fenofibrate

Action and Spectrum

Actions and Spectrum: 

The action of fenofibrate includes: 

• Lowering triglycerides: fenofibrate reduces the levels of triglycerides in the blood by decreasing their production in the liver. 
• Raising HDL cholesterol: fenofibrate also increases the levels of HDL cholesterol in the blood, which is also known as “good cholesterol.” This is because it enhances the transport of cholesterol from outer tissues to the liver for elimination. 
• Modifying LDL cholesterol: fenofibrate may modify the LDL cholesterol (also known as “bad cholesterol”) particles to make them less harmful and less likely to cause plaque buildup in the arteries. 

The spectrum of fenofibrate includes: 

• Hypertriglyceridemia: fenofibrate is primarily used to treat increase levels of triglyceride fats in the blood, which can increase the risk of heart disease. 
• Low HDL cholesterol: fenofibrate is also used to increase the levels of HDL cholesterol in the blood, which can decrease the risk of heart disease. 
• Metabolic syndrome: fenofibrate may be used to treat metabolic syndrome, a condition characterized by a combination of high blood pressure, high blood sugar, excess body fat, and abnormal cholesterol levels. 
• Diabetes: fenofibrate may be used to treat certain complications of diabetes, such as diabetic retinopathy, a condition that can cause vision loss. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Increased LFT’s (3-13%) 

1-10% 

Rhinitis (2%) 

Back pain (3%) 

CPK increased (3%) 

Abdominal pain (5%) 

Headache (3%) 

Respiratory disorder (6%) 

Constipation (2%) 

Nausea (2%) 

Postmarketing Reports 

Anemia 

Myopathies 

Peptic ulcer 

Dysrhythmias 

Leukopenia 

Peripheral vascular disease 

Rash 

Muscle pain 

Pancreatitis 

Myositis 

Cholelithiasis 

CNS depression 

Diarrhea 

Flatulence 

Pulmonary embolus 

Renal damage 

Black Box Warning

Black Box Warning: 

The black box warning for fenofibrate relates to its potential to cause serious muscle-related side effects, including rhabdomyolysis. Rhabdomyolysis is a rare but serious situation in which muscle tissue breaks down leads to release the muscle fibers into the bloodstream. These muscle fibers can then damage the kidneys and lead to kidney failure. 

The black box warning for fenofibrate states that it should not be used in combination with certain other medications that can increase the risk of muscle-related side effects, such as statins. Statins belongs to class of drugs used to lower cholesterol levels, and when combined with fenofibrate, the risk of muscle-related side effects may increase. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

• Gallbladder disease: fenofibrate may increase the risk of gallbladder disease, particularly in women. 
• Pancreatitis: fenofibrate may increase the risk of pancreatitis. 
• Severe hypertriglyceridemia: fenofibrate is not recommended for patients with severe hypertriglyceridemia, defined as triglyceride levels greater than 1000 mg/dL. 
• Breastfeeding: fenofibrate is not recommended for breastfeeding women, as it may pass into breast milk and cause harm to the nursing infant. 
• Pregnancy: fenofibrate is classified as Pregnancy Category C, which means that it should be used with caution during pregnancy only if the potential benefits outweigh the potential risks to the fetus. 

Caution 

• Renal impairment: fenofibrate is primarily excreted by the kidneys, so it should be used with caution in patients with renal impairment. Dosage adjustments may be necessary to prevent accumulation of the drug. 
• Hepatic impairment: fenofibrate is metabolized by the liver, so it should also be used with caution in patients with hepatic impairment. Dosage adjustments may be necessary to prevent accumulation of the drug. 
• Muscle-related side effects: fenofibrate can increase the risk of muscle-related side effects, including myopathy and rhabdomyolysis. Patients should be monitored for signs of muscle pain, weakness, and tenderness, particularly during the first few months of treatment. 
• Gallbladder disease: fenofibrate may increase the risk of gallbladder disease, particularly in women. Patients with a history of gallbladder disease should be monitored closely while taking fenofibrate. 
• Pancreatitis: fenofibrate may increase the risk of pancreatitis. 
• Hypersensitivity reactions: fenofibrate can cause hypersensitivity reactions, including rash, itching, and anaphylaxis. Patients with a history of hypersensitivity to fenofibrate or any of its components should not take this medication. 
• Interaction with other medications: fenofibrate can interact with other medications, including statins and anticoagulants. Patients should inform their physician of all medications they are taking before starting treatment with fenofibrate. 
• Pregnancy and breastfeeding: fenofibrate should be used with caution during pregnancy and is not recommended for breastfeeding women, as it may pass into breast milk and cause harm to the nursing infant. 

