Usage
Bezafibrate is prescribed as an adjunctive therapy to diet and other non-pharmacological interventions for managing specific lipid disorders, primarily:
- Hypercholesterolemia (Type IIa and IIb): Characterized by elevated total and LDL cholesterol levels.
- Mixed Hyperlipidemia (Type IIb and IV): Involves elevated cholesterol and triglyceride levels.
- Hypertriglyceridemia (Type IV and V): Marked by significantly high triglyceride levels, particularly in patients at high risk of complications like pancreatitis.
Pharmacological Classification: Bezafibrate is classified as a fibrate, a type of lipid-lowering agent.
Mechanism of Action: Bezafibrate primarily activates peroxisome proliferator-activated receptor alpha (PPARα). This activation influences multiple genes involved in lipid metabolism, resulting in decreased triglyceride production in the liver and increased triglyceride clearance from circulation. It also increases HDL cholesterol and may reduce LDL cholesterol and apolipoprotein B, although the LDL-lowering effect can vary depending on the individual’s lipid profile.
Alternate Names
Bezafibrate is the generic name. Brand names include Bezalip, Bezalip Retard, Bezalip Mono, and Fibrazate XL.
How It Works
Pharmacodynamics: Bezafibrate exerts its lipid-lowering effects through PPARα activation, modulating lipoprotein metabolism. Key effects include:
- Triglyceride Reduction: Decreases hepatic triglyceride production and increases peripheral clearance via lipoprotein lipase stimulation.
- HDL Increase: Enhances Apo A-I and Apo A-II production, leading to increased HDL levels.
- LDL Modulation: May decrease LDL, especially small, dense LDL particles, but can sometimes increase LDL in patients with predominantly high triglycerides and low LDL at baseline.
- Fibrinogen Reduction: May decrease fibrinogen levels and blood viscosity.
- Glucose Modulation: May improve glucose tolerance in some diabetic patients.
Pharmacokinetics:
- Absorption: Bezafibrate is well-absorbed orally. Food slows but doesn’t significantly reduce overall absorption.
- Metabolism: Undergoes extensive hepatic metabolism, with minimal unchanged drug excreted.
- Elimination: Primarily excreted renally (95%), with a small fraction in bile. Elimination is delayed in patients with renal impairment.
Mode of Action (Cellular/Molecular): Binds to and activates PPARα, a nuclear receptor that regulates the transcription of genes involved in lipid metabolism. This results in increased lipoprotein lipase activity, decreased Apo C-III synthesis, and increased Apo A-I and A-II synthesis.
Elimination Pathways: Primarily renal excretion of metabolites.
Dosage
Standard Dosage
Adults:
- Conventional Tablets (Bezalip): 200 mg three times a day, taken with or after meals. May be gradually increased over 5-7 days to minimize gastrointestinal side effects.
- Sustained-Release Tablets (Bezalip Retard, Bezalip Mono, Fibrazate XL): 400 mg once daily, swallowed whole with fluid, with or after a meal. Do not crush or chew.
Children:
Limited experience; use with caution. Dosage ranges from 10-20 mg/kg/day. Long-term safety in children is not established.
Special Cases:
- Elderly Patients: Dose adjustment is required due to age-related decline in renal function. Bezalip Retard 400 mg is generally not recommended in patients over 70 years old.
- Patients with Renal Impairment: Dosage must be reduced based on creatinine clearance. Sustained-release formulations are contraindicated if CrCl < 60 mL/min. Conventional tablets are contraindicated if CrCl < 15 mL/min. Dialysis patients should not use bezafibrate.
- Patients with Hepatic Dysfunction: Contraindicated in moderate to severe hepatic impairment.
- Patients with Comorbid Conditions: Consider potential drug interactions, especially with anticoagulants, antidiabetic agents, and statins.
Clinical Use Cases
Bezafibrate is not specifically indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations like status epilepticus or cardiac arrest. Its primary role is in managing chronic lipid disorders.
Dosage Adjustments
Adjust based on renal function, age, and concomitant medications. Monitor creatinine phosphokinase (CPK), liver function tests (LFTs), and renal function during therapy.
Side Effects
Common Side Effects:
Gastrointestinal upset (nausea, diarrhea, abdominal pain, flatulence), dizziness, headache, itching, rash.
Rare but Serious Side Effects:
Myopathy/rhabdomyolysis (especially with statin co-administration or renal impairment), hepatotoxicity (elevated liver enzymes), gallstones, hypersensitivity reactions (including angioedema and anaphylaxis), pancreatitis, blood dyscrasias (decreased hemoglobin, white blood cells, and platelets).
Long-Term Effects:
Potential for gallstone formation, myopathy with long-term use, especially in combination with statins.
Adverse Drug Reactions (ADR):
Rhabdomyolysis, hepatotoxicity, severe allergic reactions.
Contraindications
- Severe hepatic impairment (including primary biliary cirrhosis).
- Pre-existing gallbladder disease.
- Severe renal impairment (CrCl < 15 mL/min for conventional tablets, < 60 mL/min for sustained-release). Dialysis patients.
- Pregnancy and breastfeeding.
- Hypersensitivity to bezafibrate or other fibrates.
- Concurrent use of MAO inhibitors.
Drug Interactions
- Anticoagulants (e.g., warfarin): Enhanced anticoagulant effect; dose reduction may be needed.
- Statins: Increased risk of myopathy/rhabdomyolysis; monitor CPK levels.
- Antidiabetic agents (e.g., insulin, sulfonylureas): May enhance glucose-lowering effects.
- Bile acid sequestrants (e.g., cholestyramine): Reduced bezafibrate absorption; administer at least 2 hours apart.
- Immunosuppressants (e.g., ciclosporin): Increased risk of renal impairment.
- Estrogens: May diminish bezafibrate’s effectiveness.
Pregnancy and Breastfeeding
Contraindicated in pregnancy due to potential fetal harm. Not recommended during breastfeeding.
Drug Profile Summary
- Mechanism of Action: PPARα agonist, reducing triglycerides, increasing HDL, modulating LDL.
- Side Effects: GI upset, dizziness, headache, myopathy, hepatotoxicity, gallstones.
- Contraindications: Hepatic/renal impairment, gallbladder disease, pregnancy/breastfeeding.
- Drug Interactions: Warfarin, statins, antidiabetic agents, cholestyramine, ciclosporin.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: 200 mg TID (conventional) or 400 mg OD (sustained-release).
- Monitoring Parameters: LFTs, CPK, renal function, lipid profile.
Popular Combinations
Sometimes used with statins in patients with mixed dyslipidemia who don’t respond adequately to statin monotherapy, but this combination carries an increased risk of myopathy.
Precautions
- Monitor liver and kidney function.
- Caution in patients with a history of muscle disorders or taking other drugs that can cause myopathy.
- Advise patients to report muscle pain or weakness immediately.
- Patients with renal impairment require dose reduction.
- Contraindicated in pregnancy and breastfeeding.
- Alcohol consumption may increase the risk of hepatic and muscular side effects.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Bezafibrate?
A: For adults, 200 mg three times a day (conventional tablets) or 400 mg once a day (sustained-release tablets). Dose adjustment necessary for renal impairment and elderly patients.
Q2: How should Bezafibrate be taken?
A: With or after meals. Sustained-release tablets must be swallowed whole, not crushed or chewed.
Q3: What are the common side effects?
A: Gastrointestinal upset (nausea, diarrhea, abdominal pain), dizziness, headache, pruritus, and skin rash.
Q4: What are the serious side effects of Bezafibrate?
A: Myopathy/rhabdomyolysis, hepatotoxicity, gallstones, pancreatitis, and serious allergic reactions.
Q5: Can Bezafibrate be used during pregnancy or breastfeeding?
A: No, it is contraindicated.
Q6: What drugs interact with Bezafibrate?
A: Anticoagulants (e.g., warfarin), statins, antidiabetic medications, bile acid sequestrants (e.g., cholestyramine), and immunosuppressants (e.g., ciclosporin).
Q7: How does Bezafibrate affect renal function?
A: It is primarily excreted by the kidneys. Dosage adjustment is required in renal impairment, and it is contraindicated in severe renal disease and dialysis patients. May also cause an increase in serum creatinine levels, requiring monitoring.
Q8: What is the role of Bezafibrate in treating hypertriglyceridemia?
A: It is particularly effective in lowering triglyceride levels by decreasing hepatic production and increasing peripheral clearance.
Q9: When should Bezafibrate be discontinued?
A: If no significant lipid response is observed within 3-4 months, if serious side effects occur, or in conditions where it is contraindicated (e.g., pregnancy).
Q10: What lifestyle modifications should be recommended with Bezafibrate?
A: Diet, exercise, and weight loss in obese patients. Control of other risk factors like smoking, excessive alcohol intake, and uncontrolled hypertension.
