What cholesterol medications do not affect liver enzymes, specifically those that do not cause elevated liver enzymes (transaminases) or hepatic impairment?

From the Guidelines

Bile acid sequestrants, such as colesevelam, are a suitable option for managing cholesterol without significantly affecting liver enzymes, as they work locally in the intestine and are not systemically absorbed 1. When considering cholesterol medications that do not affect liver enzymes, several options are available.

• Bile acid sequestrants, including colesevelam, cholestyramine, and colestipol, are not absorbed systemically and thus do not interact with the liver, making them a viable choice for patients with liver concerns.
• These medications work by binding bile acids in the intestine, which in turn increases the demand for cholesterol in the liver, leading to increased clearance of LDL particles from the blood and a reduction in serum LDL-C levels.
• The dosing for colesevelam, for example, can be 6 tablets orally once daily or 3 tablets orally twice daily, taken with a meal and liquid, and it has been shown to reduce LDL-C by 15% as monotherapy and by an additional 10%-16% when used in combination with low- to moderate-intensity statin therapy 1.
• It is essential to monitor triglyceride levels and be aware of potential gastrointestinal side effects and interactions with other medications when using bile acid sequestrants.
• Other options like ezetimibe and PCSK9 inhibitors also have minimal impact on liver enzymes but may have different side effect profiles and administration routes.
• Ultimately, the choice of medication should be based on individual patient needs, including their cholesterol profile, liver function, and potential for drug interactions, with regular monitoring to ensure safety and efficacy.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Cholesterol Medications with Minimal Liver Enzyme Impact

• Ezetimibe is a selective cholesterol absorption inhibitor that has been shown to reduce low-density lipoprotein cholesterol (LDL) by 15-20% without affecting liver enzymes significantly 2, 3.
• In a study of liver transplant recipients, ezetimibe was found to be effective in reducing LDL levels with minimal side effects and no significant impact on liver enzymes 3.
• PCSK9 inhibitors, such as evolocumab and alirocumab, have also been shown to be effective in reducing LDL levels with minimal side effects, including minimal impact on liver enzymes 4, 5.
• A meta-analysis of randomized trials found that PCSK9 inhibitors were more effective than ezetimibe in reducing LDL levels in patients not receiving statins, with no significant difference in liver enzyme impact 6.

Mechanism of Action

• Ezetimibe works by inhibiting the absorption of biliary and dietary cholesterol from the small intestine, which reduces the amount of cholesterol available for absorption into the bloodstream 2.
• PCSK9 inhibitors work by binding to and inhibiting the PCSK9 protein, which is involved in the regulation of LDL receptor expression on the surface of liver cells, leading to increased clearance of LDL from the bloodstream 4, 5.

Safety and Efficacy

• Ezetimibe has been shown to be safe and effective in reducing LDL levels in patients with primary hypercholesterolemia, including those with statin intolerance 2, 3.
• PCSK9 inhibitors have also been shown to be safe and effective in reducing LDL levels in patients with hypercholesterolemia, including those with statin intolerance 4, 5, 6.