From the Guidelines
Zetia (ezetimibe) can affect liver function, particularly when used in combination with statin medications, and is not recommended in patients with moderate to severe hepatic impairment. According to the 2022 ACC expert consensus decision pathway on the role of nonstatin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk 1, ezetimibe may cause persistent elevations in hepatic transaminases, and monitoring of hepatic transaminases is recommended before and during treatment, especially when used in combination with statin therapy.
Some key points to consider when evaluating the potential liver effects of Zetia include:
- The mechanism of action of ezetimibe, which inhibits the NPC1L1 protein and reduces cholesterol absorption in the small intestine, may contribute to its potential liver effects 1
- The FDA-approved indication for ezetimibe includes a warning about the potential for liver enzyme elevations, particularly when used in combination with statin therapy 1
- Clinical trials, such as the IMPROVE-IT trial, have demonstrated the efficacy of ezetimibe in reducing LDL-C and cardiovascular outcomes, but also highlighted the importance of monitoring liver function during treatment 1
It is essential to weigh the benefits of Zetia in reducing LDL-C and cardiovascular risk against the potential risks to liver function, particularly in patients with pre-existing liver disease or those taking concomitant medications that may increase the risk of liver injury. Patients should be closely monitored for signs of liver dysfunction, such as unusual fatigue, abdominal pain, dark urine, or yellowing of the skin or eyes, and healthcare providers should adjust treatment accordingly.
From the FDA Drug Label
Liver Enzyme Abnormalities and Monitoring: Increases in serum transaminases have been reported with use of ezetimibe tablets. Perform liver enzyme testing as clinically indicated and consider withdrawal of ezetimibe tablets if increases in ALT or AST ≥3 X ULN persist. Inform patients that ezetimibe tablet may cause liver enzyme elevations [see Warnings and Precautions (5. 2)].
Zetia (ezetimibe) can affect liver function, as indicated by increases in serum transaminases. Liver enzyme testing is recommended, and ezetimibe should be withdrawn if significant increases in ALT or AST persist 2.
From the Research
Zetia and Liver Function
- Zetia (ezetimibe) is a lipid-lowering agent that has been studied for its effects on liver function in various patient populations.
- A study published in 2009 3 found that ezetimibe was effective in treating hypercholesterolemia in liver transplant recipients with few side effects and no significant interactions with immunosuppressive regimens.
- However, another study published in 2008 4 noted that ezetimibe has been associated with mild elevations of liver transaminases, mainly in combination with a statin.
- A randomized controlled trial published in 2014 5 found that ezetimibe improved hepatic fibrosis but increased hepatic long-chain fatty acids and HbA1c in patients with non-alcoholic fatty liver disease (NAFLD).
- A study published in 2022 6 found that impaired hepatic function significantly increased the systemic exposure of ezetimibe and its active metabolites, and that the conversion of ezetimibe to its active metabolite decreased concentration-dependently in hepatic failure rat liver S9 fractions.
- Another study published in 2011 7 found that long-term ezetimibe therapy improved NAFLD-related metabolic parameters, biochemical parameters, and histological features of steatosis grade, necroinflammatory grade, ballooning score, and NAFLD activity score in patients with NAFLD.
Key Findings
- Ezetimibe may be associated with mild elevations of liver transaminases, particularly when used in combination with a statin 4.
- Ezetimibe may improve hepatic fibrosis but increase hepatic long-chain fatty acids and HbA1c in patients with NAFLD 5.
- Impaired hepatic function may increase the systemic exposure of ezetimibe and its active metabolites 6.
- Long-term ezetimibe therapy may improve NAFLD-related metabolic and histological abnormalities 7.
Liver Function and Ezetimibe
- The effects of ezetimibe on liver function may vary depending on the patient population and the presence of underlying liver disease 3, 4, 5, 6, 7.
- Further studies are needed to fully understand the effects of ezetimibe on liver function and to determine its safety and efficacy in patients with liver disease.