Fenofibrate is FDA-approved for treating patients with hypertriglyceridemia, primary hypercholesterolemia, or mixed dyslipidemia. It works by lowering levels of low-density lipoprotein (LDL) cholesterol, total cholesterol, triglycerides, and apolipoprotein B, while increasing high-density lipoprotein (HDL) cholesterol in adults. The medication should be used alongside dietary restrictions on cholesterol and fat, as well as exercise, when diet and lifestyle changes alone have not been sufficient.
BRAND NAMES
Tricor: Tricor is available in doses of 48 mg and 145 mg and is used to treat high cholesterol, elevated triglycerides, and mixed dyslipidemia.
Lipofen: Lipofen comes in a 150 mg dose and is prescribed for managing high cholesterol and triglycerides.
Antara: Antara is available in 43 mg and 130 mg doses and is used to treat high triglycerides and mixed dyslipidemia.
Fenoglide: Fenoglide is available in 40 mg and 120 mg doses and is prescribed for high cholesterol and triglycerides.
MECHANISM OF ACTION
Fibrates, like fenofibrate, activate peroxisome proliferator-activated receptors alpha (PPAR-alpha), which increase the activity of lipoprotein lipase, stimulate HDL synthesis, and reduce liver production of apolipoprotein C. This results in improved clearance of triglyceride-rich particles and enhanced plasma breakdown. Fibrates also promote fatty acid oxidation through acyl CoA synthetase and other enzymes, which further decreases triglyceride production. As a result, plasma triglyceride and very low-density lipoprotein (VLDL) levels decrease, with triglyceride levels potentially dropping by 30% to 60%. Additionally, fenofibrate may promote increased uric acid excretion and reduce fibrinogen levels, offering potential benefits for patients with gout and thrombosis.
PHARMACOKINETICS
Absorption:
Fenofibrate is efficiently absorbed from the gastrointestinal tract, reaching peak plasma concentrations within 4 to 6 hours after oral administration.
Distribution:
Fenofibrate is highly bound to plasma proteins, primarily albumin, with binding rates of 99% to 99.5%.
Metabolism:
Fenofibrate is converted in the liver to its active form, fenofibric acid, primarily through CYP3A4 enzymes.
Elimination:
The half-life of fenofibrate is around 20 hours, while the half-life of fenofibric acid is also approximately 20 hours. Both fenofibrate and its metabolites are mainly eliminated through the kidneys, with a small portion excreted in feces. About 60-80% of the drug is excreted in urine, mostly as metabolites, with less than 1% eliminated unchanged. The rest is excreted via bile.
PHARMACOGYNAMICS
Fenofibrate activates PPAR-α, leading to increased lipoprotein lipase activity and decreased apolipoprotein C-III, which enhances triglyceride clearance. It reduces triglycerides (30–60%), lowers LDL and VLDL, and increases HDL (10–30%). It also improves the lipid profile, lowers fibrinogen, and may increase uric acid excretion, helping in conditions like thrombosis and gout
DOSAGE AND ADMINISTRATION
Fenofibrate capsules and tablets are consumed orally once daily, with or without food. Capsules should be swallowed whole, not crushed, chewed, or dissolved. Fenofibrate can be explored for patients using moderate-intensity statins if the possible advantages, such as lower cardiovascular risk, outweigh the risk of side effects. Dosage modifications are usually given every 4 to 8 weeks, depending on patient response. Different fenofibrate formulations are not bioequivalent, so switching between formulations should be done carefully.
Available Forms:
- Capsules: 30–200 mg
- Delayed-release (choline fenofibrate): 45 mg, 135 mg
- Fenofibric acid tablets: 35 mg, 105 mg
- Fenofibrate tablets: 40–160 mg
Adult Tablet Doses:
- Hypertriglyceridemia: 54–160 mg daily
- Hypercholesterolemia / Mixed dyslipidemia: 160 mg daily
CONTRAINDICATION
- Severe renal impairment
- Active liver disease or unexplained liver enzyme elevations
- Gallbladder disease (risk of gallstones)
- Known hypersensitivity to fenofibrate
- Breastfeeding (risk to infant)
- Children under 18 years (safety not established)
DRUG INTERACTION
- Statins: Increased risk of myopathy and rhabdomyolysis.
- Anticoagulants (Warfarin): Increased risk of bleeding; monitor INR.
- Cyclosporine: Increased risk of renal toxicity.
- Bile acid sequestrants (Cholestyramine): Reduce fenofibrate absorption; take 1 hour before or 4-6 hours after.
- Renal-affecting drugs: Increased risk of toxicity.
- Other lipid-lowering drugs: Increased risk of muscle side effects.
- Anti-diabetic drugs: May increase risk of hypoglycemia; monitor glucose.
SIDE EFFECTS
Common Side Effects
- GI issues (nausea, abdominal pain, diarrhea)
- Muscle pain, weakness, cramping
- Elevated liver enzymes
- Rash, itching
- Gallstones (abdominal discomfort)
- Increased creatinine, kidney issues
- Headache, dizziness
Serious Side Effects:
- Rhabdomyolysis (severe muscle pain, dark urine)
- Liver toxicity (jaundice, pain)
- Allergic reactions (swelling, difficulty breathing)
TOXICITY
- Muscle: Pain, weakness, dark urine (with statins or renal issues).
- Liver: Jaundice, nausea, abdominal pain (monitor liver enzymes).
- Kidney: Elevated creatinine, reduced urine (monitor function).
- Gallbladder: Pain, nausea (risk of gallstones).
- Allergic: Rash, swelling, difficulty breathing (rare).
