Drug Catalog - Product Detail
EZETIMIBE/SIMVASTATIN 10/40MG TB 90CT
| NDC | Mfr | Size | Str | Form |
|---|---|---|---|---|
| 45963-0567-08 | ACTAVIS | 90 | 10-40MG | TABLET |
PACKAGE FILES
Generic Name
EZETIMIBE AND SIMVASTATIN
Substance Name
EZETIMIBE
Product Type
HUMAN PRESCRIPTION DRUG
Route
ORAL
Application Number
ANDA202968
Description
11 DESCRIPTION Ezetimibe and Simvastatin Tablets contain ezetimibe USP, a selective inhibitor of intestinal cholesterol and related phytosterol absorption, and simvastatin USP, an HMG-CoA reductase inhibitor. The chemical name of ezetimibe, USP is 1-(4-fluorophenyl)-3(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)-(4-hydroxyphenyl)-2-azetidinone. The molecular formula is C 24 H 21 F 2 NO 3 and its molecular weight is 409.4. Ezetimibe, USP is a white, crystalline powder that is freely to very soluble in ethanol, methanol, and acetone and practically insoluble in water. Its structural formula is: Simvastatin, USP an inactive lactone, is hydrolyzed to the corresponding β-hydroxyacid form, which is an inhibitor of HMG-CoA reductase. Simvastatin, USP is butanoic acid, 2,2-dimethyl-,1,2,3,7,8,8a-hexahydro-3,7dimethyl-8-[2-(tetrahydro-4-hydroxy-6-oxo-2 H -pyran-2-yl)-ethyl]-1-naphthalenyl ester, [1 S -[1α,3α,7β,8β(2 S *,4 S *),-8aβ]]. The molecular formula of simvastatin, USP is C 25 H 38 O 5 and its molecular weight is 418.57. Simvastatin, USP is a white to off-white, nonhygroscopic, crystalline powder that is practically insoluble in water and freely soluble in chloroform, methanol and ethanol. Its structural formula is: Ezetimibe and simvastatin is available for oral use as tablets containing 10 mg of ezetimibe USP, and 10 mg of simvastatin, USP (ezetimibe and simvastatin tablets 10 mg/10 mg), 20 mg of simvastatin, USP (ezetimibe and simvastatin tablets 10 mg/20 mg), 40 mg of simvastatin, USP (ezetimibe and simvastatin tablets 10 mg/40 mg), or 80 mg of simvastatin, USP (ezetimibe and simvastatin tablets 10 mg/80 mg). Each tablet contains the following inactive ingredients: ascorbic acid, butylated hydroxyanisole, citric acid anhydrous, croscarmellose sodium, hypromellose, iron oxide black, iron oxide red, iron oxide yellow, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and propyl gallate. The structural formula of Ezetimibe is a white, crystalline powder that is freely to very soluble in ethanol, methanol, and acetone and practically insoluble in water. The structural formula of Simvastatin, USP is a white to off-white, nonhygroscopic, crystalline powder that is practically insoluble in water and freely soluble in chloroform, methanol and ethanol.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Ezetimibe and Simvastatin Tablets are supplied as follows: 10 mg/10 mg – Each light tan, slightly speckled, round, unscored, biconvex tablet debossed with 511 on one side and on opposite side contains 10 mg of ezetimibe, USP and 10 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-565-30), and 90 (NDC 45963-565-08). 10 mg/20 mg – Each light tan, slightly speckled, round, unscored, biconvex tablet debossed with 512 on one side and on opposite side contains 10 mg of ezetimibe, USP and 20 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-566-30), and 90 (NDC 45963-566-08). 10 mg/40 mg – Each light tan, slightly speckled, round, unscored, biconvex tablet debossed with 513 on one side and on opposite side contains 10 mg of ezetimibe, USP and 40 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-567-30), and 90 (NDC 45963-567-08). 10 mg/80 mg – Each light tan, slightly speckled, capsule shaped, unscored, biconvex tablet debossed with 515 on one side and on opposite side contains 10 mg of ezetimibe, USP and 80 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-568-30), and 90 (NDC 45963-568-08). Storage Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Keep container tightly closed. Dispense in a tight, light-resistant container as defined in the USP. 1 1 1 1
