A statin - It lowers the level of cholesterol and triglycerides in the blood
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.
[Posted 08/08/2008] FDA notified healthcare professionals of the risk of muscle injury, rhabdomyolysis, which can lead to kidney failure or death, when simvastatin (Zocor) is used with amiodarone (Cordarone, Pacerone ). This risk is dose-related and increases when a dose of simvastatin greater than 20 mg per day is given with amiodarone. Although a revision of the simvastatin labeling in 2002 described an increased risk of rhabdomyolysis when amiodarone is taken with simvastatin doses greater than 20 mg daily, FDA continues to receive reports of rhabdomyolysis in patients treated concurrently with amiodarone and simvastatin. Prescribers should be aware of the increased risk of rhabdomyolysis when simvastatin is prescribed with amiodarone, and they should avoid doses of simvastatin greater than 20 mg per day in patients taking amiodarone. For more information visit the FDA website at: http://www.fda.gov/medwatch/safety/2008/safety08.htm#Simvastatin, http://www.fda.gov/cder/drug/infopage/simvastatin_amiodarone/default.htm, http://www.fda.gov/cder/drug/InfoSheets/HCP/simvastatin_amiodaroneHCP.htm, http://dailymed.nlm.nih.gov/dailymed/search.cfm?startswith=simvastatin and http://dailymed.nlm.nih.gov/dailymed/search.cfm?startswith=amiodarone&x=10&y=11.
Adjunct to dietary therapy in patients with CHD or CHD risk equivalents (e.g., diabetes mellitus, peripheral arterial disease, history of stroke or other cerebrovascular disease) to reduce the risk of total mortality by reducing CHD death, to reduce the risk of nonfatal MI and stroke, and to reduce the need for coronary and non-coronary revascularization procedures.
Slowing progression or inducing regression of atherosclerosis† in coronary arteries by reducing intimal-medial wall thickness.
Dyslipidemias
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.
Adjunct to dietary therapy in adults to decrease elevated serum total cholesterol, LDL-cholesterol, apolipoprotein B (apo B), and triglyceride concentrations and to increase HDL-cholesterol concentrations in the management of primary hypercholesterolemia and mixed dyslipidemia, including heterozygous familial hypercholesterolemia and other causes of hypercholesterolemia (e.g., polygenic hypercholesterolemia). May be used in combination or fixed combination with ezetimibe (as Vytorin® tablets) for additive antilipemic effects.
Adjunct to dietary therapy to decrease elevated serum total cholesterol, LDL-cholesterol, and apo B concentrations in the management of heterozygous familial hypercholesterolemia in boys and girls (≥1 year postmenarche) ≥10 years of age who have a serum LDL-cholesterol concentration of ≥190 mg/dL or in those who have a serum LDL-cholesterol concentration of ≥160 mg/dL and either a family history of premature cardiovascular disease or ≥2 cardiovascular risk factors despite an adequate trial of dietary management.
Reduction of elevated serum total and LDL-cholesterol concentrations in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering therapies (e.g., plasma LDL-apheresis) or when such therapies are not available. May be used in combination or fixed combination with ezetimibe (as Vytorin® tablets) for additive antilipemic effects.
Adjunct to dietary therapy to decrease elevated serum triglyceride concentrations in the management of hypertriglyceridemia.
Reduction of total and LDL-cholesterol concentrations in patients with hypercholesterolemia associated with or exacerbated by diabetes mellitus† (diabetic dyslipidemia), cardiac† or renal† transplantation, or nephrotic syndrome†.
Dosage and Administration
General
Patients should be placed on a standard lipid-lowering diet before initiation of simvastatin therapy and should remain on this diet during treatment with the drug; in patients with CHD or CHD risk equivalents, initiate simvastatin simultaneously with dietary management.
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
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.
Oral Administration
Administer orally in the evening without regard to meals.
Administer simvastatin-ezetimibe fixed-combination preparation (Vytorin®) 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
Oral
Children ≥10 years of age: 10 mg once daily.
Adjust dosage at intervals of ≥4 weeks until the desired effect on lipoprotein concentrations is observed. Usual dosage range is 10–40 mg daily.
Adults
Dyslipidemias and Prevention of Cardiovascular Events
Oral
Initially, 20–40 mg once daily.
Patients with CHD or CHD risk equivalents: Initially, 40 mg once daily.
Adjust dosage at intervals of no less than 4 weeks until the desired effect on lipoprotein concentrations is observed. Usual dosage range is 5–80 mg daily.
Simvastatin-ezetimibe fixed combination (Vytorin®): Initially, simvastatin 20 mg and ezetimibe 10 mg once daily in the evening. In patients requiring less aggressive LDL-cholesterol lowering, consider lower dosage (simvastatin 10 mg and ezetimibe 10 mg once daily). In patients requiring LDL-cholesterol reductions >55%, give simvastatin 40 mg and ezetimibe 10 mg once daily. Determine serum lipoprotein concentrations 2 weeks after initiation of therapy and adjust dosage as needed. Usual maintenance dosage is simvastatin 10–80 mg and ezetimibe 10 mg once daily.
Homozygous Familial Hypercholesterolemia
Oral
40 mg once daily in the evening or 80 mg daily in 3 divided doses of 20 mg, 20 mg, and an evening dose of 40 mg.
Simvastatin-ezetimibe fixed combination (Vytorin®): Initially, simvastatin 40 or 80 mg and ezetimibe 10 mg once daily in the evening.
Prescribing Limits
Pediatric Patients
Oral
Children ≥10 years of age: Maximum 40 mg once daily.
Special Populations
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.
Hepatic Impairment
Use with caution in patients who consume substantial amounts of alcohol and/or have a history of liver disease. Contraindicated in patients with active liver disease or unexplained, persistent increases in serum aminotransferase concentrations.
Renal Impairment
Dosage modification is not necessary in patients with mild to moderate impairment. In patients with severe renal impairment, initially, 5 mg once daily. Use with caution; monitor closely.
Simvastatin-ezetimibe fixed combination (Vytorin®): Dosage modification is not necessary in patients with mild to moderate impairment. In patients with severe renal impairment, do not use unless patient already has tolerated treatment with simvastatin at dosage of ≥5 mg daily; in such patients, exercise caution and monitor closely.
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