bezafibrate

Bezafibrate is a medication used to regulate the levels of fatty substances (lipids) in the blood. Bezafibrate is an investigational drug, not approved by the FDA, and currently, not commercially available in the U.S.

Bezafibrate is used as an adjunct to diet and other lifestyle measures to reduce high blood levels of triglycerides and the types of cholesterol that increase the risk for plaque buildup in arteries (atherosclerosis), and increase the type of cholesterol that is beneficial to health.

Triglycerides and cholesterols are lipids synthesized in the liver, and are also obtained from our dietary intake. While lipids are essential for many functions in the body, excess circulating levels of lipids in the blood can clog up blood vessels and increase the risk for heart disease, stroke and other diseases. 

Triglycerides are the most common form of fat that the body uses as fuel for energy and to store extra energy. Cholesterol is a waxy combination of lipid and protein (lipoprotein) that the body uses to build cell membranes, produce hormones, bile acids and vitamin D. Low density and very low density lipoproteins (LDL and VLDL) carry cholesterol and triglycerides to cells all over the body, while high density lipoprotein absorbs cholesterol from the cells and transports back to the liver to be converted into bile acids which aid digestion of dietary fat and get excreted.

Bezafibrate reduces the levels of triglycerides, and LDL and VLDL cholesterols, and increases HDL cholesterol levels. Bezafibrate works in the following ways:

• Reduces the synthesis of triglycerides in the liver by inhibiting acetyl-CoA carboxylase, the enzyme involved in fatty acid metabolism
• Decreases cholesterol synthesis by inhibiting 3-hydroxy-3-methyglutaryl-coenzyme A (HMG CoA) reductase, an enzyme required for cholesterol synthesis
• Promotes the activity of lipoprotein lipase, the enzyme that breaks down triglycerides
• The breakdown of triglyceride-rich lipoproteins (VLDL) results in the formation of precursors of HDL cholesterol, resulting in increased HDL levels

In addition, studies show that bezafibrate also reduces the level of fibrinogen, a protein that increases the viscosity of blood and plays a role in blood clot formation. The lowering of lipids and fibrinogen levels reduces the risk of atherosclerosis and cardiovascular disease.

Bezafibrate is used to treat:

• High blood triglyceride levels (hypertriglyceridemia)
• High triglyceride levels and low HDL cholesterol (mixed dyslipidemia)

• Do not use bezafibrate in patients hypersensitive to any of the components of bezafibrate.
• Do not use in patients with a history of photoallergic or phototoxic reactions to fibrates.
• Do not use bezafibrate for the following conditions:
  • Liver function impairment
  • Primary biliary cirrhosis
  • Pre-existing gallbladder disease
  • Kidney function impairment or kidney failure
• Do not use bezafibrate in the treatment of type I hyperlipoproteinemia.
• Do not use it to treat pregnant or breastfeeding women.
• Do not use bezafibrate concurrently with HMG CoA reductase inhibitors (statins) in patients predisposed to muscle disease (myopathy) such as preexisting renal impairment, hormonal or electrolyte imbalance, severe infection, trauma, or surgery.
• Bezafibrate may cause mild decreases in white blood cells, platelets, and hemoglobin levels with initiation of therapy, which may stabilize in the long term.
• Bezafibrate is toxic to the liver. Use with caution in patients with jaundice or liver disorders. Discontinue bezafibrate if:
  • There is no significant response to bezafibrate in 3 months
  • Liver function tests are abnormal and abnormalities persist
  • Patient develops gallstones
• There are rare reports of myopathy, muscle inflammation (myositis), and muscle breakdown (rhabdomyolysis) associated with bezafibrate. Instruct patients to report myopathy symptoms, monitor creatine phosphokinase (CPK) levels, and discontinue if the patient develops myopathy.

Common side effects of bezafibrate include:

• Elevated liver enzyme aspartate aminotransferase (AST)
• Increase in serum creatine phosphokinase
• Gastritis
• Gas (flatulence)
• Indigestion (dyspepsia)
• Diarrhea
• Decreased appetite
• Eczema
• Itching (pruritus)
• Dizziness
• Headache
• Migraine
• Pain
• Insomnia
• Hypersensitivity reaction
• Low red blood cell count (anemia)
• Throat inflammation (pharyngitis)
• Bronchial inflammation (bronchitis)

Less common side effects of bezafibrate include:

• Abdominal distension
• Abdominal pain
• Nausea
• Constipation
• Impaired bile flow (cholestasis)
• Gallstones (cholelithiasis)
• Inflammation of the pancreas (pancreatitis)
• Abnormal liver function test results including:
  • Decrease or increase in serum alkaline phosphatase
  • Increase in serum transaminases
• Increase or decrease in gamma-glutamyl transferase
• Acute kidney injury
• Increase in serum creatinine
• Erectile dysfunction
• Interstitial pulmonary disease
• Muscle cramps
• Muscle inflammation (myositis)
• Muscle pain (myalgia)
• Muscle weakness (myasthenia)
• Numbness and tingling (paresthesia)
• Depression
• Blood disorders including:
  • Low white blood cell count
  • Low platelet count (thrombocytopenia)
  • Immune-mediated low platelet count (immune thrombocytopenia)
  • Low count of all types of blood cells (pancytopenia)
• Skin reactions including:
  • Skin rash
  • Hives (urticaria)
  • Skin photosensitivity
  • Purplish rash from bleeding under the skin (purpuric rash)
• Severe skin reactions including:
  • Erythema multiforme
  • Toxic epidermal necrolysis
  • Stevens-Johnson syndrome
• Hair loss (alopecia)
• Hypersensitivity reactions including:
  • Swelling under the skin and mucous membranes (angioedema)
  • Severe allergic reaction (anaphylaxis)
• Peripheral nerve damage (neuropathy)
• Breakdown of muscles (rhabdomyolysis)

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Oral Tablet, Extended Release

• 400 mg

Adult:

Mixed hyperlipidemia

• Sustained release: 400 mg orally once daily

Hypertriglyceridemia

• Sustained release: 400 mg orally once daily

Dosing Modification

Kidney Impairment

• Creatinine clearance (CrCl) 60 mL/minute or greater: No dosage adjustment required
• CrCl less than 60 mL/minute or serum creatinine is greater than 1.5 mg/dL (greater than 135 micromol/L): Use is contraindicated
• Dialysis: Use is contraindicated

Hepatic Impairment

• Use is contraindicated

Geriatric:

• Patients 70 years of age or below: Refer to adult dosing.
• Patients above 70 years of age: Avoid use in patients above 70 years of age due to declining renal function and the likelihood of CrCl below 60 mL/minute in this population.

Pediatric:

Dyslipidemia

• Children and Adolescents: 10 to 20 mg/kg/day (maximum: 400 mg daily) orally
• Note: Limited experience available; use caution. Based on child’s weight, dosing may not be possible as the sustained release tablet must be administered whole

Dosage adjustment for concomitant therapy

• Significant drug interactions exist, requiring dose/frequency adjustment or avoidance

Administration

• Do not crush or chew tablet; should be swallowed whole with sufficient fluid
• Administer in morning or evening with or after meals
• Take a missed dose as soon as remembered unless it is almost time for the next dose, then skip the missed dose and continue your regular dosing schedule; do not take 2 doses at the same time.
• Bariatric surgery (adult): Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Cannot be cut or crushed. Switch to fenofibrate tablet.

• Adverse effects of bezafibrate overdose, except for muscle breakdown (rhabdomyolysis) are not known.
• There is no known specific antidote for bezafibrate.
• Overdose may be treated with symptomatic and supportive care.
• In the case of rhabdomyolysis, bezafibrate is discontinued immediately and kidney function is carefully monitored.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe interactions of bezafibrate include:
  • ciprofibrate
  • ezetimibe
  • monoamine oxidase inhibitors (MAOIs)
• Serious interactions of bezafibrate include:
  • bile acid sequestrants
  • cyclosporine
  • statins
  • warfarin (vitamin K antagonists)
• Moderate interactions of bezafibrate include:
  • acipimox
  • colchicine
  • mizoribine
  • raltegravir
  • sulfonylureas
• Bezafibrate has no known mild interactions with other drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider about all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• There are insufficient animal reproductive studies and no adequate, well-controlled studies of bezafibrate use in pregnant women, avoid use.
• Women of pregnancy potential should use effective contraception during bezafibrate therapy and for several months after discontinuation.
• It is not known if bezafibrate is present in breast milk. Decision should be made to discontinue nursing or bezafibrate, taking into account the importance of the drug to the mother, because of the potential for serious adverse effects in the breastfed infant.

• Take bezafibrate exactly as prescribed.
• Bezafibrate is not a substitute for a heart-healthy diet. For effective maintenance of healthy lipid levels, along with bezafibrate therapy it is important to:
  • Eat low fat, low cholesterol diet
  • Maintain healthy weight
  • Exercise regularly
  • Avoid smoking
• Bezafibrate can cause muscle damage. Report to your physician immediately if you experience unexplained muscle pain, tenderness, weakness, or brown urine.
• Store safely out of reach of children.
• In case of overdose, seek medical help or contact Poison Control.