What are fibrates?
Fibrates, also known as fibric acid derivatives, are a class of oral medications primarily used to treat hypertriglyceridemia, a condition characterized by high levels of triglycerides in the blood. While their main effect is lowering triglycerides, they also have a beneficial impact on other blood lipids. Specifically, fibrates can raise high-density lipoprotein (HDL) cholesterol, often called "good cholesterol," and can have a variable effect on low-density lipoprotein (LDL) cholesterol, depending on the drug. They are generally used in conjunction with lifestyle changes, such as a heart-healthy diet and regular exercise, and may be prescribed alone or in combination with other lipid-lowering agents like statins.
Which drug is considered a fibrate?
The most commonly prescribed fibrate drugs in clinical practice include:
- Fenofibrate: Available under brand names such as Tricor, Antara, Fenoglide, and Lipofen, this is a widely used fibrate. Fenofibrate is a prodrug that is converted into its active form, fenofibric acid, within the body. Fenofibrate and fenofibric acid are used to treat severe hypertriglyceridemia and primary hypercholesterolemia or mixed dyslipidemia. Different formulations are not bioequivalent and may have different requirements regarding food intake.
- Gemfibrozil: Sold under the brand name Lopid, gemfibrozil is another common fibrate. It is particularly effective for treating very high triglycerides that increase the risk of pancreatitis. Unlike fenofibrate, gemfibrozil is known to have significant interactions with certain statins. It is typically taken twice a day, 30 minutes before the morning and evening meals.
- Bezafibrate: A fibrate used in various countries, though it is not approved for clinical use in the United States. It is used to lower high triglycerides and LDL cholesterol while increasing HDL.
- Ciprofibrate: Another fibric acid derivative used primarily for treating hyperlipoproteinemia in other regions of the world.
- Fenofibric Acid: The active metabolite of fenofibrate, which is also available as a direct medication under brand names such as Trilipix and Fibricor.
How fibrates work
Fibrates exert their effects by activating peroxisome proliferator-activated receptor alpha (PPAR-alpha), a nuclear transcription receptor. Activation of PPAR-alpha leads to several changes in lipid metabolism:
- Increased Lipoprotein Lipase Activity: Fibrates increase the expression and activity of lipoprotein lipase (LPL) in muscle and adipose tissue. LPL is an enzyme that helps break down triglycerides, leading to their increased removal from the bloodstream.
- Reduced Very Low-Density Lipoprotein (VLDL) Production: Fibrates decrease the liver's secretion of VLDL particles, which are the primary carriers of triglycerides in the body.
- Modified Apolipoprotein Levels: Fibrates transcriptionally up-regulate apolipoproteins A-I and A-II, which are major components of HDL cholesterol. This leads to an increase in HDL levels. They also down-regulate apolipoprotein C-III, an inhibitor of lipolysis.
Uses and indications
Fibrates are an important therapeutic option for managing lipid disorders, especially those involving elevated triglycerides. Their main indications include:
- Severe Hypertriglyceridemia: Fibrates are particularly effective for patients with very high triglyceride levels (often > 500 mg/dL), which pose a significant risk for acute pancreatitis.
- Mixed Dyslipidemia: For patients with both elevated triglycerides and high cholesterol, fibrates can be used to improve the overall lipid profile.
- Diabetic Retinopathy: Some studies, such as the FIELD and ACCORD-Eye trials, have shown that fenofibrate may slow the progression of diabetic retinopathy in patients with type 2 diabetes.
- Metabolic Syndrome: Fibrates are often considered for patients with metabolic syndrome, who typically have a combination of high triglycerides and low HDL.
Comparison of key fibrates
While fenofibrate and gemfibrozil are both effective fibrates, they have notable differences that influence a physician's choice of treatment.
| Feature | Fenofibrate | Gemfibrozil |
|---|---|---|
| Dosing Frequency | Typically once daily | Usually twice daily, before meals |
| Statin Interaction | Lower risk of muscle issues when combined with statins; often the safer choice for combination therapy | Higher risk of myopathy/rhabdomyolysis when combined with statins like simvastatin and lovastatin; combination is generally avoided |
| LDL Effect | May modestly reduce LDL cholesterol | Neutral or potentially slightly increased LDL effect |
| Specific Use Case | Suitable for a wider range of dyslipidemias; may decrease small, dense LDL particles | Often chosen specifically for very high triglycerides to reduce pancreatitis risk |
| Bioavailability | Varies among different formulations (e.g., micronized, nanocrystal); some require food | Absorption occurs from the GI tract; taken before meals |
Side effects and risks
Like all medications, fibrates are associated with a range of potential side effects. Most are mild, but more serious complications can occur:
Common side effects:
- Gastrointestinal disturbances, such as nausea, diarrhea, and stomach pain.
- Headache.
- Back pain.
Serious side effects:
- Myopathy and Rhabdomyolysis: Fibrates, especially when combined with statins, can increase the risk of muscle pain, tenderness, weakness, and severe muscle breakdown (rhabdomyolysis). This risk is particularly high with gemfibrozil and certain statins.
- Liver Problems: Fibrates can cause mild, reversible elevations in liver enzymes. In rare cases, more severe liver injury has been reported, necessitating monitoring of liver function tests.
- Gallstones (Cholelithiasis): By increasing the amount of cholesterol in bile, fibrates can increase the risk of developing gallstones.
- Kidney Issues: Fibrates can cause a mild increase in serum creatinine levels, and caution is needed in patients with existing renal impairment.
Drug interactions and contraindications
Patients should be aware of potential drug interactions and contraindications before starting fibrate therapy:
- Statins: As mentioned, the combination of fibrates and statins, particularly gemfibrozil with simvastatin or lovastatin, significantly increases the risk of muscle toxicity and is often avoided.
- Warfarin: Fibrates can increase the blood-thinning effect of warfarin. The dose of warfarin may need to be adjusted, and blood levels monitored closely.
- Immunosuppressants: Coadministration with immunosuppressants like ciclosporin or tacrolimus can increase the risk of kidney dysfunction.
- Contraindications: Fibrates are not suitable for all patients. They are contraindicated in individuals with severe liver disease, severe kidney disease, or pre-existing gallbladder disease. They are also not recommended for pregnant or breastfeeding women.
Conclusion
In summary, fibrates represent a crucial class of medications, with fenofibrate and gemfibrozil being the most prominent examples, used to effectively manage high triglyceride levels and improve other lipid markers. By activating the PPAR-alpha receptor, these drugs alter lipid metabolism to reduce triglycerides and increase HDL cholesterol. The specific choice of a fibrate, such as fenofibrate or gemfibrozil, often depends on the patient's individual lipid profile and concomitant medications, particularly the need to co-administer with a statin. While generally safe and effective, fibrates carry important considerations regarding side effects, drug interactions, and contraindications. Regular monitoring by a healthcare provider is essential to ensure both safety and optimal treatment outcomes for patients.
For more detailed prescribing information and brand names, patients and healthcare professionals can refer to resources like the MedlinePlus drug information page for fenofibrate or other authoritative sources.
