INTEGRATED REVIEW Executive Summary Interdisciplinary Assessment Appendices NDA211617 Nexlizet I Bempedoic Acid and Ezetimibe
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Ezetimibe: a Novel Selective Cholesterol Absorption Inhibitor by Michele Koder, Pharm.D
OREGON DUR BOARD NEWSLETTER A N E VIDENCE B ASED D RUG T HERAPY R ESOURCE COPYRIGHT 2003 OREGON STATE UNIVERSITY. ALL RIGHTS RESERVED Volume 5, Issue 2 Also available on the web and via e-mail list-serve at February 2003 http://pharmacy.orst.edu/drug_policy/newsletter_email.html Ezetimibe: A novel selective cholesterol absorption inhibitor By Michele Koder, Pharm.D. , OSU College of Pharmacy Ezetimibe (Zetia) is a novel selective cholesterol absorption inhibitor that was approved by the FDA in October 2002. Unlike statins (HMG-CoA reductase inhibitors) and bile acid sequestrants, ezetimibe does not inhibit hepatic cholesterol synthesis or increase bile acid secretion. In contrast, ezetimibe selectively inhibits the uptake of dietary cholesterol from enterocytes in the brush border of the intestinal lumen resulting in a decrease in the delivery of dietary cholesterol to the liver and a subsequent decrease in hepatic cholesterol stores and increased cholesterol clearance from the blood.1 Ezetimibe’s unique action has generated interest in its use in combination with other cholesterol-lowering agents. It is indicated for the treatment of primary hypercholesterolemia as monotherapy and in combination with a statin. Ezetimibe is also approved for homozygous familial hypercholesterolemia and homozygous sitosterolemia. TABLE 1: EZETIMIBE CLINICAL TRIAL SUMMARY Study / Design Population Treatment % Change LDL % Change HDL % Change TG Bays et al3 N=432 EZ 5 mg -15.7 +2.9 MC, R, DB, PC LDL 130-250mg/dl EZ 10 mg -18.5 +3.5 NS 12 wk; Phase II TG -
A Novel Therapeutic Drug for the Treatment of Familial Hypercholesterolemia, Hyperlipidaemia, and Hypercholesterolemia
International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 8, Issue 3, 2016 Review Article MIPOMERSEN: A NOVEL THERAPEUTIC DRUG FOR THE TREATMENT OF FAMILIAL HYPERCHOLESTEROLEMIA, HYPERLIPIDAEMIA, AND HYPERCHOLESTEROLEMIA AJAY KUMAR1, ARUN ACHARYA2, DINOBANDHU NANDI3, NEHA SHARMA4, EKTA CHITKARA1* 1Department of Paramedical Sciences, Lovely Professional University, Phagwara-144411, Punjab (India) Email: [email protected] Received: 25 Dec 2015 Revised and Accepted: 13 Jan 2016 ABSTRACT Familial Hypercholesterolemia (FH) is one of the most common autosomal dominant disorders which exist in either heterozygous form or a homozygous form. These two forms are prevalent in 1 in 500 and 1 in a million population respectively. FH results in premature atherosclerosis; as early as childhood in case of homozygous (HoFH) form and in adults in case of heterozygous (HeFH) form. In case of HoFH both the alleles for LDL- receptor are defective, whereas the mutation in the single allele is the cause for HeFH. Both the forms of the disease are associated with high levels of LDL-C and lipoprotein (a) in plasma, with high morbidity and mortality rate caused by cardiovascular disease. In several past years, different lipid-lowering drugs like Statins (HMG-coenzyme-A reductase inhibitor), MTTP inhibitor, CETP inhibitors, PCSK9 inhibitor, thyroid mimetics, niacin, bile acid sequestrants and lipid apheresis were administered to patients with FH, to achieve the goal of reducing plasma LDL-C and lipoprotein (a). However, such drugs proved inefficient to achieve the goals because of several reasons. Mipomersen is a 20 nucleotide antisense oligonucleotide; a novel lipid-lowering therapeutic drug currently enrolled in the treatment of patients with HoFH, HeFH and other forms of hypercholesterolemia. -
Fenofibrate Ezetimibe Studies
