the very small, although increased risk of rhabdomyolysis. 

The rate of myopathy with a statin alone in the general population is 0.1-0.5% and 0.2-2.5% with combination therapy. Rhabdomyolysis is very rare at 0.02-0.04%. However, the latter carries a significant morbidity and mortality. In a review of Food and Drug Administration (FDA) reports published in 2002, there were 38 deaths in 631 patients (6.3%) [31]. Pravastatin and fluvastatin have been less frequently implicated in fatal cases of rhabdomyolysis [31]. It is postulated that the more hepatoselective hydrophilic statins, such as pravastatin, are less likely to penetrate muscle cells than are lipophilic statins, and therefore represent a lower risk for myopathy, particularly in the event of an interacting drug increasing their blood levels to within the toxic range [26, 32]. 

ATORVASTATIN, SIMVASTATIN MACROLIDES Macrolides may t levels of atorvastatin and simvastatin the risk of myopathy t over 10-fold when eiythromycin is co-administered with a statin Macrolides inhibit CYP3A4-mediated metabolism of atorvastatin and simvastatin. Also, erythromycin and clarithromycin inhibit intestinal P-gp, which may t the bioavailability of statins Avoid co-administration of macrolides with atorvastatin or simvastatin (temporarily stop the statin if the patient needs macrolide therapy). Manufacturers also recommend that patients be warned to look for the early signs of rhabdomyolysis when other statins are co-ingested with macrolides... 

Ezetimibe is used for secondary prevention against established atherosclerotic CVD to achieve an optimal atherogenic cholesterol level in patients with intolerance to high-doses of statins. It can further be used in combination with statins to achieve lower LDL-C levels in very-high-risk patients [59]. Ezetimibe inhibits the Niemann-Pick Cl-Like 1 (NPClLl)-dependent intestinal cholesterol absorption in the apical brush border membrane of jejuna enterocytes [14], and thus it only moderately lowers LDL-C (12-25 %) [60]. Meanwhile, common adverse effects associated with ezetimibe therapy include gastrointestinal disturbances, while infrequent adverse effects such as rash, angioedema, anaphylaxis, hepatitis, cholelithiasis, cholecystitis, thrombocytopenia, raised creatine kinase, myopathy, and rhabdomyolysis may occur [46]. 

The classification and management of muscle disorders due to statins are beginning to become clearer. It is now recognized that as many as 10% of patients who take a statin will develop muscle sjrnip-toms of varying severity. Myalgia remains the main therapeutic problem, and although it is not a major health concern, it occurs with sufficient frequency to affect adherence to therapy. However, most reviews of adverse effects focus on the much rarer myopathy or the very rare but potentially fatal rhabdomyolysis. 

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