When should ezetimibe be stopped?

When to Stop Ezetimibe

Discontinue ezetimibe if persistent ALT elevations ≥3 times the upper limit of normal occur, particularly when coadministered with a statin. 1

Mandatory Discontinuation Criteria

Hepatotoxicity

• Stop ezetimibe immediately if ALT or AST levels persistently exceed 3 times the upper limit of normal (ULN). 1
• Monitor hepatic transaminases before initiation and as clinically indicated during treatment, especially when combined with statins. 1
• Serious hepatocellular drug-induced liver disease has been reported, requiring prompt withdrawal when significant liver test abnormalities develop. 2

Pregnancy and Breastfeeding

• Discontinue ezetimibe when pregnancy is recognized unless benefits clearly outweigh fetal risks. 1, 3
• Stop ezetimibe at least 1 month (preferably 3 months) before attempted conception. 1
• Discontinue during breastfeeding, as it is unknown whether ezetimibe passes into breast milk. 3
• Lipid-lowering therapy may be resumed after completion of breastfeeding. 1

Severe Allergic Reactions

• Immediately discontinue if symptoms of serious allergic reaction occur: swelling of face/tongue/throat, difficulty breathing, severe skin rash, hives, or anaphylaxis. 3

Clinical Scenarios Requiring Reconsideration

Muscle-Related Adverse Effects

• Stop ezetimibe if unexplained muscle pain, tenderness, weakness, or elevated creatine kinase occurs, particularly when combined with statins. 3
• While myopathy risk appears low with ezetimibe monotherapy, case reports exist and warrant discontinuation if symptoms develop. 4
• Rhabdomyolysis, though rare, requires immediate cessation. 3

Achievement of Treatment Goals

• Consider discontinuing or de-escalating therapy if LDL-C goals are consistently achieved and maintained (e.g., LDL-C <70 mg/dL in very high-risk patients, <100 mg/dL in moderate-risk patients). 1
• However, most patients require lifelong therapy for sustained cardiovascular risk reduction. 1

Drug Interactions Requiring Discontinuation

• Stop ezetimibe if cyclosporine levels become difficult to manage, as ezetimibe increases cyclosporine exposure and cyclosporine significantly increases ezetimibe levels. 5
• Exercise caution and consider discontinuation if severe drug interactions develop with other medications. 3

Special Population Considerations

Renal Impairment

• No dosage adjustment or discontinuation required for mild-to-severe renal insufficiency, as ezetimibe pharmacokinetics are not significantly affected. 5

Hepatic Impairment

• Ezetimibe is not recommended in moderate-to-severe hepatic impairment; discontinue if liver function deteriorates significantly. 1

End-Stage Renal Disease and Symptomatic Heart Failure

• Limited evidence exists for ezetimibe use in patients on maintenance hemodialysis or with symptomatic heart failure; individualized assessment is needed, and discontinuation may be appropriate if no clear benefit is demonstrated. 1

Monitoring Parameters to Guide Discontinuation Decisions

• Obtain baseline hepatic transaminases before initiation; monitor as clinically indicated during treatment. 1
• Check lipid panels 4-12 weeks after initiation to assess response. 1, 3
• Monitor for adverse effects including gastrointestinal disturbances, myalgia, hepatic dysfunction, headache, and fatigue. 1
• Assess adherence to medications and lifestyle modifications at each visit. 1

Common Pitfalls to Avoid

• Do not continue ezetimibe if persistent transaminase elevations ≥3× ULN occur, even if asymptomatic. 1
• Do not assume ezetimibe is always safe in combination therapy—monitor for additive hepatotoxicity and myopathy risk when combined with statins. 1, 4
• Do not forget to discontinue before pregnancy—unlike some medications where timing is flexible, lipid-lowering therapy should stop well before conception. 1
• Do not abruptly stop without considering cardiovascular risk—in patients with established ASCVD, discontinuation may increase risk of recurrent events unless LDL-C goals are maintained through other means. 1