Ezetimibe Combination Therapy with Rosuvastatin and Fenofibrate

Introduction to Combination Therapy

• The American College of Cardiology recognizes ezetimibe in combination with fenofibrate as appropriate for managing mixed hyperlipidemia 1

FDA-Approved Indications

• The FDA approves ezetimibe for use in combination with fenofibrate as adjunct to diet to reduce elevated LDL-C in adults with mixed hyperlipidemia 1

Evidence for Ezetimibe Plus Rosuvastatin

• The I-ROSETTE trial showed that fixed-dose combinations of ezetimibe 10 mg with rosuvastatin achieved LDL-C reductions >50% from baseline with safety and tolerability comparable to rosuvastatin monotherapy 2, 3, 4
• The ACTE study demonstrated that adding ezetimibe 10 mg to stable rosuvastatin 5 or 10 mg produced greater LDL-C reductions and better goal achievement compared with up-titrating rosuvastatin doses, with comparable adverse event profiles 2, 3, 4

Safety and Monitoring

• The incidence of consecutive elevations (≥3× ULN) of hepatic transaminases is 1.3% with ezetimibe plus statins versus 0.4% with statins alone 1
• The American College of Cardiology recommends monitoring for myopathy/rhabdomyolysis risk when combining ezetimibe with statins or fibrates, with cases reported in patients taking statins or fibrates 1

Dosing and Administration

• Ezetimibe should be administered at a dose of 10 mg orally once daily, with or without food, when used in combination with rosuvastatin and fenofibrate 1
• Rosuvastatin should be started at a dose of 5-10 mg daily and can be titrated to 20 mg based on LDL-C response 2, 3
• Fenofibrate should be used at standard dosing per product labeling, adjusted for renal function 1