Fenofibrate and Liver Enzyme Elevations
Yes, fenofibrate can increase liver enzymes, and this is a well-documented adverse effect that requires regular monitoring. 1
Incidence of Liver Enzyme Elevations
In pooled analysis of 10 placebo-controlled trials, ALT elevations >3 times the upper limit of normal occurred in 5.3% of patients taking fenofibrate at doses equivalent to 107-160 mg daily versus 1.1% of patients on placebo. 1
In an 8-week study, the incidence of ALT or AST elevations ≥3 times the upper limit of normal was 13% in patients receiving dosages equivalent to 107-160 mg fenofibrate daily, compared to 0% in those receiving dosages equivalent to 54 mg or less fenofibrate daily or placebo. 1
Abnormal liver function tests occurred in 7.5% of fenofibrate-treated patients versus 1.4% of placebo patients in double-blind controlled trials. 1
Increased ALT occurred in 3% versus 1.6% and increased AST in 3.4% versus 0.5% of fenofibrate versus placebo patients, respectively. 1
Clinical Significance and Monitoring Requirements
The FDA label states that increases in liver function tests were the most frequent events causing discontinuation of fenofibrate treatment, occurring in 1.6% of patients in double-blind trials. 1
Liver enzyme elevations are typically transient, minor, and asymptomatic in most cases. 2
The American Heart Association recommends that liver function tests should be monitored before starting fenofibrate, within 3 months after initiation, and every 6 months thereafter. 3
Post-marketing reports have documented cases of hepatitis and cirrhosis with fenofibrate use, though these are rare. 1
Absolute Contraindications Related to Liver Function
Fenofibrate is contraindicated in patients with active liver disease, including those with primary biliary cirrhosis and unexplained persistent liver function abnormalities. 1
Severe hepatic impairment is a contraindication for fenofibrate therapy. 4
Practical Management Algorithm
When initiating fenofibrate:
- Obtain baseline liver function tests (ALT, AST) before starting therapy. 3, 1
- Ensure patient does not have active liver disease or unexplained persistent liver function abnormalities. 1
During treatment:
- Recheck liver function tests within 3 months of initiation. 3
- Continue monitoring every 6 months during ongoing therapy. 3
- If ALT or AST rises to >3 times the upper limit of normal, consider dose reduction or discontinuation. 1
When combining with statins:
- The ACCORD trial showed no statistically significant differences in hepatic transaminase elevations with simvastatin-fenofibrate versus simvastatin alone, suggesting combination therapy does not substantially increase hepatotoxicity risk beyond monotherapy. 5
- However, the American Heart Association warns that combination therapy with statins and fibrates is associated with increased risk of abnormal transaminase levels. 3
Common Pitfalls to Avoid
Do not initiate fenofibrate in patients with unexplained baseline liver enzyme elevations—investigate and resolve these first. 1
Do not assume all liver enzyme elevations are benign—while most are transient and asymptomatic, rare cases of hepatitis and cirrhosis have been reported. 1
Do not neglect regular monitoring—the 3-month and 6-month follow-up schedule is essential for early detection of hepatotoxicity. 3
Do not continue fenofibrate if persistent, unexplained liver enzyme elevations develop during treatment. 1