From the Guidelines
Fenofibrate can cause significant side effects, including muscle pain, digestive issues, and increased risk of rhabdomyolysis, especially when combined with statins, and patients should be closely monitored for these adverse effects. The most common side effects of fenofibrate include:
- Digestive issues like nausea, stomach pain, and diarrhea
- Muscle pain, which can rarely progress to rhabdomyolysis, a serious condition that can lead to kidney failure 1
- Headaches, dizziness, or mild skin rashes
- Laboratory abnormalities, such as elevated liver enzymes and increased homocysteine levels Less common but serious side effects of fenofibrate include:
- Gallstones
- Pancreatitis
- Allergic reactions It is essential to note that fenofibrate can interact with other medications, particularly statins, increasing the risk of muscle problems 1. Additionally, kidney function may worsen in some patients, especially those with pre-existing kidney disease, and fenofibrate is contraindicated in individuals with an estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m2 2, 3. Regular blood tests are crucial to monitor liver function, kidney function, and muscle enzymes in patients taking fenofibrate, and healthcare providers should be contacted immediately if severe muscle pain, yellowing of skin or eyes, dark urine, or signs of allergic reaction occur.
From the FDA Drug Label
5. 4 Serum Creatinine Elevations in serum creatinine have been reported in patients on fenofibrate.
- 5 Cholelithiasis Fenofibrate, like clofibrate and gemfibrozil, may increase cholesterol excretion into the bile, leading to cholelithiasis.
- 7 Pancreatitis Pancreatitis has been reported in patients taking fenofibrate, gemfibrozil and clofibrate.
- 8 Hematologic Changes Mild to moderate hemoglobin, hematocrit, and white blood cell decreases have been observed in patients following initiation of fenofibrate therapy.
- 9 Hypersensitivity Reactions Acute Hypersensitivity Anaphylaxis and angioedema have been reported post-marketing with fenofibrate.
- 10 Venothromboembolic Disease In the FIELD trial, pulmonary embolus (PE) and deep vein thrombosis (DVT) were observed at higher rates in the fenofibrate- than the placebo-treated group.
- 11 Paradoxical Decreases in HDL Cholesterol Levels There have been post-marketing and clinical trial reports of severe decreases in HDL cholesterol levels (as low as 2 mg/dL) occurring in diabetic and non-diabetic patients initiated on fibrate therapy.
The side effects of fenofibrate include:
- Elevations in serum creatinine
- Cholelithiasis due to increased cholesterol excretion into the bile
- Pancreatitis
- Hematologic changes, such as mild to moderate decreases in hemoglobin, hematocrit, and white blood cell counts
- Hypersensitivity reactions, including anaphylaxis and angioedema
- Venothromboembolic disease, including pulmonary embolus and deep vein thrombosis
- Paradoxical decreases in HDL cholesterol levels 4
From the Research
Side Effects of Fenofibrate
The side effects of fenofibrate can be categorized into several groups, including:
- Gastrointestinal disturbances, such as abdominal discomfort, diarrhea, and constipation, which occur in approximately 5% of patients 5, 6
- Neurologic effects, including fatigue, headache, loss of libido, impotence, dizziness, and insomnia, with a total incidence of 3 to 4% 6
- Muscle tenderness, often accompanied by elevated creatine phosphokinase levels, occurring in about 1% of patients 6
- Skin rash, which develops in approximately 2% of patients, an incidence that appears significantly higher than that of placebo control groups 6
- Transient elevations in transaminase and creatine phosphokinase levels, which commonly occur 5
- Isolated cases of hepatitis with substantially elevated transaminase levels have been reported 5
Less Common Side Effects
Less common side effects of fenofibrate include:
- Hepatic effects, such as hepatomegaly, peroxisome proliferation, and hepatic carcinomas, which have been observed in rodents but not in humans 5, 7
- Renal effects, which have been reported in dogs but not in humans 7
- Gallstones, which have not been shown to have increased incidence in treated patients despite an increased biliary lithogenic index 5, 7, 6
- Weight loss, sexual asthenia, and hematologic effects, which have been reported in postmarketing experiences 7
Rare but Clinically Relevant Side Effects
Rare but clinically relevant side effects of fenofibrate include:
- Fibrate-associated adverse effects beyond muscle and liver toxicity, which have been reviewed in the literature 8
- Protective effects against liver steatosis, including enhanced expression of genes promoting hepatic fatty acid β-oxidation, reduced hepatic insulin resistance, and inhibition of inflammatory mediators 9