What are the side effects of fenofibrate (Fibric acid derivative)?

From the Guidelines

Fenofibrate commonly causes side effects including digestive issues like nausea, stomach pain, and diarrhea, and muscle pain, which rarely can progress to a serious condition called rhabdomyolysis, as reported in various studies 1.

Side Effects of Fenofibrate

The medication can cause a range of side effects, including:

• Digestive issues like nausea, stomach pain, and diarrhea
• Muscle pain, which can rarely progress to rhabdomyolysis
• Headaches, dizziness, and mild skin reactions
• Effects on liver function, potentially raising liver enzymes
• Increased cholesterol in the gallbladder, raising the risk of gallstones
• Less common but serious side effects include severe allergic reactions, unexplained bleeding or bruising, and respiratory symptoms

Mechanism and Interactions

These side effects occur because fenofibrate works by activating peroxisome proliferator-activated receptors (PPARs) to reduce triglycerides and increase HDL cholesterol, but this mechanism can affect multiple body systems. The medication can also interact with other drugs, particularly statins, increasing the risk of muscle problems, as noted in studies such as the FIELD study 1.

Monitoring and Precautions

Patients should report severe muscle pain, yellowing of skin/eyes, dark urine, or unusual fatigue to their healthcare provider immediately, as these may indicate serious complications requiring medical attention. Renal status should be evaluated before fenofibrate initiation, within 3 months after initiation, and every 6 months thereafter, as recommended in guidelines 1. Fenofibrate should not be used if moderate or severe renal impairment is present, and the dose should not exceed 54 mg/day if the eGFR is between 30 and 59 mL/min per 1.73 m2 1.

From the FDA Drug Label

Patients should also be advised to inform their physicians of symptoms of liver injury (e.g., jaundice, abnormal pain, nausea, malaise, dark urine, abnormal stool, pruritus); any muscle pain, tenderness, or weakness; onset of abdominal pain; or any other new symptoms. Call your doctor for medical advice about side effects.

The side effects of fenofibrate include:

• Liver injury (e.g., jaundice, abnormal pain, nausea, malaise, dark urine, abnormal stool, pruritus)
• Muscle pain, tenderness, or weakness
• Onset of abdominal pain
• Other new symptoms 2 2

From the Research

Fenofibrate Side Effects

• The most common side effects of fenofibrate include gastrointestinal effects, muscle pain, skin problems, and sweating or dizziness, as reported in a study of 7,145 patients in European clinical trials 3.
• Other side effects that occurred more commonly in fenofibrate patients versus placebo include skin reactions, neurologic effects, and musculoskeletal reactions 3.
• Laboratory tests have shown mildly abnormal results for liver function, leukocytes, and hemoglobin, although these reactions were significant enough to be considered adverse drug experiences only occasionally 3.
• Hepatobiliary tests have shown an increase in cholesterol saturation, but gallstones have seldom been associated with fenofibrate 3.
• Postmarketing reports have noted hepatic, renal, gallstones, cutaneous, hematologic, sexual asthenia, and weight loss as potential side effects, although the rate of reactions has been low (about 115/year or a 0.3% incidence rate) 3.

Liver Injury

• Fenofibrate has been associated with rare instances of hepatotoxicity, including mild aminotransferase elevations and severe chronic injury such as fibrosis or cirrhosis, resulting in liver transplantation or death 4, 5.
• The latency of disease has been reported to range between weeks to years, and jaundice or abnormal laboratory tests during fenofibrate therapy should trigger prompt discontinuation 4, 5.
• A case report described a 63-year-old male who developed symptoms of fatigue and anorexia 48 hours after taking fenofibrate for the first time, with aminotransferase levels more than 10 times the upper limit of normal 4.
• Another study described 7 cases of acute liver injury associated with fenofibrate, with diverse injury patterns and variable latency, and highlighted the importance of routine liver biochemistry monitoring 5.

Other Effects

• Fenofibrate has been shown to improve liver function and reduce the toxicity of the bile acid pool in patients with primary biliary cholangitis and primary sclerosing cholangitis who are partial responders to ursodiol 6.
• The addition of prescription omega-3 fatty acids to fenofibrate therapy has been shown to result in a statistically significant reduction in triglyceride levels in subjects with very high triglyceride levels 7.