FenofibrateFenofibrate EzetimibeEzetimibe SurrogateSurrogate TrialsTrials ThomasThomas Dayspring,Dayspring, MD,MD, FACPFACP Clinical Assistant Professor of Medicine University of Medicine and Dentistry of New Jersey Attending in Medicine: St Joseph’s Hospital, Paterson, NJ Certified Menopause Practitioner: North American Menopause Society North Jersey Institute of Menopausal Lipidology PharmacokineticPharmacokinetic DataData FenofibrateFenofibrate –– EzetimibeEzetimibe PharmacodynamicPharmacodynamic andand PharmacokineticPharmacokinetic InteractionInteraction StudyStudy Placebo (n = 8) Ezetimibe 10 mg (n = 8) Patients have no physical 30 activity and are on a high Fenofibrate 200 mg (n = 8) carbohydrate low fat diet which lowers HDL-C 20 Fenofibrate 200mg + 10 Ezetimibe 10 mg (n = 8) 0 -10 -20 -30 Change from Baseline (%) -40 -50 TC LDL-C HDL-C TG Mean (SE) percentage change from baseline in serum lipids on day 14 following oral administration of fenofibrate monotherapy, ezetimibe monotherapy, fenofibrate-ezetimibe co- administration therapy or placebo once daily to 14 healthy subjects with hypercholesterolemia Kosoglou T et al. Curr Med Res & Opin 2004;20:1185-1195 FenofibrateFenofibrate –– EzetimibeEzetimibe PharmacodynamicPharmacodynamic andand PharmacokineticPharmacokinetic InteractionInteraction StudyStudy Placebo (n = 8) 30 Ezetimibe 10 mg (n = 8) Fenofibrate 200 mg (n = 8) Combination therapy 20 produced significantly Fenofibrate 200mg + 10 Ezetimibe 10 mg (n = 8) greater reductions in 0 LDL-C and in small LDL-III -10 Levels of -
SUMMARY of the PRODUCT CHARACTERISTICS 1. NAME of the MEDICINAL PRODUCT <Invented Name> 10 Mg/10 Mg Film-Coated Tablets
SUMMARY OF THE PRODUCT CHARACTERISTICS 1. NAME OF THE MEDICINAL PRODUCT <Invented name> 10 mg/10 mg film-coated tablets <Invented name> 20 mg/10 mg film-coated tablets <Invented name> 40 mg/10 mg film-coated tablets 2. QUALITATIVE AND QUANTITATIVE COMPOSITION <Invented name> 10 mg/10 mg: Each film-coated tablet contains 10 mg of rosuvastatin (as rosuvastatin calcium) and 10 mg of ezetimibe. <Invented name> 20 mg/10 mg: Each film-coated tablet contains 20 mg of rosuvastatin (as rosuvastatin calcium) and 10 mg of ezetimibe. <Invented name> 40 mg/10 mg: Each film-coated tablet contains 40 mg of rosuvastatin (as rosuvastatin calcium) and 10 mg of ezetimibe. Excipient with known effect: <Invented name> 10 mg/10 mg: Each film-coated tablet contains 111.2 mg of lactose (as lactose monohydrate). <Invented name> 20 mg/10 mg: Each film-coated tablet contains 168.6 mg of lactose (as lactose monohydrate). <Invented name> 40 mg/10 mg: Each film-coated tablet contains 286.0 mg of lactose (as lactose monohydrate). For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Film-coated tablet (tablet) <Invented name> 10 mg/10 mg: white to off-white oblong film-coated tablets. <Invented name> 20 mg/10 mg: yellow to light yellow oblong film-coated tablets. <Invented name> 40 mg/10 mg: pink oblong film-coated tablets. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Primary Hypercholesterolaemia/Homozygous Familial Hypercholesterolaemia (HoFH) <Invented name> is indicated for substitution therapy in adult patients who are adequately controlled with rosuvastatin and ezetimibe given concurrently at the same dose level as in the fixed combination, but as separate products, as adjunct to diet for treatment of primary hypercholesterolaemia (heterozygous familial and non-familial) or homozygous familial hypercholesterolaemia. -
Zetia® (Ezetimibe) Tablets
29480958T REV 14 ZETIA® (EZETIMIBE) TABLETS DESCRIPTION ZETIA (ezetimibe) is in a class of lipid-lowering compounds that selectively inhibits the intestinal absorption of cholesterol and related phytosterols. The chemical name of ezetimibe is 1-(4-fluorophenyl)- 3(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)-(4-hydroxyphenyl)-2-azetidinone. The empirical formula is C24H21F2NO3. Its molecular weight is 409.4 and its structural formula is: OH OH S SR N F F O Ezetimibe is a white, crystalline powder that is freely to very soluble in ethanol, methanol, and acetone and practically insoluble in water. Ezetimibe has a melting point of about 163°C and is stable at ambient temperature. ZETIA is available as a tablet for oral administration containing 10 mg of ezetimibe and the following inactive ingredients: croscarmellose sodium NF, lactose monohydrate NF, magnesium stearate NF, microcrystalline cellulose NF, povidone USP, and sodium lauryl sulfate NF. CLINICAL PHARMACOLOGY Background Clinical studies have demonstrated that elevated levels of total cholesterol (total-C), low density lipoprotein cholesterol (LDL-C) and apolipoprotein