Overview
Ezetimibe is a cholesterol absorption inhibitor used as adjunctive therapy to diet for reducing elevated LDL-C in patients with primary hyperlipidemia, including familial hypercholesterolemia. It works by selectively inhibiting intestinal cholesterol absorption without affecting fat-soluble vitamin absorption. It can be used alone or in combination with statins and other lipid-lowering therapies.
Mechanism of Action
Selectively inhibits intestinal cholesterol absorption at the brush border of the small intestine via the NPC1L1 transporter, reducing delivery of intestinal cholesterol to the liver and decreasing hepatic cholesterol stores while increasing clearance of cholesterol from the blood.
Indications
- Adjunct to diet to reduce elevated LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH)
- Adjunct to diet to reduce elevated LDL-C in pediatric patients 10+ years with HeFH (in combination with statin)
- Adjunct to diet to reduce elevated LDL-C in adults with mixed hyperlipidemia (in combination with fenofibrate)
- Reduce elevated LDL-C in adults and pediatric patients 10+ years with homozygous familial hypercholesterolemia (HoFH) (in combination with statin and other therapies)
- Reduce elevated sitosterol and campesterol levels in adults and pediatric patients 9+ years with homozygous familial sitosterolemia
Common Doses
- 10 mg
Dosage
10 mg orally once daily, with or without food. If a dose is missed, take as soon as possible without doubling the next dose. Administer at least 2 hours before or 4 hours after bile acid sequestrants. Assess LDL-C response as early as 4 weeks after initiation.
Contraindications
- Known hypersensitivity to ezetimibe or any excipients
- When used in combination: contraindicated if the concomitant therapy (statin, fenofibrate, or other LDL-C lowering therapy) is contraindicated
Side Effects
- Common: Headache, diarrhea, upper respiratory tract infection, arthralgia, sinusitis
- Serious: Hypersensitivity reactions (anaphylaxis, angioedema, rash, urticaria), liver enzyme abnormalities, rhabdomyolysis/myopathy, cholelithiasis (with fibrates)
Interactions
- Cyclosporine: Increases concentrations of both drugs; monitor cyclosporine levels
- Fibrates: May increase risk of cholelithiasis; co-administration with fibrates other than fenofibrate not recommended
- Bile acid sequestrants: Decrease ezetimibe absorption; administer ezetimibe at least 2 hours before or 4 hours after
Counseling Points
- Take once daily with or without food
- Do not double dose if missed; take as soon as remembered
- Separate from bile acid sequestrants by 2-4 hours
- Report unexplained muscle pain, tenderness, weakness, or dark urine immediately
- Continue dietary management and exercise program
- Regular monitoring of cholesterol levels is important