Indications & Usage
1 INDICATIONS AND USAGE Therapy with lipid-altering agents should be only one component of multiple risk factor intervention in individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Drug therapy is indicated as an adjunct to diet when the response to a diet restricted in saturated fat and cholesterol and other nonpharmacologic measures alone has been inadequate. Ezetimibe and simvastatin tablets, which contain a cholesterol absorption inhibitor and an HMG-CoA reductase inhibitor (statin), is indicated as adjunctive therapy to diet to: reduce elevated total-C, LDL-C, Apo B, TG, and non-HDL-C, and to increase HDL-C in patients with primary (heterozygous familial and non-familial) hyperlipidemia or mixed hyperlipidemia. ( 1.1 ) reduce elevated total-C and LDL-C in patients with homozygous familial hypercholesterolemia (HoFH), as an adjunct to other lipid-lowering treatments. ( 1.2 ) Limitations of Use ( 1.3 ) No incremental benefit of ezetimibe and simvastatin tablets on cardiovascular morbidity and mortality over and above that demonstrated for simvastatin has been established. Ezetimibe and simvastatin tablets have not been studied in Fredrickson Type I, III, IV, and V dyslipidemias. 1.1 Primary Hyperlipidemia Ezetimibe and simvastatin tablets are indicated for the reduction of elevated total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), triglycerides (TG), and non-high-density lipoprotein cholesterol (non-HDL-C), and to increase high-density lipoprotein cholesterol (HDL-C) in patients with primary (heterozygous familial and non-familial) hyperlipidemia or mixed hyperlipidemia. 1.2 Homozygous Familial Hypercholesterolemia (HoFH) Ezetimibe and simvastatin tablets are indicated for the reduction of elevated total-C and LDL-C in patients with homozygous familial hypercholesterolemia, as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable. 1.3 Limitations of Use No incremental benefit of ezetimibe and simvastatin tablets on cardiovascular morbidity and mortality over and above that demonstrated for simvastatin has been established. Ezetimibe and simvastatin tablets have not been studied in Fredrickson type I, III, IV, and V dyslipidemias.
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Dose range is 10 mg/10 mg/day to 10 mg/40 mg/day. ( 2.1 ) Recommended usual starting dose is 10 mg/10 mg or 10 mg/20 mg/day. ( 2.1 ) Due to the increased risk of myopathy, including rhabdomyolysis, use of the 10 mg/80-mg dose of ezetimibe and simvastatin should be restricted to patients who have been taking ezetimibe and simvastatin 10 mg/80 mg chronically (e.g., for 12 months or more) without evidence of muscle toxicity. ( 2.2 ) Patients who are currently tolerating the 10 mg/80-mg dose of ezetimibe and simvastatin who need to be initiated on an interacting drug that is contraindicated or is associated with a dose cap for simvastatin should be switched to an alternative statin or statin-based regimen with less potential for the drug-drug interaction. ( 2.2 ) Due to the increased risk of myopathy, including rhabdomyolysis, associated with the 10 mg/80-mg dose of ezetimibe and simvastatin, patients unable to achieve their LDL-C goal utilizing the 10 mg/40-mg dose of ezetimibe and simvastatin should not be titrated to the 10 mg/80-mg dose, but should be placed on alternative LDL-C-lowering treatment(s) that provides greater LDL-C lowering. ( 2.2 ) Dosing of ezetimibe and simvastatin should occur either greater than or equal to 2 hours before or greater than or equal to 4 hours after administration of a bile acid sequestrant. ( 2.3 , 7.5 ) 2.1 Recommended Dosing The usual dosage range is 10 mg/10 mg/day to 10 mg/40 mg/day. The recommended usual starting dose is 10 mg/10 mg/day or 10 mg/20 mg/day. Ezetimibe and simvastatin should be taken as a single daily dose in the evening, with or without food. Patients who require a larger reduction in LDL-C (greater than 55%) may be started at 10 mg/40 mg/day in the absence of moderate to severe renal impairment (estimated glomerular filtration rate less than 60 mL/min/1.73 m 2 ). After initiation or titration of ezetimibe and simvastatin, lipid levels may be analyzed after 2 or more weeks and dosage adjusted, if needed. 