Pregnancy / Lactation

Pregnancy consideration:  

AU TGA pregnancy category: B3
US FDA pregnancy category: Not assigned. 

Lactation:   

Excreted into human milk is Not known.  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies do not show risk to the fetus in the first/later trimester.        
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women        
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.       
• Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.        
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.        
• Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

fenofibrate is a medication used to treat increase levels of cholesterol and triglyceride fats in the blood. It belongs to fibrates class of drugs and works by activating peroxisome proliferator-activated receptor alpha (PPAR-alpha), a nuclear receptor involved in lipid metabolism. 

When fenofibrate activates PPAR-alpha, it increases the expression of genes involved in fatty acid oxidation, leading to a decrease in circulating triglyceride levels and an rise in high-density lipoprotein (HDL) cholesterol levels.

Additionally, fenofibrate also reduces the production of very low-density lipoprotein (VLDL) cholesterol, which is the precursor to LDL cholesterol. 

Pharmacodynamics: 

Mechanism of action: Enhancement of lipoprotein lipase synthesis by increasing VLDL catabolism, fatty acid oxidation, and elimination of triglyceride-rich particles results in a reduction of 30-60% in total plasma triglycerides; although in some hypertriglyceridemic patients, HDL may only increase slightly. 

Pharmacokinetics: 

Absorption 

The bioavailability of this substance is between 60-90%. Its onset takes approximately 2 weeks, and it reaches peak plasma concentration between 2-8 hours after administration. 

Distribution 

This substance has a wide distribution throughout most tissues in the body, and it is highly protein-bound, with approximately 99% bound to proteins. 

Metabolism 

When metabolized in the liver, this substance produces two primary metabolites: fenofibric acid, which is the active metabolite, and fenofibric acid glucuronide, whose activity is currently unknown. 

Elimination and Excretion 

The half-life of this substance ranges from 10-35 hours, with an average of 20 hours. It is not dialyzable by hemodialysis. The primary routes of excretion are through the urine, accounting for 60-93% of elimination, and through the feces, accounting for 5-25%. 

Adminstartion

Administration: 

Oral administration 

fenofibrate is usually taken orally, with or without food. The dose, duration of treatment will depend on the patient’s condition and medical history, as well as the strength and form of the medication prescribed. 

fenofibrate is available in several forms, including tablets and capsules, and may be prescribed as a single agent or in combination with other medications, such as statins. 

Patients should take fenofibrate exactly as prescribed by their healthcare provider and should not adjust the dosage or stop taking the medication without consulting with their provider first. 

If a dose is missed, it is recommended to take it as soon as possible. However, if the next scheduled dose is missed, it should be skipped and the following dose should be taken at the appropriate time. It is important to avoid taking a double dose of the medication to compensate for the missed dose. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: fenofibrate 

Pronounced: [ FEN-oh-FYE-brate] 

Why do we use fenofibrate? 

fenofibrate is a medication used to treat high cholesterol and triglyceride levels in the blood, which are risk factors for cardiovascular disease. It is also used to decrease the risk of pancreatitis in patients with severe hypertriglyceridemia. 

Specifically, fenofibrate is used to: 

• Reduce elevated LDL cholesterol, or “bad” cholesterol levels. 
• Increase HDL cholesterol, or “good” cholesterol levels. 
• Reduce triglyceride levels in the blood. 
• Improve lipid profiles in patients with type 2 diabetes. 
• Decrease the risk of cardiovascular events, like heart attack and stroke, in patients with dyslipidemia and other risk factors. 
• Decrease the risk of pancreatitis in patients with hypertriglyceridemia.