Myopathy ezetimibe

Skeletal muscle effects In clinical trials, there was no excess of myopathy or rhabdomyolysis associated with ezetimibe compared with the relevant control arm (placebo or HMG-CoA reductase inhibitor alone). However, myopathy and rhabdomyolysis are known adverse reactions to HMG-CoA reductase inhibitors and other lipid-lowering drugs. 

Ezetimibe/Simvastatin (Vytorin) [Antilipemic/HMG CoA Reductose Inhibitor] Uses H rp cholest olemia Action X Absorption of cholesterol phytost ol w/ HMG-CoA reductase inhibitor Dose 10/10-10/80 mg/d PO w/ cyclosporine or danazol 10/10 mg/d max w/ amio-darone or verapamil 10/20 mg/d max -1- w/ sev e renal insuff Caution [X, -] w/ CYP3A4 inhibitors (Table VI-8), gemfibrozil, niacin >lg/d, danazol, amiodarone, verapamil Contra PRG/lactation livCT Dz, t LFTs Disp Tabs SE HA, GI upset, myalgia, myopathy (muscle pain, weakness, or tendOTiess w/ CK 10 x ULN, rhab-domyolysis), Hep, Infxn Interactions t Risk of myopathy W7 clarithromycin, erythromycin, itraconazole, ketoconazole EMS None OD Sxs unknown symptomatic and supportive... 

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

Perez-Calvo J, Civeira-Murillo F, Cabello A. Worsening myopathy associated with ezetimibe in a patient with McArdle disease. Q J Med 2005 98(6) 461-2. 

Ezetimibe is usually used in combination with simvastatin. Patients should be monitored for signs of myopathy. Monitor transaminases. The extended therapeutic effect due to enterohepatic recycling may be reduced in obstructive jaundice. 

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]. 

Ezetimibe rarely can cause allergic reactions. It has been associated with myopathy, more commonly in association with statins but also when used as monotherapy. The mechanism for this adverse effects is unknown. The safety of ezetimibe during pregnancy has not been established. Since all statins are contraindicated in pregnant and nursing women, combination products containing ezetimibe and a statin should not be used by women in childbearing years in the absence of contraception. 

Ezetimibe generaiiy is weii toierated. The most common adverse effects are listed above. Whenever ezetimibe is used in combination with an HMGRi, the incidence of myopathy or rhabdomyolysis does not increase above that seen with HMGRI monotherapy (15,21). 

Ezetimibe does not appear to have adverse pharmacokinetic interactions with atorvastatin, fluvastatin, iovastatin, rosuvastatin or simvastatin. However, some evidence suggests that concurrent use may increase the risk of myopathy. 

In a three-arm study, patients were given simvastatin 80 mg daily, simvastatin 80 mg daily with ezetimibe 10 mg daily, or simvastatin 40 mg daily with ezetimibe 10 mg daily. No difference in adverse events was noted between each of the 3 groups and there were no significant elevations in creatine kinase. No cases of myopathy or rhabdomyolysis occurred, and the combination was well-tolerated. In another study, ezetimibe 0.25 mg, 1 mg or 10 mg daily had no effect on the pharmacokinetics of simvastatin 10 mg daily, when both were given for 14 days. In addition, 10 and 20-mg doses of simvastatin were well-tolerated in combination with ezetimibe. ... 

Simard C, Poirier P. Ezetimibe-associated myopathy in monotherapy and in conbination with a 3-hydroxy-3-methylglutaryl coen me A reductase inhibitor Can J Cardiol ( 006) 22,141-44. 

A case report describes a 48-year-old man taking ezetimibe 10 mg daily, and rosuvastatin 5 mg on alternate days, who developed rhabdomyolysis within 3 weeks of starting to drink 200 mL of pomegranate juice twice weekly. Although the patient had been stable taking ezetimibe with rosuvastatin for 15 months he had a history of myopathy with statins and had an elevated creatine kinase before statin treatment had started. ... 

However, in a major placebo-controlled trial of ezetimibe 10 mg/day + simvastatin 20 mg/day in 9270 patients with chronic kidney disease, the SHARP trial has shown a significant 17% reduction in major cardiovascular events [6 ]. Although treatment did not prevent progression of renal disease nor reduce total mortality, it showed that it is safe to treat patients with chronic kidney disease with these two drugs in combination. Myopathy did not occur more frequently than among controls. 

The authors of a major review of rosuvastatin concluded that its adverse reaction profile resembles that of other commonly used statins [34 ]. Increments in fiver enzymes are in most cases minor and of minimal concern, renal dysfunction is quite uncommon, myopathy is unusual, and rhab-domyolysis is rare. Interactions with other drugs are fisted but no new information given. Combinations with fenofibrate, omega-3 fatty acids, ezetimibe, rifampicin, and clopidogrel appear to be safe. 

Musculoskeletal Serious myopathy has been studied in a systematic review of PubMed hsted studies of ezetimibe alone or combined with a statin. The frequency of musculoskeletal disorders was identical with placebo or, in the case of combination therapy, with the... 

Slim H, Thompson PD. Ezetimibe-related myopathy a systematic review. J Qin lipi-dol 2008 2(5) 328-34. 

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