2.2 Restricted Dosing for 10 mg/ 80 mg Due to the increased risk of myopathy, including rhabdomyolysis, particularly during the first year of treatment, use of the 10 mg/80-mg dose of ezetimibe and simvastatin should be restricted to patients who have been taking ezetimibe and simvastatin 10 mg/80 mg chronically (e.g., for 12 months or more) without evidence of muscle toxicity [see Warnings and Precautions (5.1) ] . Patients who are currently tolerating the 10 mg/80-mg dose of ezetimibe and simvastatin who need to be initiated on an interacting drug that is contraindicated or is associated with a dose cap for simvastatin should be switched to an alternative statin or statin-based regimen with less potential for the drug-drug interaction. Due to the increased risk of myopathy, including rhabdomyolysis, associated with the 10 mg/80-mg dose of ezetimibe and simvastatin, patients unable to achieve their LDL-C goal utilizing the 10 mg/40-mg dose of ezetimibe and simvastatin should not be titrated to the 10 mg/80-mg dose, but should be placed on alternative LDL-C-lowering treatment(s) that provides greater LDL-C lowering. 2.3 Coadministration with Other Drugs Patients taking Verapamil, Diltiazem, or Dronedarone The dose of ezetimibe and simvastatin should not exceed 10 mg/10 mg/day [see Warnings and Precautions (5.1) , Drug Interactions (7.3) , and Clinical Pharmacology (12.3) ] . Patients taking Amiodarone, Amlodipine or Ranolazine The dose of ezetimibe and simvastatin should not exceed 10 mg/20 mg/day [see Warnings and Precautions (5.1) , Drug Interactions (7.3) , and Clinical Pharmacology (12.3) ] . Patients taking Bile Acid Sequestrants Dosing of ezetimibe and simvastatin should occur either greater than or equal to 2 hours before or greater than or equal to 4 hours after administration of a bile acid sequestrant [see Drug Interactions (7.5) ] . 2.4 Patients with Homozygous Familial Hypercholesterolemia The recommended dosage for patients with homozygous familial hypercholesterolemia is ezetimibe and simvastatin 10 mg/40 mg/day in the evening [see Dosage and Administration, Restricted Dosing for 10 mg/80 mg (2.2) ] . Ezetimibe and simvastatin should be used as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) in these patients or if such treatments are unavailable. Simvastatin exposure is approximately doubled with concomitant use of lomitapide; therefore, the dose of ezetimibe and simvastatin tablets should be reduced by 50% if initiating lomitapide. Ezetimibe and simvastatin tablets dosage should not exceed 10 mg/20 mg/day (or 10 mg/40 mg/day for patients who have previously taken simvastatin 80 mg/day chronically, e.g., for 12 months or more, without evidence of muscle toxicity) while taking lomitapide. 2.5 Patients with Renal Impairment/Chronic Kidney Disease In patients with mild renal impairment (estimated GFR greater than or equal to 60 mL/min/1.73 m 2 ), no dosage adjustment is necessary. In patients with chronic kidney disease and estimated glomerular filtration rate less than 60 mL/min/1.73 m 2 , the dose of ezetimibe and simvastatin is 10 mg/20 mg/day in the evening. In such patients, higher doses should be used with caution and close monitoring [see Warnings and Precautions (5.1) ; Clinical Pharmacology (12.3) ] . 2.6 Geriatric Patients No dosage adjustment is necessary in geriatric patients [see Clinical Pharmacology (12.3) ] .