Fenofibrate

# Fenofibrate ## Overview - **Classification**: Fibrate (Fibric Acid Derivative) - **Mechanism**: Activates peroxisome proliferator-activated receptor alpha (PPAR-alpha). This increases lipoprotein lipase activity, enhancing triglyceride breakdown and reducing VLDL levels. It also increases HDL-C. ## Primary Indications 1. **Severe Hypertriglyceridemia** - To reduce the risk of pancreatitis in adults with TG ≥ 500 mg/dL. 2. **Primary Hypercholesterolemia or Mixed Dyslipidemia** - As adjunctive therapy to diet in adults. 3. **Hypertriglyceridemia** - As adjunctive therapy to diet in adults with TG ≥ 200 mg/dL. ## Adult Dosing ### Standard Dosing **Primary Hypercholesterolemia or Mixed Dyslipidemia** - **Dose**: **145 mg** (Fenofibrate, nanoparticles) or **48 mg** (Fenofibric Acid DR) - **Frequency**: Once daily - **Route**: Oral **Severe Hypertriglyceridemia** - **Dose**: **145 mg** (Fenofibrate, nanoparticles) or **48 mg** (Fenofibric Acid DR) - **Frequency**: Once daily - **Route**: Oral - **Special Considerations**: Some formulations (e.g., TriCor) recommend taking with food for optimal absorption. ### Dose Adjustments - **Renal Impairment**: - CrCl 30-59 mL/min: Reduce dose to **48 mg** (Fenofibrate, nanoparticles) once daily. - CrCl <30 mL/min: **Contraindicated.** - **Hepatic Impairment**: Not recommended in active liver disease. - **Elderly Patients**: No specific adjustment; follow renal function guidelines. ## Pediatric Dosing *Fenofibrate is generally not recommended for pediatric use due to limited data on safety and efficacy.* ### Neonates (0-28 days) - **Dose**: Not recommended. - **Special Notes**: Safety and efficacy not established in this age group. ### Infants (1-12 months) - **Dose**: Not recommended. - **Special Notes**: Safety and efficacy not established in this age group. ### Children (1-12 years) - **Dose**: Not recommended. - **Special Notes**: Safety and efficacy not established in this age group. ### Adolescents (13-18 years) - **Dose**: Data limited; use with caution under specialist guidance. - **Frequency**: Once daily (if used) - **Route**: Oral - **Maximum**: Adult dose (**145 mg**) - **Special Notes**: Generally reserved for severe cases unresponsive to lifestyle and other therapies. ## Safety Information ### Contraindications - **Absolute**: Severe renal impairment (CrCl < 30 mL/min) - **Absolute**: Active liver disease, including primary biliary cirrhosis - **Absolute**: Pre-existing gallbladder disease - **Absolute**: Nursing mothers - **Absolute**: Hypersensitivity to fenofibrate or fenofibric acid ### Common Adverse Effects - **Very Common (>10%)**: Elevated liver enzymes (AST/ALT) - **Common (1-10%)**: Abdominal pain, nausea, constipation, diarrhea, headache, back pain, increased creatinine. - **Serious but Rare**: Myopathy/Rhabdomyolysis, cholelithiasis, pancreatitis, severe skin reactions (SJS, TEN), venous thromboembolism. ### Key Drug Interactions - **Statins (HMG-CoA Reductase Inhibitors)**: Increased risk of myopathy/rhabdomyolysis. - **Monitoring**: Monitor for muscle pain/weakness, check CK levels. - **Oral Anticoagulants (e.g., Warfarin)**: Enhances anticoagulant effect, increasing bleeding risk. - **Monitoring**: Frequent INR checks upon initiation, dose change, or discontinuation. - **Bile Acid Sequestrants (e.g., Cholestyramine)**: Reduced fenofibrate absorption. - **Monitoring**: Administer fenofibrate 1 hr before or 4-6 hrs after sequestrant. - **Immunosuppressants (e.g., Cyclosporine)**: May worsen renal function. - **Monitoring**: Monitor renal function closely. ## Monitoring & Follow-up - **Before Treatment**: Baseline LFTs (AST/ALT), CrCl, lipid panel (TG, HDL-C, LDL-C). - **During Treatment**: LFTs q3 months for 1st year, then periodically. CrCl periodically. Lipid panel q4-12 weeks until goal, then periodically. - **Clinical Signs**: Watch for muscle pain, tenderness, weakness; signs of cholelithiasis (e.g., severe abdominal pain); unexplained fatigue, dark urine, jaundice. ## Clinical Pearls - 💡 **Tip 1**: Some fenofibrate products (e.g., TriCor) should be taken with food to optimize absorption. Check specific product labeling. - 💡 **Tip 2**: Fenofibrate is often used when statins are contraindicated, poorly tolerated, or for severe hypertriglyceridemia. - 💡 **Tip 3**: Counsel patients on muscle pain/weakness; advise them to report symptoms immediately. - 💡 **Tip 4**: Not indicated for the sole purpose of primary prevention of cardiovascular disease. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.