What is the treatment for a patient with hypertriglyceridemia?

Fenofibrate Dosing for Hypertriglyceridemia

Recommended Dosing by Severity

For severe hypertriglyceridemia (≥500 mg/dL), initiate fenofibrate 54-160 mg daily immediately to prevent acute pancreatitis, with the FDA-approved initial dose range of 54-160 mg per day, individualized based on patient response and assessed at 4-8 week intervals. 1, 2, 3

Severe to Very Severe Hypertriglyceridemia (≥500 mg/dL)

• Start fenofibrate 54-160 mg once daily immediately as first-line therapy before addressing LDL cholesterol, as this level carries a 14% risk of acute pancreatitis and requires urgent intervention 1, 2, 3
• Fenofibrate provides 30-50% triglyceride reduction at these doses 1, 2, 4
• The maximum FDA-approved dose is 160 mg once daily 3
• Reassess lipid panel at 4-8 week intervals after initiating therapy to guide dose adjustments 1, 3

Moderate Hypertriglyceridemia (200-499 mg/dL)

• For patients with moderate hypertriglyceridemia and mixed dyslipidemia, the FDA-approved initial dose is 160 mg once daily 3
• Consider fenofibrate 54-160 mg daily if triglycerides remain >200 mg/dL after 3 months of optimized lifestyle modifications and statin therapy 1
• Fenofibrate is particularly indicated when HDL-C is low (<40 mg/dL for men, <50 mg/dL for women) and cardiovascular risk is elevated 1

Critical Dose Adjustments

Renal Impairment

Patients with mild to moderate renal impairment (eGFR 30-59 mL/min/1.73 m²) must start at 54 mg daily and should not exceed this dose. 1, 3

• For eGFR ≥60 mL/min/1.73 m²: Start 54 mg daily, may titrate up to 160 mg daily based on response 1
• For eGFR 30-59 mL/min/1.73 m²: Start and maintain at 54 mg daily maximum 1, 3
• For eGFR <30 mL/min/1.73 m²: Fenofibrate is contraindicated 3
• Monitor renal function within 3 months after initiation and every 6 months thereafter 1
• If eGFR persistently decreases to <30 mL/min/1.73 m², discontinue fenofibrate immediately 1

Elderly Patients

• Dose selection should be based on renal function, as elderly patients frequently have reduced creatinine clearance 3
• Start at 54 mg daily in elderly patients with any degree of renal impairment 1

Administration Guidelines

• Fenofibrate must be taken with meals to optimize bioavailability 3
• Administer once daily, swallowing tablets whole 3
• When combining with statins, take fenofibrate in the morning and statins in the evening to minimize peak dose concentrations 1

Monitoring Strategy

• Obtain baseline fasting lipid panel, liver enzymes, and creatine kinase before initiating therapy 1
• Reassess fasting lipid panel at 4-8 weeks after starting or adjusting dose 1, 3
• Monitor liver enzymes and creatine kinase at baseline and 3 months after initiation 1
• Check renal function within 3 months, then every 6 months 1
• Withdraw therapy if no adequate response after 2 months at maximum dose (160 mg daily) 3

Combination Therapy Considerations

With Statins

• When combining fenofibrate with statins, use lower statin doses (atorvastatin 10-20 mg maximum) to minimize myopathy risk 1, 2
• Use fenofibrate, NOT gemfibrozil, when combining with statins due to significantly better safety profile 1, 2
• Monitor for muscle symptoms and obtain creatine kinase levels, especially in patients >65 years or with renal disease 1

With Omega-3 Fatty Acids

• Prescription omega-3 fatty acids (icosapent ethyl 2-4g daily) can be added as adjunctive therapy if triglycerides remain >200 mg/dL after fenofibrate optimization 1, 2
• This combination is particularly indicated for patients with established cardiovascular disease or diabetes with ≥2 additional risk factors 1, 2

Common Pitfalls to Avoid

• Do not delay fenofibrate initiation while attempting lifestyle modifications alone when triglycerides are ≥500 mg/dL—pharmacologic therapy is mandatory to prevent pancreatitis 1, 2
• Do not start with statin monotherapy when triglycerides are ≥500 mg/dL, as statins provide only 10-30% triglyceride reduction, insufficient for pancreatitis prevention 1, 2
• Do not use fenofibrate in patients with active liver disease, preexisting gallbladder disease, or severe renal impairment 3
• Do not reduce fenofibrate dose prematurely—maintain maximum tolerated dose based on renal function until lipid goals are achieved 1