INDICATIONS AND USAGE
Primary Hypercholesterolemia Monotherapy
ZETIA, administered alone, is indicated as adjunctive therapy to diet for the reduction of elevated total-C, LDL-C, and Apo B in patients with primary (heterozygous familial and non-familial) hypercholesterolemia.
Combination therapy with HMG-CoA reductase inhibitors
ZETIA, administered in combination with an HMG-CoA reductase inhibitor, is indicated as adjunctive therapy to diet for the reduction of elevated total-C, LDL-C, and Apo B in patients with primary (heterozygous familial and non-familial) hypercholesterolemia.
Homozygous Familial Hypercholesterolemia (HoFH)
The combination of ZETIA and atorvastatin or simvastatin, is indicated for the reduction of elevated total-C and LDL-C levels in patients with HoFH, as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable. Homozygous Sitosterolemia
ZETIA is indicated as adjunctive therapy to diet for the reduction of elevated sitosterol and campesterol levels in patients with homozygous familial sitosterolemia.
Therapy with lipid-altering agents should be a component of multiple risk-factor intervention in individuals at increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Lipid-altering agents should be used in addition to an appropriate diet (including restriction of saturated fat and cholesterol) and when the response to diet and other non-pharmacological measures has been inadequate. (See NCEP Adult Treatment Panel (ATP) III Guidelines, summarized in Table 7.)
Table 7 Summary of NCEP ATP III Guidelines
| Risk Category |
LDL Goal (mg/dL) |
LDL Level at Which to Initiate
Therapeutic Lifestyle Changes a (mg/dL) |
LDL level at Which to
Consider Drug Therapy (mg/dL) |
|
|
CHD or CHD risk
equivalents b
(10-year risk >20%) c |
<100
|
>/=100
|
>/=130
(100-129: drug optional) d |
2+ Risk factors e
(10-year risk c |
<130
|
>/=130
|
10-year risk 10-20%: >/=130 c
10-year risk <10%: >/=160 c |
|
0-1 Risk factor f |
<160
|
>/=160
|
>/=190
(160-189: LDL-lowering drug optional) |
| a Therapeutic lifestyle changes include: 1) dietary changes: reduced intake of saturated fats (<7% of total calories) and cholesterol (<200 mg per day), and enhancing LDL lowering with plant stanols/sterols (2 g/d) and increased viscous (soluble) fiber (10-25 g/d), 2) weight reduction, and 3) increased physical activity.
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| b CHD risk equivalents comprise: diabetes, multiple risk factors that confer a 10-year risk for CHD >20%, and other clinical forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm and symptomatic carotid artery disease).
|
| c Risk assessment for determining the 10-year risk for developing CHD is carried out using the Framingham risk scoring. Refer to JAMA, May 16, 2001; 285 (19): 2486-2497, or the NCEP website (http://www.nhlbi.nih.gov) for more details. |
| d Some authorities recommend use of LDL-lowering drugs in this category if an LDL cholesterol <100 mg/dL cannot be achieved by therapeutic lifestyle changes. Others prefer use of drugs that primarily modify triglycerides and HDL, e.g., nicotinic acid or fibrate. Clinical judgment also may call for deferring drug therapy in this subcategory. |
| e Major risk factors (exclusive of LDL cholesterol) that modify LDL goals include cigarette smoking, hypertension (BP >/=140/90 mm Hg or on anti-hypertensive medication), low HDL cholesterol (<40 mg/dL), family history of premature CHD (CHD in male first-degree relative <55 years; CHD in female first-degree relative <65 years), age (men >/=45 years; women >/=55 years). HDL cholesterol >/=60 mg/dL counts as a "negative" risk factor; its presence removes one risk factor from the total count.
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| f Almost all people with 0-1 risk factor have a 10-year risk <10%; thus, 10-year risk assessment in people with 0-1 risk factor is not necessary. |
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Prior to initiating therapy with ZETIA, secondary causes for dyslipidemia (i.e., diabetes, hypothyroidism, obstructive liver disease, chronic renal failure, and drugs that increase LDL-C and decrease HDL-C [progestins, anabolic steroids, and corticosteroids]), should be excluded or, if appropriate, treated. A lipid profile should be performed to measure total-C, LDL-C, HDL-C and TG. For TG levels >400 mg/dL (>4.5 mmol/L), LDL-C concentrations should be determined by ultracentrifugation.
At the time of hospitalization for an acute coronary event, lipid measures should be taken on admission or within 24 hours. These values can guide the physician on initiation of LDL-lowering therapy before or at discharge.
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DOSAGE AND ADMINISTRATION
The patient should be placed on a standard cholesterol-lowering diet before receiving ZETIA and should continue on this diet during treatment with ZETIA.
The recommended dose of ZETIA is 10 mg once daily. ZETIA can be administered with or without food.
ZETIA may be administered with an HMG-CoA reductase inhibitor for incremental effect. For convenience, the daily dose of ZETIA may be taken at the same time as the HMG-CoA reductase inhibitor, according to the dosing recommendations for the HMG-CoA reductase inhibitor.
PATIENTS WITH HEPATIC INSUFFICIENCY
No dosage adjustment is necessary in patients with mild hepatic insufficiency (see PRECAUTIONS, Hepatic Insufficiency).
Patients with Renal Insufficiency
No dosage adjustment is necessary in patients with renal insufficiency (see CLINICAL PHARMACOLOGY, Special Populations).
Geriatric Patients
No dosage adjustment is necessary in geriatric patients (see CLINICAL PHARMACOLOGY, Special Populations).
Co-administration with Bile Acid Sequestrants
Dosing of ZETIA should occur either >/=2 hours before or >/=4 hours after administration of a bile acid sequestrant (see PRECAUTIONS, Drug Interactions).
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HOW SUPPLIED
No. 3861 - Tablets ZETIA, 10 mg, are white to off-white, capsule-shaped tablets debossed with "414" on one side. They are supplied as follows: NDC 66582-414-31 bottles of 30
NDC 66582-414-54 bottles of 90
NDC 66582-414-74 bottles of 500
NDC 66582-414-28 unit dose packages of 100. Storage
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F). [See USP Controlled Room Temperature.] Protect from moisture.
25751868T
REV 04
Issued August 2004
Printed in USA.
Manufactured for:
Merck/Schering-Plough Pharmaceuticals
North Wales, PA 19454, USA
By:
Schering Corporation
Kenilworth, NJ 07033, USA
or
Merck & Co., Inc.
Whitehouse Station, NJ 08889, USA
COPYRIGHT © Merck/Schering-Plough Pharmaceuticals, 2001, 2002, All rights reserved.
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