Ezetimibe

ezetimibe (ee zet' ah mib) Zetia Pregnancy Category C Drug classes

Cholesterol-lowering agent Cholesterol absorption inhibitor Therapeutic actions

Localizes in the brush border of the small intestine and inhibits the absorption of cholesterol from the small intestine; this leads to a decrease delivery of dietary cholesterol to the liver, which will then increase the clearance of cholesterol from the blood and lead to a decrease in serum cholesterol. Indications

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As an adjunct to diet and exercise to lower the cholesterol, LDL and Apo-B levels in patients with primary hypercholesterolemia as monotherapy or in combination with HMG-CoA reductase inhibitors (statins) or bile acid sequestrants In combination with atorvastatin or simvastatin for the treatment of homozygous familial hypercholesterolemia as adjuncts to other lipid-lowering treatments As adjunctive therapy to diet for the treatment of homozygous sitosterolemia to reduce elevated sitosterol and campesterol levels

Contraindications and cautions

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Contraindicated with allergy to any component of the drug. If given in combination with an HMG-CoA reductase inhibitor, contraindicated with pregnancy, lactation, active liver disease, or unexplained persistent increases in serum transaminase levels. In monotherapy, use cautiously with liver dysfunction, pregnancy, lactation, elderly patients.

Pharmacokinetics Route Oral

Onset Moderate

Peak 4–12 hr

Metabolism: Small intestine and hepatic; T1/2: 22 hr Distribution: May cross placenta; may enter into breast milk Excretion: Feces and urine Available forms

Tablets—10 mg Dosages ADULTS

10 mg/day PO taken without regard to food; may be taken at the same time as an HMGCoA reductase inhibitor; if combined with a bile acid sequestrant, should be taken > 2 hr before or > 4 hr after the bile acid sequestrant. PEDIATRIC PATIENTS

Safety and efficacy not established. Adverse effects

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CNS: Headache, dizziness, fatigue GI: Abdominal pain, diarrhea Respiratory: Pharyngitis, sinusitis, upper respiratory infection, cough Other: Back pain, myalgia, arthralgia, viral infection

Interactions

Drug-drug • Decreased serum levels and decreased effectiveness of ezetimibe if combined with cholestryamine; monitor patient closely and space ezetimibe dosing > 2 hr before or > 4 hr after the other drug • Increased serum levels of ezetimide if combined with fenofibrate, gemfibrozil • Risk of cholethiasis if combined with fibrates (concomitant use with fibrates not recommended) • Risk of increased levels and toxicity of exetimibe if combined with cyclosporine; if this combination is used; monitor patient very carefully Nursing considerations Assessment

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History: Allergy to any component of the drug; pregnancy, liver dysfunction, lactation, evidence of diet and exercise program Physical: Skin lesions, color, temperature; orientation, affect; liver evaluation, bowel sounds; lipid studies, liver function tests

Interventions

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Monitor serum cholesterol, LDLs, triglycerides before starting treatment and periodically during treatment. Determine that patient has been on low cholesterol diet and exercise program for at least 2 wk before starting ezetimibe. If used as part of combination therapy; give drug at the same time as HMG-CoA reductase inhibitors and > 2 hr before or > 4 hr after bile acid sequestrants. Encourage the use of barrier contraceptives if used with an HMG-CoA reductase inhibitor. Help mother to find another method of feeding her baby if this drug is needed for a nursing woman, it is not known if the drug enters breast milk. Consult with dietician regarding low cholesterol diets and provide information about exercise programs. Arrange for regular follow-up during long-term therapy.

Teaching points

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Take drug once each day at a time that is easy for you to remember. Do not take more than one tablet per day. Continue to take any other lipid-lowering drugs that have been prescribed for you. If you are also taking a bile acid sequestrant, take this drug at least 2 hr before or at least 4 hr after the bile sequestrant. Continue to follow your low-fat diet and participate in an exercise program. Plan to return for periodic blood tests, including tests of liver function and cholesterol levels, to evaluate the effectiveness of this drug. These side effects may occur: Abdominal pain, diarrhea (these usually pass with time, notify your health care provider if this becomes a problem); dizziness, (avoid driving and operating dangerous machinery until you know how this drug affects you); headache (analgesics may help). Report unusual muscle pain, weakness, or tenderness; severe diarrhea; respiratory infections.

Adverse effects in Italic are most common; those in Bold are life-threatening.