What is the incidence of myopathy associated with Ezetimibe (Zetia)?

From the Guidelines

The incidence of Zetia (ezetimibe) myopathy is rare, with cases reported when used alone or in combination with statin therapy, as noted in the 2022 ACC expert consensus decision pathway 1. When considering the use of Zetia, it's essential to weigh the benefits of LDL-cholesterol lowering against the potential risks, including myopathy. The mechanism of action of Zetia, which inhibits the NPC1L1 protein and reduces cholesterol absorption in the small intestine, differs from that of statins, which may contribute to its lower risk of myopathy when used as monotherapy 1. Key points to consider regarding Zetia and myopathy include:

• The risk of myopathy with Zetia alone is very low, occurring in less than 2% of patients 1.
• When Zetia is combined with statins, the risk of myopathy may increase slightly compared to statin therapy alone 1.
• Patients should be aware of potential muscle symptoms, including pain, tenderness, or weakness, particularly when Zetia is used alongside statins or in patients with predisposing factors 1.
• Regular monitoring is not typically required for Zetia monotherapy, but patients should report any unexplained muscle symptoms to their healthcare provider promptly 1. Overall, the benefits of Zetia in lowering LDL-cholesterol and reducing the risk of atherosclerotic cardiovascular disease (ASCVD) events, as demonstrated in trials such as IMPROVE-IT 1, should be carefully balanced against the potential risks, including myopathy, to ensure optimal patient outcomes.

From the FDA Drug Label

5.3 Myopathy/Rhabdomyolysis Ezetimibe tablets may cause myopathy [muscle pain, tenderness, or weakness associated with elevated creatine kinase (CK)] and rhabdomyolysis [see Adverse Reactions (6. 1)]. In post-marketing reports, most patients who developed rhabdomyolysis were taking a statin or other agents known to be associated with an increased risk of rhabdomyolysis, such as fibrates. If myopathy is suspected, discontinue ezetimibe tablets and other concomitant medications, as appropriate

The incidence of myopathy is not explicitly stated in the provided drug labels. However, it is mentioned that ezetimibe tablets may cause myopathy and rhabdomyolysis, particularly when used in combination with a statin or other agents known to be associated with an increased risk of rhabdomyolysis.

• Myopathy and rhabdomyolysis are potential risks associated with ezetimibe tablets, especially when used with other medications.
• The exact incidence of myopathy is not provided in the drug labels 2 2.

From the Research

Incidence of Zetia Myopathy

• The incidence of musculoskeletal disorders in clinical trials using ezetimibe alone or in combination with statins is identical to placebo or the statin alone, respectively 3.
• Only six case reports of possible ezetimibe-associated myopathy were identified in a systematic review 3.
• Two cases of myopathy associated with ezetimibe are reported, one with ezetimibe monotherapy and the other with ezetimibe added to atorvastatin 4.
• The mechanism by which ezetimibe could cause muscle pain is not known 4.
• Ezetimibe's side-effect profile resembles that of placebo when given as monotherapy or in combination with statins 5.

Comparison with Other Lipid-Lowering Agents

• Statins, ezetimibe, and bile acid-binding resins can be used individually or in combination for lowering low-density lipoprotein cholesterol (LDL-C) levels 6.
• The addition of a bile acid sequestrant or ezetimibe to a statin produces additional LDL-C reduction allowing many patients to reach LDL-C targets 6.
• Ezetimibe has a role as monotherapy for patients who require modest LDL reductions or cannot tolerate other lipid-lowering agents 5.
• In combination therapy with a statin, ezetimibe is used in patients who cannot tolerate high statin doses or in those who need additional LDL reductions despite maximum statin doses 5.