Statins myopathy

Harper CR, Jacobson TA. The broad spectrum of statin myopathy from myalgia to rhabdomyolysis. Curr. Opin. Lipidol. 2007 18 401-408. 

The rate-limiting enzyme in cholesterol biosynthesis is HMGCR (Fig. 2). Statins inhibit the activity of this enzyme. It has been demonstrated in multiple studies that genetic variants in the HMGCR gene are important determinants for statin efficacy [69-75], Although it seems reasonable to assume that those polymorphisms would also alter risk of statin toxicity, Frudakis et al. failed to observe any association between HMGCR variants and statin myopathy in a... 

DA, Roden DM, Ingram C, Kitchner T, McCarty CA, Rotter JI, Krauss RM, Crawford DC, Wilke RA (2013) Exome scanning reveals RYR1 as a determinant for statin myopathy risk. Annual meeting of the American Society for Clinical Pharmacology and Therapeutics... 

Fernandez G, Spatz ES, Jablecki C, Phillips PS (2011) Statin myopathy a common dilemma not reflected in clinical trials. Cleve Clin J Med 78 393 103... 

R., Waldmann, H., Clemons, P.A., Sukhatme, V.P, and Mootha, V.K. (2011) A small-molecule screening strategy to identify suppressors of statin myopathy. ACS Chem. Biol., 6, 900-904. 

Venero CV, Thompson PD. Managing statin myopathy. Endocrinol Metab Clin North Am 2009 38(1) 121-36. 

Specific concomitant medications or consumptions (check specific statin package insert for warnings) fibrates (especially gemfibrozil, but other fibrates too), nicotinic acid (rarely), cyclosporine, azole antifungals such as itraconazole and ketoconazole, macrolide antibiotics such as erythromycin and clarithromycin, protease inhibitors used to treat Acquired Immune Deficiency Syndrome, nefazodone (antidepressant), verapamil, amiodarone, large quantities of grapefruit juice (usually more than 1 quart per day), and alcohol abuse (independently predisposes to myopathy)... 

Baseline CK should be obtained in all patients prior to starting statin therapy. Follow-up CK should only be obtained in patients complaining of muscle pain, weakness, tenderness, or brown urine. Routine monitoring of CK is of little value in the absence of clinical signs or symptoms. Patient assessment for symptoms of myopathy should be done 6 to 12 weeks after starting 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. 

Constipation occurs in fewer than 10% of patients taking statins. Other adverse effects include elevated serum aminotransferase levels (primarily alanine aminotransferase), elevated creatine kinase levels, myopathy, and rarely rhabdomyolysis. 

Patients receiving statins should have a fasting panel 4 to 8 weeks after the initial dose or dose changes. Liver function tests should be obtained at baseline and periodically thereafter based on package insert information. Some experts believe that monitoring for hepatotoxicity and myopathy should be triggered by symptoms. 

Statins, such as fluvastatin, may cause myalgia as a sign of myopathy. Patients are advised to report myalgia immediately. 

Simvastastin is a statin and there is an increased risk of myopathy when simvastatin is given with clarithromycin (macrolide). 

Skeletal muscle effects All statins have been associated with myalgia, myopathy (ie, muscle pain, tenderness, or weakness with creatine phosphokinase [CPK] values above 10 times the ULN), and rhabdomyolysis. Factors that may predispose patients... 

Action HMG-CoA reductase inhibitor Dose 5-40 mg PO daily max 5 mg/d w/cyclosporine, 10 mg/d w/gemfibrozil or CrCl <30 mL/min (avoid Al-/Mg-based antacids for 2 h after) Caution [X, /-] Contra Active Uvct Dz, unej lained t LFT Disp Tabs SE Myalgia, constipation, asthenia, abd pain, N, myopathy, rarely rhabdomyolysis Interactions t Effects OF warfarin t risk of myopathy W/ cyclosporine, fibrates, niacin, statins EMS t Effects of warfarin concurrent EtOH use can t risk of liver tox Asian pts have an t risk of advise effects OD Unlikely to cause life-threatening Sxs... 

Skeletal muscle myopathy often leads to release of CK of the MM type. Rhabdomyolysis Is one of the major side effects of treatment with the cholesterol-lowering drugs the statins. 

Phillips PS. Ezetimibe and statin-associated myopathy. Ann Intern Med 2004 141(8) 649. 

Rhabdomyolysis is a problem with several lipid-lowering drugs (SEDA-13, 1325 SEDA-13, 1328 SEDA-13, 1330 SEDA-19, 409), especially when they are used in combination (37). In individuals with pre-existing renal insufficiency this can lead to an earlier need for chronic dialysis (38). All statins can cause myopathy and rhabdomyolysis, but not all statins are alike. For example, the evidence to date, based on almost 2 decades of experience, points to an extremely low risk of myopathy and rhabdomyolysis with lovastatin, and lovastatin 20 mg tablets are being considered for non-prescription availability in several countries (39). Furthermore, muscle adverse effects do not necessarily occur after a change from one statin to another (40). Interactions between various hypolipidemic drugs and other drugs also sometimes cause rhabdomyolysis (SEDA-18, 426). For instance, itraconazole markedly increases plasma concentrations of lovastatin, and in one subject plasma creatine kinase was increased 10-fold within 24 hours of administration of this combination (41). 

Exercise-induced muscle pain, without myopathy and a rise in creatine kinase activity, can probably be caused by statins. This has been described in seven patients with heterozygous familial hypercholesterolemia and consisted of pain during exercise and cramps in the following hours (54). 

Carvalho A A, Lima UW, Valiente RA. Statin and fibrate associated myopathy study of eight patients. Arq Neuro-Psiquiatria 2004 62(2A) 257-61. 

Phillips PS, Haas RH, Bannykh S, Hathaway S, Gray NL, Kimura BJ, Vladutiu GD, England JDScripps Mercy Clinical Research Center. Statin-associated myopathy with normal creatine kinase levels. Ann Intern Med 2002 137(7) 581-5. 

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