Fenofibrate Can Cause Elevated Liver Function Tests
Yes, fenofibrate commonly causes elevated liver function tests (LFTs), with abnormal liver function tests occurring in 7.5% of patients taking fenofibrate compared to 1.4% on placebo in clinical trials. 1
Evidence of Hepatotoxicity with Fenofibrate
According to the FDA label, increases in liver enzymes were the most frequent adverse events causing discontinuation of fenofibrate treatment in 1.6% of patients in double-blind trials 1
In a pooled analysis of 10 placebo-controlled trials, increases to >3 times the upper limit of normal in ALT occurred in 5.3% of patients taking fenofibrate at doses equivalent to 107-160 mg daily versus 1.1% of patients treated with 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 1
Post-marketing reports have identified hepatitis and cirrhosis as adverse reactions with fenofibrate use, though causality cannot always be definitively established 1
Monitoring Recommendations
The FDA label for fenofibrate specifically warns about hepatotoxicity, stating: "Serious drug-induced liver injury, including liver transplantation and death, has been reported with fenofibrate" 1
Monitor patient's liver function including serum ALT, AST, and total bilirubin at baseline and periodically for the duration of therapy 1
Discontinue fenofibrate if signs or symptoms of liver injury develop or if elevated enzyme levels persist 1
For patients on chronic fenofibrate therapy, regular laboratory monitoring (every 3-6 months) is recommended, assuming no abnormalities in laboratory test results 2
For elevations less than 3-fold the upper limit of normal, repeat testing should be done in 2-4 weeks 2
For significant elevations in liver enzymes (≥3-fold the upper limit of normal), close monitoring, repeat testing in 2-4 weeks, and dose decrease as needed are recommended 2
Risk Factors for Fenofibrate-Induced Liver Injury
Risk factors for fenofibrate-induced elevation of liver function tests include higher BMI, elevated baseline serum triglycerides, elevated baseline ALP, male sex, and elevated baseline gamma-GTP levels 3
Patients with these risk factors should be monitored more carefully for potential hepatotoxicity 3
Severity and Presentation of Liver Injury
While most cases of fenofibrate-induced liver injury are mild and reversible, severe cases have been reported 4
In a study by the Drug-Induced Liver Injury Network, 7 cases of liver injury attributed to fenofibrate were identified, with 2 patients experiencing severe outcomes (one requiring liver transplantation and one developing chronic injury resulting in death) 4
Liver injury can occur with variable latency (5-56 weeks), enzyme elevation patterns (hepatocellular, mixed, or cholestatic), and histological findings 4
Rapid onset of liver injury has been reported, with one case developing within 48 hours after the first dose of fenofibrate 5
Clinical Implications and Management
Jaundice or abnormal laboratory tests during fenofibrate therapy should trigger prompt discontinuation of the medication 4
For persistent elevations during a 12-month period or a decline in serum albumin below the normal range in a patient with normal nutritional status, consultation with gastroenterology should be considered 2
Chronic liver injury can occur, with some cases showing reduction in the number of interlobular bile ducts and persistent elevation of liver enzymes even after discontinuation of fenofibrate 6
When using fenofibrate in combination with statins, there is an increased risk of myopathy, particularly with gemfibrozil, but the combination of fenofibrate with statins does not appear to significantly increase the risk of hepatotoxicity beyond that of fenofibrate alone 2
In conclusion, fenofibrate can cause elevated liver function tests ranging from mild, asymptomatic elevations to severe hepatotoxicity. Regular monitoring of liver function is essential, and the drug should be discontinued if significant or persistent elevations occur.