A cholesterol absorption inhibitor - It can help lower blood cholesterol for patients who are at ris... more
FDA Alerts
Special Alerts:
[Posted 08/21/2008] FDA informed healthcare professionals that the Agency is investigating a report from the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial of a possible association between the use of ezetimibe with simvastatin (Vytorin) and a potentially increased incidence of cancer. Vytorin is a combination product of simvastatin and ezetimibe used to decrease the production of cholesterol by the liver and inhibit the absorption of cholesterol in the intestine to reduce LDL-cholesterol levels and reduce the risk of cardiovascular events. Recently, FDA obtained preliminary results from the SEAS trial. The clinical trial tested whether lowering LDL-cholesterol with Vytorin would reduce the risk of cardiovascular events in individuals with aortic stenosis. A lower overall cardiovascular risk was not found with Vytorin. However, there was an additional observation that a larger percentage of subjects treated with Vytorin were diagnosed with and died from all types of cancer combined when compared to placebo during the 5-year study.
FDA anticipates receiving a final SEAS study report in about 3 months and the Agency's review and evaluation of the clinical trial data and other relevant information should take approximately 6 months. FDA will communicate its conclusions and recommendations at that time. Healthcare professionals and caregivers should continue to monitor patients taking Vytorin and report side effects from the use of this drug to the Agency. For more information visit the FDA website at: http://www.fda.gov/medwatch/safety/2008/safety08.htm#ezetimibe2 and http://www.fda.gov/cder/drug/early_comm/ezetimibe_simvastatin_SEAS.htm.
Pending revision, the material in this section should be considered in light of more recently available information in the MEDWATCH notification at the beginning of this monograph.
Primary Hypercholesterolemia and Mixed Dyslipidemia
Use alone or in combination with a hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) as an adjunct to dietary therapy to decrease elevated serum total cholesterol, LDL-cholesterol, and apolipoprotein B (apo B) concentrations in the treatment of primary (heterozygous familial and nonfamilial) hypercholesterolemia. Effects on cardiovascular morbidity and mortality not established.
Use in fixed combination with simvastatin (i.e., Vytorin®) as an adjunct to dietary therapy to decrease elevated serum total cholesterol, LDL-cholesterol, apo B, triglyceride, and non-HDL-cholesterol concentrations, and to increase HDL-cholesterol concentrations in the treatment of primary hypercholesterolemia or mixed dyslipidemia.
Use in combination with fenofibrate as an adjunct to dietary therapy to decrease elevated serum total cholesterol, LDL-cholesterol, apo B, and non-HDL-cholesterol concentrations in the treatment of mixed dyslipidemia. Effects on cardiovascular morbidity and mortality not established. Use with a fibric acid derivative other than fenofibrate not studied and currently not recommended. (See Specific Drugs under Interactions.)
Produces negligible increases in HDL-cholesterol concentrations.
Drug therapy is not a substitute for but an adjunct to nondrug therapies and measures (e.g., dietary management, weight control, physical activity, management of potentially contributory disease), which should be continued when drug therapy is initiated.
Homozygous Familial Hypercholesterolemia
Use in combination with atorvastatin or simvastatin to decrease elevated serum total and LDL-cholesterol concentrations in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering therapies (e.g., plasma LDLapheresis) or when such therapies are not available.
Effects in patients currently undergoing LDL apheresis compared with those in patients not undergoing the procedure not established. Effects on clinical outcome and modification of other disease parameters (e.g., xanthoma formation, regression of atherosclerosis) not established.
Adjunct to dietary therapy to decrease elevated serum sitosterol and campesterol concentrations in patients with homozygous familial sitosterolemia.
Reductions in sitosterol and campesterol concentrations were consistent between patients receiving ezetimibe with or without bile acid sequestrants.
Effect of reducing plasma concentrations of sitosterol and campesterol on cardiovascular morbidity and mortality not established.
