Yes, Zetia (ezetimibe) can cause liver damage, although it is very rare. Monitor liver enzymes for the development of serious toxic hepatitis and consider ezetimibe discontinuation if it develops. Perform liver tests during ezetimibe initiation and regularly thereafter and consider withdrawal of ezetimibe and/or the statin (if coadministered) should an increase in ALT or AST ≥3 X upper limit of normal (ULN) persist.

Case reports describe instances of serious hepatocellular drug-induced liver disease after a few months of ezetimibe treatment (10 mg daily). One involved a 56-year-old woman with no change in medication for the past 3 years (she was only taking omeprazole and bisoprolol), with very low alcohol intake, who developed painless jaundice and pruritus after 4 months of ezetimibe. Laboratory tests showed no evidence of other causes, and four weeks after stopping ezetimibe her jaundice and pruritus resolved and her laboratory results were completely normal.
Other case studies detailing significant liver injury with ezetimibe have been published: including one that was cholestatic, one hepatocellular, and two that were drug-induced autoimmune hepatitis; three of them were associated with atorvastatin. Patients with acute toxic hepatocellular damage are at high risk of acute liver failure.

Ezetimibe (Zetia) is generally well tolerated with upper respiratory tract infections, diarrhea, joint or extremity pain, and sinusitis the most common side effects reported. Significant liver function abnormalities, such as ≥3 X the upper limit of normal [ULN]) in hepatic transaminase levels have been reported in up to 1% of people receiving ezetimibe or 1.3% for those treated with ezetimibe plus a statin. These changes were generally asymptomatic, not associated with cholestasis, and returned to baseline after discontinuation of therapy or with continued treatment.