ZETIA (ezetimibe)

The information on this site is intended for healthcare professionals in the United States and is not intended for the general public.

I AM A HEALTHCARE PROFESSIONAL I AM NOT A HEALTHCARE PROFESSIONAL
 
Important Information About ZETIA
SIMVASTATIN – Illingworth 2001(4) A Titration Step Delivered LIMITED LDL-C Reduction
Examine Additional Statin Titration Studies
Click here for Study Design
bullet gif The effect of ZETIA on cardiovascular morbidity and mortality has not been determined.
bullet gif ZETIA, administered alone or in combination with an HMG-CoA reductase inhibitor (statin), 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 nonfamilial) hyperlipidemia when diet alone is not enough.
SELECTED CAUTIONARY INFORMATION
bullet gif ZETIA is not recommended in patients with moderate to severe hepatic impairment.
bullet gif The coadministration of ZETIA with fibrates other than fenofibrate is not recommended until use in patients is adequately studied.
bullet gif Exercise caution when using ZETIA and cyclosporine concomitantly because exposure to both drugs is increased. Cyclosporine concentrations should be monitored in these patients.
bullet gif ZETIA should be used in pregnant or nursing women only if the benefit outweighs the risk.
bullet gif In clinical trials, regardless of causality assessment, the most frequent side effects for ZETIA coadministered with a statin vs statin alone included nasopharyngitis (3.7% vs 3.3%), myalgia (3.2% vs 2.7%), upper respiratory tract infection (2.9% vs 2.8%), arthralgia (2.6% vs 2.4%), and diarrhea (2.5% vs 2.2%); for ZETIA administered alone vs placebo: upper respiratory tract infection (4.3% vs 2.5%), diarrhea (4.1% vs 3.7%), arthralgia (3.0% vs 2.2%), sinusitis (2.8% vs 2.2%), pain in extremity (2.7% vs 2.5%), and fatigue (2.4% vs 1.5%).

Before prescribing ZETIA, please read the Prescribing Information.

Important Information About VYTORIN
bullet gif VYTORIN contains 2 active ingredients: ezetimibe and simvastatin. No incremental benefit of VYTORIN on cardiovascular morbidity and mortality over and above that demonstrated for simvastatin has been established.
bullet gif VYTORIN is indicated as adjunctive therapy to diet for the reduction of elevated TOTAL-C, LDL-C, Apo B, TG, and non–HDL-C, and to increase HDL-C in patients with primary (heterozygous familial and nonfamilial) hyperlipidemia or mixed hyperlipidemia when diet alone is not enough.
bullet gif Contraindications: hypersensitivity to any component of this medication; active liver disease; unexplained persistent elevations in hepatic transaminase levels; and women who are pregnant, nursing, or may become pregnant.
SELECTED CAUTIONARY INFORMATION
bullet gif Skeletal Muscle: All patients starting therapy with VYTORIN, or whose dose of VYTORIN is being increased, should be advised of the risk of myopathy and told to promptly report any unexplained muscle pain, tenderness, or weakness. Therapy with VYTORIN should be discontinued immediately if myopathy is diagnosed or suspected.
bullet gif Myopathy and rhabdomyolysis are known adverse reactions to HMG-CoA reductase inhibitors and other lipid-lowering drugs. VYTORIN contains simvastatin, which occasionally causes myopathy manifested as muscle pain, tenderness, or weakness with CK levels above 10 × ULN. Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. Predisposing factors for myopathy include advanced age (≥65 years), uncontrolled hypothyroidism, and renal impairment. As with other statins, the risk of myopathy/rhabdomyolysis is dose related. VYTORIN should be discontinued immediately if myopathy is diagnosed or suspected. Please read WARNINGS in the Prescribing Information for additional information.
bullet gif Myopathy Caused by Drug Interactions: Use of VYTORIN with itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone, or large quantities of grapefruit juice (>1 quart daily) should be avoided because of the increased risk of myopathy, particularly at higher doses.
bullet gif The concomitant use of VYTORIN and fibrates (especially gemfibrozil) should be avoided. Although not recommended, the dose of VYTORIN should not exceed 10/10 mg if used with gemfibrozil.
bullet gif The benefit of further alterations in lipid levels by the combined use of VYTORIN with niacin (≥1 g/day) should be carefully weighed against the potential risks of myopathy. Chinese patients should not receive VYTORIN 10/80 mg daily with niacin (≥1 g/day). The dose of VYTORIN should not exceed 10/10 mg daily in patients receiving cyclosporine or danazol, 10/20 mg daily in patients receiving amiodarone or verapamil, and 10/40 mg daily in patients receiving diltiazem, due to the increased risk of myopathy. The combined use of VYTORIN at doses higher than 10/20 mg daily with amiodarone or verapamil or at doses higher than 10/40 mg daily with diltiazem should be avoided unless the clinical benefit is likely to outweigh the increased risk of myopathy.
bullet gif Liver: Due to the unknown effects of the increased exposure to ezetimibe in patients with moderate or severe hepatic impairment, VYTORIN is not recommended in these patients.
bullet gif The incidence of consecutive elevations (≥3 × ULN) in serum transaminases was 1.7% overall and appeared to be dose related, with an incidence of 2.6% for 10/80 mg. In long-term (48-week) extensions, which included both newly treated and previously treated patients, the incidence was 1.8% overall and 3.6% for 10/80 mg. These elevations were generally asymptomatic, not associated with cholestasis, and reversible whether treatment was maintained or discontinued.
bullet gif Liver function tests should be performed at treatment initiation and thereafter when clinically indicated. Patients titrated to 10/80 mg should receive an additional test prior to titration, 3 months after titration, and periodically thereafter (eg, semiannually) during the first year. If an increase in AST or ALT of ≥3 × ULN persists, discontinue the drug.
bullet gif In clinical trials, the most commonly reported side effects, regardless of cause, included headache (5.8%), increased ALT (3.7%), myalgia (3.6%), upper respiratory tract infection (3.6%), and diarrhea (2.8%).
SELECTED DOSAGE AND ADMINISTRATION INFORMATION
bullet gif VYTORIN is available as tablets containing 10 mg of ezetimibe combined with 10, 20, 40, or 80 mg of simvastatin (VYTORIN 10/10, 10/20, 10/40, or 10/80 mg, respectively).
bullet gif The recommended usual starting dose is 10/20 mg/day. Patients who require a larger reduction in LDL-C (greater than 55%) may be started at 10/40 mg/day. VYTORIN 10/10 mg may be considered for patients requiring less aggressive LDL-C reduction.
bullet gif No dosage adjustment is necessary in patients with mild or moderate renal impairment. Caution should be exercised when VYTORIN is administered to patients with severe renal insufficiency. VYTORIN should not be initiated in such patients unless the patient has already tolerated treatment with simvastatin.
Before prescribing VYTORIN, please read the Prescribing Information.
a

Study Design4: A 36-week, randomized, double-blind, parallel-group, dose-titration study in patients (N=826) with hypercholesterolemia with LDL-C >160 mg/dL and triglycerides <350 mg/dL randomized to receive either simvastatin 40 mg titrated to 80 mg at 6 weeks or atorvastatin 20 mg titrated every 6 weeks up to 80 mg. The primary end point was change from baseline in HDL-C averaged across the 2 dose comparisons in the initial 12 weeks. Mean baseline HDL-C and LDL-C levels were 50 mg/dL and 209 mg/dL for the simvastatin group and 51 mg/dL and 206 mg/dL for the atorvastatin group, respectively. Across Weeks 6 and 12, mean change from baseline in HDL-C was 9% with simvastatin vs 7% with atorvastatin (P<0.001).

After 6 weeks, mean LDL-C reduction from baseline was 46% with atorvastatin 20 mg vs 42% with simvastatin 40 mg (P≤0.001). After 12 weeks, mean LDL-C reduction from baseline was 51% with atorvastatin 40 mg vs 49% with simvastatin 80 mg (P≤0.001). After Weeks 18 to 36, mean LDL-C reduction from baseline was 54% with atorvastatin 80 mg vs 48% with simvastatin 80 mg (P≤0.001).

Additional LDL-C reduction provided by titration of atorvastatin 20 mg to 40 mg was 5% and from atorvastatin 40 mg to 80 mg was 3%. Additional LDL-C reduction provided by titration of simvastatin 40 mg to 80 mg was 6%.

The additional percent reductions in LDL-C with successive doses were obtained by subtraction from data presented.

Reference:
4. Illingworth DR, Crouse JR III, Hunninghake DB, et al. A comparison of simvastatin and atorvastatin up to maximal recommended doses in a large multicenter randomized clinical trial. Curr Med Res Opin. 2001;17:43–50.

This site is intended only for health care professionals of the United States, its territories, and Puerto Rico.

For non-US health care professionals, click here.

ZETIA and VYTORIN are registered trademarks of MSP Singapore Company, LLC.

Merck/Schering-Plough Pharmaceuticals        Merck/Schering-Plough Pharmaceuticals        Merck/Schering-Plough Pharmaceuticals
MerckMedicus™, MerckSource®, and MerckServices® are trademarks of Merck & Co., Inc.

Back to Top

21050228(1)-06/10-ZET