Ezetimibe

A to Z Drug Facts

 Action Inhibits absorption of cholesterol by the small intestine.

Absorption: C_max is 3.4 to 5.5 ng/mL (ezetimibe) and 45 to 71 ng/mL (metabolite). T_max is 4 to 12 hr (ezetimibe) and 1 to 2 hr (metabolite).

Distribution: More than 90% protein bound.

Metabolism: Metabolized (active) in small intestine and liver to ezetimibe glucoronide.

Elimination: The t_½ is approximately 22 hr. Approximately 78% is excreted in feces and 11% in urine.

Elderly: Plasma concentrations are approximately 2-fold higher.

Hepatic function impairment: AUC increased approximately 1.7-fold in those with mild insufficiency, 3- to 4-fold in moderate insufficiency and 5- to 6-fold in severe impairment.

Renal function impairment: AUC increased approximately 1.5-fold in those with severe renal disease (Ccr up to 30 mL/min).

 Indications Administration alone or with HMG-CoA reductase inhibitors as adjunctive therapy to diet for reduction of elevated total cholesterol, low density lipoprotein cholesterol (LDL), and apolipoprotein in patients with primary hypercholesterolemia; with atorvastatin or simvastatin for the reduction of elevated total cholesterol and LDL levels in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments or if such treatments are unavailable; as adjunctive therapy to diet for the reduction of elevated sitosterol and campesterol levels in patients with homozygous familial sitosterolemia.

 Contraindications Ezetimibe is contraindicated in combination with HMG-CoA reductase inhibitors in patients with active liver disease or unexplained persistent elevations in serum transaminases; hypersensitivity to any component of the product.

 Route/Dosage

Adults and children over 10 yr: PO 10 mg once daily.

 Interactions

Antacids: Aluminum- and magnesium-containing antacids decrease the peak concentration of ezetimibe but not the AUC. Cholestyramine: The AUC of ezetimibe may be decreased. Cyclosporine, fibric acid derivatives (eg, fenofibrate, gemfibrozil): Concentrations of ezetimibe may be increased.

 Lab Test Interferences None well documented.

 Adverse Reactions

CNS: Fatigue; headache; dizziness. EENT: Sinusitis; pharyngitis. GI: Diarrhea; abdominal pain. RESPIRATORY: Coughing; upper respiratory tract infection. OTHER: Back pain; arthralgia; viral infection; myalgia; chest pain.

 Precautions

Pregnancy: Category C. Lactation: Undetermined. Children: Safety and efficacy not established in children under 10 yr. Secondary causes of hyperlipidemia: Ruled out or treat secondary causes of hyperlipidemia before starting treatment with ezetimibe. Hepatic impairment: Use not recommended because of unknown effects on liver.

 Administration/Storage

• Give prescribed dose once daily with or without food.
• Administer alone or in combination with other lipid-lowering therapy.
• May be administered at the same time as an HMG-CoA reductase inhibitor.
• Administer 2 hr before or 4 hr after a bile acid sequestrant.
• Store tablets at controlled room temperature (59° to 86°F). Protect from moisture.

 Assessment/Interventions

• Obtain patient history, including drug history and any known allergies. Note presence of active liver disease or moderate to severe hepatic insufficiency.
• Ensure that patient is on a cholesterol-lowering diet.
• Ensure that lipids are measured before therapy is started and periodically during therapy.
• Assess patient for GI, musculoskeletal, respiratory, and general body side effects. If noted and significant, inform health care provider.

 Patient/Family Education

• Explain name, dose, action, and potential side effects of drug.
• Advise patient to review “Patient Information about Zetia ” before starting the medication and each time when refilling the medication.
• Advise patient to take once daily as prescribed, without regard to meals.
• Advise patient to try to take each dose at about the same time each day.
• Inform patient that drug helps control, but not does cure, cholesterol abnormality and to continue taking drug as prescribed if cholesterol levels are lowered.
• Caution patient not to change the dose or stop taking unless advised by health care provider.
• Advise patient that if a dose is missed to take as soon as remembered but to never take more than 1 dose of medicine a day.
• Instruct patient to continue taking other cholesterol-lowering medications as prescribed by health care provider.
• Emphasize to patient importance of the following other modalities on cholesterol control: dietary changes (eg, reduced saturated fat intake, increase soluble fiber intake); weight control, regular exercise, and smoking cessation.
• Advise women to contact health care provider if pregnant, planning to become pregnant, or breastfeeding.
• Caution patient to not take any prescription or OTC medications or dietary supplements unless advised by health care provider.
• Instruct patient to notify health care provider if experiencing any unexplained muscle pain, tenderness, or weakness or noting any other unusual feelings.
• Advise patient that follow-up visits and lab tests will be required to monitor therapy and to keep appointments.

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Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts