From the Guidelines
Fibrates should be initiated in patients with severe hypertriglyceridemia (triglyceride levels ≥500 mg/dL) to reduce the risk of acute pancreatitis, as recommended by the most recent guidelines 1. When considering the initiation of fibrates, it is essential to evaluate the patient's triglyceride levels and assess for secondary causes of hypertriglyceridemia.
- Fibrates may also be considered as second-line therapy in patients with moderate hypertriglyceridemia (150-499 mg/dL) who have failed lifestyle modifications and statin therapy, particularly in those with low HDL cholesterol levels or metabolic syndrome.
- Common fibrates include fenofibrate (typically 145 mg daily), gemfibrozil (600 mg twice daily), and bezafibrate (400 mg daily).
- Before starting fibrates, baseline liver function tests and creatinine levels should be checked, as these medications can cause hepatotoxicity and may worsen renal function, as noted in previous guidelines 1.
- Fibrates should be used cautiously with statins, especially gemfibrozil with statins, due to increased risk of myopathy, as highlighted in earlier studies 1.
- They work by activating peroxisome proliferator-activated receptor alpha (PPAR-α), which increases lipoprotein lipase activity and reduces apolipoprotein C-III production, thereby enhancing triglyceride clearance from the bloodstream.
- Regular monitoring of liver function, renal function, and muscle symptoms is necessary during treatment, as emphasized in the guidelines 1.
From the FDA Drug Label
Patients should be placed on an appropriate lipid-lowering diet before receiving fenofibrate tablets and should continue this diet during treatment with fenofibrate tablets. Excess body weight and excess alcoholic intake may be important factors in hypertriglyceridemia and should be addressed prior to any drug therapy. Diseases contributory to hyperlipidemia, such as hypothyroidism or diabetes mellitus should be looked for and adequately treated. The initial dose of fenofibrate tablet is 160 mg once daily. Dosage should be individualized according to patient response and should be adjusted if necessary following repeat lipid determinations at 4 to 8 week intervals.
Initiation of Fibrates: Fibrates, such as fenofibrate, should be initiated after:
- Patients have been placed on an appropriate lipid-lowering diet
- Excess body weight and excess alcoholic intake have been addressed
- Diseases contributory to hyperlipidemia, such as hypothyroidism or diabetes mellitus, have been looked for and adequately treated The initial dose of fenofibrate is 160 mg once daily for primary hypercholesterolemia or mixed dyslipidemia, and 54 mg per day to 160 mg per day for severe hypertriglyceridemia, with dosage individualized according to patient response 2.
From the Research
Initiation of Fibrates
Fibrates are a class of lipid-lowering medication primarily used as second-line agents behind statins 3. The decision to initiate fibrates depends on various factors, including the patient's lipid profile, cardiovascular risk, and response to initial therapy.
Indications for Fibrates
- Severe hypertriglyceridemia (≥5.6 mmol/L [≥500 mg/dL]) requires immediate use of triglyceride-lowering agents, including fibrates 4
- Mild to moderate hypertriglyceridemia (1.7-5.6 mmol/L [150-499 mg/dL]) may require additional therapy with fibrates if statin therapy is insufficient 4
- Patients with metabolic syndrome and elevated triglyceride levels may benefit from fenofibrate treatment 5
Combination Therapy
- Fibrates can be used in combination with statins, but this should be done with caution and under close monitoring due to the increased risk of rhabdomyolysis 6
- Combination therapy with fibrates and omega-3 fatty acids may be effective in reducing triglyceride levels 7
Patient Selection
- Patients with normal renal, liver, and thyroid function tests are suitable candidates for fibrate therapy 6
- Patients with high-risk profiles, such as those with mixed hyperlipidemia, may benefit from combination therapy with fibrates and statins 6