What it's for (Indications)
- Fenofibrate, a fibric acid derivative, is indicated as adjunctive therapy to diet for the treatment of various dyslipidemias to improve lipid profiles and reduce associated risks.
- Its primary indications include severe hypertriglyceridemia (Type IV and V hyperlipidemias) in adults, where it is used to reduce the risk of pancreatitis.
- Additionally, it is indicated for the treatment of primary hypercholesterolemia or mixed dyslipidemia (Type IIa and IIb hyperlipidemias) in adults, as an adjunct to diet, to reduce elevated LDL-cholesterol (LDL-C), total cholesterol (total-C), triglycerides, and apolipoprotein B (Apo B), and to increase high-density lipoprotein cholesterol (HDL-C).
- Treatment should be initiated only after adequate trial of diet and other non-pharmacological measures, and patients should be routinely monitored for lipid levels to ensure therapeutic efficacy and safety.
- The decision to use fenofibrate should be based on a comprehensive assessment of cardiovascular risk factors.
Dosage Information
| Type | Guideline |
|---|---|
| Standard | The dosage of fenofibrate varies depending on the specific formulation (e.g., micronized, non-micronized, delayed-release) and the patient's individual lipid profile and renal function. For adults, typical dosages range from 48 mg to 200 mg orally once daily, often taken with meals to optimize absorption and bioavailability. For example, fenofibrate (micronized) capsules may be prescribed at 67 mg, 134 mg, or 200 mg daily, while fenofibrate (non-micronized) tablets might be 48 mg or 145 mg daily. In patients with mild to moderate renal impairment (eGFR 30-80 mL/min/1.73m²), the dosage should be reduced, typically starting with a lower dose such as 48 mg or 54 mg once daily, and adjusted cautiously based on lipid response and renal function monitoring. Fenofibrate is contraindicated in patients with severe renal impairment (eGFR <30 mL/min/1.73m²). Regular monitoring of lipid levels, liver function tests, and renal function is essential to guide dosage adjustments and assess therapeutic response and safety. |
Safety & Warnings
Common Side Effects
- Fenofibrate is generally well-tolerated, but like all medications, it can cause various side effects, ranging from mild to serious.
- Common side effects include headache, abdominal pain, nausea, constipation, diarrhea, and dyspepsia.
- Clinically significant laboratory abnormalities frequently observed are transient elevations in liver transaminases (ALT, AST), which typically normalize with continued treatment or dose reduction, and increases in serum creatinine.
- Less common but more serious adverse events include cholelithiasis (gallstones), which may necessitate cholecystectomy, and pancreatitis.
- Myopathy, including rhabdomyolysis, can occur, particularly when fenofibrate is co-administered with statins or in patients with predisposing factors such as renal impairment or hypothyroidism.
- Other reported side effects include venous thromboembolism (VTE), pulmonary embolism, hepatitis, anemia, leukopenia, and rare but severe dermatological reactions like Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN).
- Patients should be advised to report any unexplained muscle pain, tenderness, or weakness, dark urine, or signs of liver injury (e.
- g.
- , jaundice, dark urine, severe abdominal pain) promptly to their healthcare provider.
Serious Warnings
- Black Box Warning: Fenofibrate does not carry a formal FDA-mandated Black Box Warning. However, healthcare professionals and patients must be aware of several **Serious Warnings** associated with its use, which necessitate careful monitoring and patient education. These include a significant risk of **Hepatotoxicity**, manifested by persistent elevations in liver transaminases (ALT or AST), which can sometimes be severe and require discontinuation of the drug. Regular monitoring of liver function tests is crucial. There is also a notable risk of **Myopathy and Rhabdomyolysis**, especially when fenofibrate is co-administered with statins or in patients with predisposing factors such as advanced age, renal insufficiency, or hypothyroidism. Patients must be counseled to report any unexplained muscle pain, tenderness, or weakness immediately. Furthermore, fenofibrate can lead to **Cholelithiasis** (gallstone formation), as it increases cholesterol excretion into bile, potentially necessitating surgical intervention. Patients with pre-existing gallbladder disease are particularly at risk. Although used to reduce pancreatitis risk in severe hypertriglyceridemia, fenofibrate itself has been associated with cases of **Pancreatitis**. These serious adverse events, while not formally boxed, represent critical safety concerns that warrant thorough patient assessment, continuous monitoring, and prompt intervention if symptoms arise, given their potential for severe morbidity.
- Several critical warnings and precautions are associated with fenofibrate therapy.
- **Hepatotoxicity** is a significant concern; persistent elevations in serum transaminases (ALT or AST >3 times the upper limit of normal) necessitate discontinuation.
- Liver function tests should be monitored periodically.
- **Myopathy and Rhabdomyolysis** risk is increased with fenofibrate, especially when co-administered with HMG-CoA reductase inhibitors (statins), in elderly patients, those with renal impairment, or pre-existing hypothyroidism.
- Patients should be advised to report any unexplained muscle pain, tenderness, or weakness.
- **Cholelithiasis** (gallstone formation) can occur due to increased cholesterol excretion into the bile; fenofibrate is contraindicated in patients with pre-existing gallbladder disease.
- **Pancreatitis** has been reported, sometimes secondary to hypertriglyceridemia not adequately controlled by the drug or due to biliary tract obstruction.
- **Renal Impairment** requires dose reduction, and fenofibrate is contraindicated in severe renal dysfunction.
- Reversible increases in serum creatinine are common and usually non-progressive.
- **Hematologic changes**, such as mild decreases in hemoglobin, hematocrit, and white blood cell count, have been observed.
- **Venous Thromboembolism (VTE)**, including pulmonary embolism, has been noted in clinical trials, warranting careful consideration in patients at risk.
- Additionally, severe hypersensitivity reactions, including dermatologic manifestations, have been reported.
How it Works (Mechanism of Action)
Fenofibrate is a prodrug that is rapidly hydrolyzed by esterases to its active metabolite, fenofibric acid. Fenofibric acid exerts its lipid-modifying effects primarily through activation of peroxisome proliferator-activated receptor alpha (PPARα). PPARα is a nuclear receptor that regulates the transcription of genes involved in lipid metabolism. Activation of PPARα by fenofibric acid leads to several key changes in lipoprotein synthesis and catabolism: it increases the synthesis of lipoprotein lipase (LPL), an enzyme crucial for the breakdown of triglyceride-rich lipoproteins (VLDL and chylomicrons); it reduces the hepatic synthesis of very low-density lipoprotein (VLDL) and apolipoprotein C-III (Apo C-III), an inhibitor of LPL; and it increases the synthesis of apolipoprotein A-I (Apo A-I) and apolipoprotein A-II (Apo A-II), which are major components of high-density lipoprotein (HDL). These combined actions result in a significant reduction in plasma triglycerides and moderate reductions in LDL-C and total-C, while simultaneously increasing HDL-C levels, thereby improving the overall atherogenic lipid profile.
Commercial Brands (Alternatives)
No other brands found for this formula.