General

Pronunciation:
e-zet-i-mibe

Trade Name(s)

• Ezetrol 
• Zetia

Ther. Class.

lipid-lowering agents

Pharm. Class.

cholesterol absorption inhibitors

Indications

• Primary hyperlipidemia, including heterozygous familial hypercholesterolemia (as monotherapy [in adults only] or in combination with a statin).
• Mixed hyperlipidemia (in combination with fenofibrate).
• Homozygous familial hypercholesterolemia (in combination with a statin and other low-density lipoprotein cholesterol [LDL-C] lowering therapies).
• Familial sitosterolemia.

Action

Inhibits absorption of cholesterol in the small intestine.

Therapeutic Effect(s):

• Reduction of LDL-C concentrations.
• Reduction of sitosterol and campesterol concentrations.

Pharmacokinetics

Absorption: Following absorption, rapidly converted to ezetimibe-glucuronide, which is active. Bioavailability is variable.

Distribution: Unknown.

Metabolism and Excretion: Undergoes enterohepatic recycling, mostly eliminated in feces, minimal renal excretion.

Half-life: 22 hr.

TIME/ACTION PROFILE

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity;
• When a statin, fenofibrate, or other LDL-C lowering therapy is contraindicated (when used in combination with statin, fenofibrate, or other LDL-C lowering therapy);
• Moderate or severe hepatic impairment;

Use Cautiously in:

• OB:  Safety not established in pregnancy;
• Lactation: Safety not established in breastfeeding;
• Pedi:  Children <10 yr (safety and effectiveness not established).

Adverse Reactions/Side Effects

Derm: rash

GI: ↑ liver enzymes, cholecystitis, cholelithiasis, nausea, pancreatitis

MS: myopathy, RHABDOMYOLYSIS

Misc: ANGIOEDEMA

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

• Effects may be ↓ by  cholestyramine  or other  bile acid sequestrants.
• Concurrent use of  fibrates  may ↑ levels and the risk of cholelithiasis.
•  Cyclosporine  may ↑ levels.
• May ↑ risk of rhabdomyolysis when used with  HMG CoA-reductase inhibitors.

Route/Dosage

PO (Adults): 10 mg once daily.

Renal Impairment 
PO (Adults): CCr <60 mL/min and concurrent use with simvastatin: Not to exceed simvastatin dose of 20 mg/day.

Availability (generic available)

Tablets: 10 mg

In Combination with: rosuvastatin (Roszet); simvastatin (Vytorin); see combination drugs.

Assessment

• Obtain a diet history, especially with regard to fat consumption.

Lab Test Considerations:

Evaluate serum cholesterol and triglyceride levels before initiating, after 2–4 wk of therapy, and periodically thereafter.

• May cause ↑ liver transaminases when administered with HMG-CoA reductase inhibitors. Monitor liver enzymes prior to initiation and during therapy according to recommendations of HMG-CoA reductase inhibitor. Elevations are usually asymptomatic and return to baseline with continued therapy.

Implementation

• Do not confuse Zetia with Zestril.

• PO Administer without regard to meals. May be taken at the same time as HMG-CoA reductase inhibitors or fenofibrate. Administer at least 2 hr before or at least 4 hr after bile acid sequestrants.

Patient/Family Teaching

• Instruct patient to take ezetimibe as directed, at the same time each day, even if feeling well. Take missed doses as soon as remembered, but do not take more than 1 dose/day. Medication helps control but does not cure elevated serum cholesterol levels. Advise patient to read  Patient Information  before starting therapy and with each Rx refill in case of change.
• Advise patient that this medication should be used in conjunction with diet restrictions (fat, cholesterol, carbohydrates, alcohol), exercise, and cessation of smoking. Ezetimibe does not assist with weight loss.
• Instruct patient to notify health care professional if unexplained muscle pain, tenderness, or weakness occur. Risk may increase when used with HMG-CoA reductase inhibitors.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking any other Rx, OTC, or herbal products.
• Advise patient to notify health care professional of medication regimen prior to treatment or surgery.
• Rep:  Advise females of reproductive potential to notify health care professional promptly if pregnancy is planned or suspected or if breastfeeding. If regimen includes HMG-CoA reductase inhibitors, they are contraindicated in pregnancy.
• Emphasize the importance of follow-up exams to determine effectiveness and to monitor for side effects.

Evaluation/Desired Outcomes

Decrease in serum LDL-C and total cholesterol levels.