Dosage and Administration
General
Patients should be placed on a standard cholesterol-lowering diet before initiation of ezetimibe therapy and should remain on this diet during treatment with the drug.
Monitoring during Antilipemic Therapy
Monitor lipoprotein concentrations periodically to ensure that target LDL-cholesterol goals are achieved and maintained at <100 mg/dL (optional goal: <70 mg/dL) for patients with CHD or CHD risk equivalents; <130 mg/dL (optional goal: <100 mg/dL) for patients with ≥2 risk factors and 10-year risk of 10–20%; <130 mg/dL for patients with ≥2 risk factors and 10-year risk <10%; or <160 mg/dL for patients with 0–1 risk factor.
Administration
Oral Administration
Administer orally without regard to meals.
Combination therapy with a statin or fenofibrate: May administer ezetimibe at same time as the statin or fenofibrate, in accordance with recommended dosing schedule for these drugs.
Combination therapy with a bile acid sequestrant: Administer ≥2 hours before or ≥4 hours after bile acid sequestrant.
Ezetimibe/simvastatin fixed-combination preparation: Administer orally in the evening without regard to meals.
Dosage
Pending revision, the material in this section should be considered in light of more recently available information in the MEDWATCH notification at the beginning of this monograph.
Pediatric Patients
Dyslipidemias
Primary Hypercholesterolemia and Mixed Dyslipidemia
Oral
Children ≥10 years of age: 10 mg once daily.
Homozygous Familial Hypercholesterolemia
Oral
Children ≥10 years of age: 10 mg once daily.
Homozygous Familial Sitosterolemia
Oral
Children ≥10 years of age: 10 mg once daily.
Adults
Pending revision, the material in this section should be considered in light of more recently available information in the MEDWATCH notification at the beginning of this monograph.
Dyslipidemias
Primary Hypercholesterolemia and Mixed Dyslipidemia
Oral
10 mg once daily.
Ezetimibe/simvastatin fixed combination (Vytorin®): Initially, ezetimibe 10 mg/simvastatin 20 mg once daily in the evening. In patients requiring less aggressive LDL-cholesterol lowering, consider dosage of ezetimibe 10 mg/simvastatin 10 mg once daily. In patients requiring LDL-cholesterol reductions ≥55%, may initiate therapy with ezetimibe 10 mg/simvastatin 40 mg once daily. Determine serum cholesterol concentrations ≥2 weeks after initiation of therapy and adjust dosage as needed. Usual maintenance dosage range is ezetimibe 10 mg and simvastatin 10–80 mg once daily.
Homozygous Familial Hypercholesterolemia
Oral
10 mg once daily.
Ezetimibe/simvastatin fixed combination (Vytorin®): Ezetimibe 10 mg/simvastatin 40 mg or ezetimibe 10 mg/simvastatin 80 mg once daily in the evening. Use as adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable.
Homozygous Familial Sitosterolemia
Oral
10 mg once daily.
Special Populations
Hepatic Impairment
Ezetimibe
No dosage adjustment needed in patients with mild hepatic impairment. Do not use in patients with moderate or severe hepatic impairment.
Ezetimibe/Simvastatin Fixed Combination
No dosage adjustment needed in patients with mild hepatic impairment. Do not use in patients with moderate or severe hepatic impairment.
Renal Impairment
Ezetimibe
No dosage adjustment needed in patients with renal impairment.
Ezetimibe/Simvastatin Fixed Combination
No dosage adjustment needed in patients with mild to moderate renal impairment. Do not use in patients with severe renal impairment unless patient has already tolerated treatment with a simvastatin dosage ≥5 mg daily; in such patients, exercise caution and monitor closely.
Geriatric Patients
Ezetimibe
No dosage adjustment needed in geriatric patients (≥65 years of age).
Ezetimibe/Simvastatin Fixed Combination
No dosage adjustment needed in geriatric patients (≥65 years of age).
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