Can a patient use ezetimibe and Tricor (fenofibrate) together?

Can a Patient Use Ezetimibe and Tricor (Fenofibrate) Together?

Yes, ezetimibe and fenofibrate (Tricor) can be used together safely and effectively, particularly in patients with mixed hyperlipidemia who have both elevated LDL-cholesterol and triglycerides. 1

FDA-Approved Combination

• The FDA explicitly approves ezetimibe in combination with fenofibrate as an adjunct to diet to reduce elevated LDL-C in adults with mixed hyperlipidemia. 1
• This combination is listed in the official prescribing information for ezetimibe, indicating regulatory approval for concurrent use. 1

Clinical Efficacy Evidence

Lipid Parameter Improvements:

• The combination of fenofibrate 160 mg plus ezetimibe 10 mg produces significantly greater LDL-C reduction (-36.2%) compared to fenofibrate alone (-22.4%) or ezetimibe alone (-22.8%) in patients with mixed hyperlipidemia. 2
• Non-HDL-cholesterol decreases by 36.2% with combination therapy versus 24.8% with fenofibrate alone and 20.9% with ezetimibe alone. 2
• The combination reduces triglycerides by 44% and increases HDL-C by 19%, addressing the complete lipid profile in mixed hyperlipidemia. 3
• Apolipoprotein B decreases by 33.3% with combination therapy compared to 24.5% with fenofibrate alone and 18.7% with ezetimibe alone. 2

LDL Particle Size Benefits:

• Over 70% of patients with mixed hyperlipidemia exhibit the atherogenic small, dense LDL pattern B profile at baseline. 3
• Both fenofibrate-containing regimens shift patients from the more atherogenic small, dense LDL pattern to larger, more buoyant, less atherogenic LDL particles. 3

Safety Profile

Long-Term Safety Data:

• A 48-week extension study demonstrated that fenofibrate plus ezetimibe was well tolerated with similar safety profiles to fenofibrate monotherapy. 4
• Consecutive elevations of ALT/AST ≥3 times upper limit of normal occurred in only 1.2% of combination therapy patients versus 1.7% on fenofibrate alone. 4
• No cases of creatine phosphokinase elevations ≥10 times upper limit of normal or myopathy were observed in either treatment group during long-term follow-up. 4

Pharmacokinetic Interaction:

• Coadministration of fenofibrate and ezetimibe has no statistically significant effect on fenofibric acid pharmacokinetics. 5
• While fenofibrate increases total ezetimibe exposure by approximately 43-49%, this interaction does not translate into increased adverse events in clinical trials. 5

Clinical Application Algorithm

For Mixed Hyperlipidemia (Elevated LDL-C and Triglycerides):

1. Initial Assessment: Confirm LDL-C ≥3.4 mmol/L (130 mg/dL) and triglycerides 2.3-5.7 mmol/L (200-500 mg/dL). 3

2. Dosing Regimen: Administer fenofibrate 145-160 mg plus ezetimibe 10 mg once daily, with or without food. 1, 2

3. Monitoring Schedule:

   • Assess lipid panel at 4-6 weeks after initiation. 6
   • Perform liver enzyme testing at baseline and as clinically indicated. 1
   • Monitor for muscle symptoms (myalgia, weakness) throughout treatment. 1

4. Target Goals: Aim for LDL-C <100 mg/dL (or <70 mg/dL in very high-risk patients) and triglycerides <150 mg/dL. 6

Important Caveats and Monitoring

Gallbladder Considerations:

• If cholelithiasis is suspected in a patient receiving ezetimibe and fenofibrate, gallbladder studies are indicated and alternative lipid-lowering therapy should be considered. 1
• This is particularly relevant given fenofibrate's known association with increased cholesterol saturation of bile. 1

Hepatic Monitoring:

• Perform liver enzyme testing before initiating combination therapy and as clinically indicated during treatment. 1
• Consider withdrawal of ezetimibe if increases in ALT or AST ≥3 times upper limit of normal persist. 1

Contraindications:

• Do not use in patients with hypersensitivity to either ezetimibe or fenofibrate. 1
• Avoid in patients with moderate to severe hepatic impairment. 1
• Refer to fenofibrate prescribing information for additional contraindications including severe renal dysfunction and active liver disease. 1

Drug Interaction Management:

• If bile acid sequestrants are also prescribed, administer ezetimibe either ≥2 hours before or ≥4 hours after the bile acid sequestrant to avoid reduced ezetimibe absorption. 1
• Avoid combining with gemfibrozil specifically, as this fibrate has higher myopathy risk when combined with other lipid-lowering agents compared to fenofibrate. 6

Guideline Support for Combination Therapy

• The 2022 ACC Expert Consensus supports combination therapy with ezetimibe and other non-statin agents for patients not achieving LDL-C goals on maximally tolerated statin therapy. 6
• European guidelines recognize that combination therapy with ezetimibe and fibrates (particularly fenofibrate) can further lower LDL-C when applied together, with the recommendation to take fibrates in the morning and other agents in the evening to minimize peak dose concentrations. 6
• The 2024 International Lipid Expert Panel recommends combination therapy approaches for patients with metabolic syndrome and diabetes, populations that frequently present with mixed hyperlipidemia. 6