Management of Fenofibrate in Patients with Transaminitis
Fenofibrate should be discontinued if liver transaminases are elevated to >3 times the upper limit of normal (ULN) or if there are signs of clinically significant liver toxicity. 1
Fenofibrate and Liver Function
- Serious drug-induced liver injury (DILI), including cases requiring liver transplantation and resulting in death, have been reported with fenofibrate use 1
- Fenofibrate at doses equivalent to 107-160 mg daily has been associated with increases in serum AST or ALT, with the incidence of transaminase elevations potentially being dose-related 1
- In clinical trials, increases to >3 times the ULN in ALT occurred in 5.3% of patients taking fenofibrate compared to 1.1% of patients on placebo 1
- Liver injury from fenofibrate can occur with variable latency (5-56 weeks) and presents with different patterns of enzyme elevation 2
Monitoring and Management Recommendations
When to Hold Fenofibrate
- Discontinue fenofibrate if signs or symptoms of liver injury develop 1
- Discontinue fenofibrate if elevated enzyme levels persist (ALT or AST >3 times ULN) 1
- Discontinue immediately if transaminase elevations are accompanied by elevation of bilirubin 1
- Do not restart fenofibrate in these patients if there is no alternative explanation for the liver injury 1
Monitoring Protocol
- Monitor liver function tests at baseline before initiating fenofibrate therapy 1
- Continue monitoring periodically for the duration of therapy 1
- Be alert for symptoms of hepatotoxicity including dark urine, abnormal stool, jaundice, malaise, abdominal pain, and nausea 1
- Patients with jaundice or abnormal laboratory tests during fenofibrate therapy should have the medication promptly discontinued 2
Risk Factors for Fenofibrate-Induced Liver Injury
- Higher BMI, elevated baseline triglycerides, and elevated baseline ALP and gamma-GTP levels have been associated with increased risk of liver function test abnormalities during fenofibrate therapy 3
- Delayed discontinuation of fenofibrate after signs of liver injury appear is associated with worse outcomes, including progression to liver transplantation or death 2
Special Considerations
- Fenofibrate is contraindicated in patients with active liver disease, including those with primary biliary cirrhosis and unexplained persistent liver function abnormalities 1
- When considering statin-fibrate combination therapy, fenofibrate is preferred over gemfibrozil due to lower risk of adverse effects 4
- However, combination therapy with statins and fibrates has not been shown to improve atherosclerotic cardiovascular disease outcomes and is generally not recommended 4
Clinical Perspective
- While most cases of fenofibrate-induced liver injury are self-limited after drug discontinuation, severe injury can occur if the drug is not promptly withdrawn 2
- Liver injury patterns from fenofibrate can be hepatocellular, chronic active, and cholestatic hepatitis, and cirrhosis has occurred in association with chronic active hepatitis 1
- Fenofibrate-induced liver injury can occur rapidly, with some cases developing within 48 hours after the first dose 5
By promptly recognizing and addressing transaminitis in patients taking fenofibrate, clinicians can prevent progression to more severe liver injury and potentially life-threatening complications.