B (Apo B), the major protein constituent of LDL, promote human atherosclerosis. In addition, decreased levels of high density lipoprotein cholesterol (HDL-C) are associated with the development of atherosclerosis. Epidemiologic studies have established that cardiovascular morbidity and mortality vary directly with the level of total-C and LDL-C and inversely with the level of HDL-C. Like LDL, cholesterol-enriched triglyceride-rich lipoproteins, including very-low- density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), and remnants, can also promote atherosclerosis. The independent effect of raising HDL-C or lowering triglycerides (TG) on the risk of coronary and cardiovascular morbidity and mortality has not been determined. -
Volanesorsen Fdaadvisory Committee Meeting Briefing Document
VOLANESORSEN FDA ADVISORY COMMITTEE MEETING BRIEFING DOCUMENT ENDOCRINE AND METABOLIC DRUGS ADVISORY COMMITTEE MEETING DATE: 10 MAY 2018 ADVISORY COMMITTEE BRIEFING MATERIALS: AVAILABLE FOR PUBLIC RELEASE Volanesorsen (ISIS 304801) Akcea Therapeutics Endocrine and Metabolic Drugs Advisory Committee Briefing Document 10 May 2018 Meeting TABLE OF CONTENTS TABLE OF CONTENTS .................................................................................................................2 TABLE OF TABLES ......................................................................................................................6 TABLE OF FIGURES .....................................................................................................................9 LIST OF ABBREVIATIONS ........................................................................................................10 1. EXECUTIVE SUMMARY ........................................................................................11 1.1 Familial Chylomicronemia Syndrome ........................................................................12 1.1.1 Overview of the Disease and Impact of Elevated Triglyceride Levels ......................12 1.1.2 Current Treatment Options .........................................................................................14 1.2 Volanesorsen Clinical Development Program ............................................................15 1.3 Efficacy and Safety of Volanesorsen ..........................................................................15 -
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Ehealth DSI [Ehdsi V2.2.2-OR] Ehealth DSI – Master Value Set
MTC eHealth DSI [eHDSI v2.2.2-OR] eHealth DSI – Master Value Set Catalogue Responsible : eHDSI Solution Provider PublishDate : Wed Nov 08 16:16:10 CET 2017 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 1 of 490 MTC Table of Contents epSOSActiveIngredient 4 epSOSAdministrativeGender 148 epSOSAdverseEventType 149 epSOSAllergenNoDrugs 150 epSOSBloodGroup 155 epSOSBloodPressure 156 epSOSCodeNoMedication 157 epSOSCodeProb 158 epSOSConfidentiality 159 epSOSCountry 160 epSOSDisplayLabel 167 epSOSDocumentCode 170 epSOSDoseForm 171 epSOSHealthcareProfessionalRoles 184 epSOSIllnessesandDisorders 186 epSOSLanguage 448 epSOSMedicalDevices 458 epSOSNullFavor 461 epSOSPackage 462 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 2 of 490 MTC epSOSPersonalRelationship 464 epSOSPregnancyInformation 466 epSOSProcedures 467 epSOSReactionAllergy 470 epSOSResolutionOutcome 472 epSOSRoleClass 473 epSOSRouteofAdministration 474 epSOSSections 477 epSOSSeverity 478 epSOSSocialHistory 479 epSOSStatusCode 480 epSOSSubstitutionCode 481 epSOSTelecomAddress 482 epSOSTimingEvent 483 epSOSUnits 484 epSOSUnknownInformation 487 epSOSVaccine 488 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 3 of 490 MTC epSOSActiveIngredient epSOSActiveIngredient Value Set ID 1.3.6.1.4.1.12559.11.10.1.3.1.42.24 TRANSLATIONS Code System ID Code System Version Concept Code Description (FSN) 2.16.840.1.113883.6.73 2017-01 A ALIMENTARY TRACT AND METABOLISM 2.16.840.1.113883.6.73 2017-01 -
Efficacy of Combination Therapy of Rosuvastatin and Ezetimibe Vs
Original Article DOI: 10.7860/JCDR/2017/30458.11004 Efficacy of Combination Therapy Internal Medicine Section of Rosuvastatin and Ezetimibe vs Rosuvastatin Monotherapy on Lipid Profile of Patients with Coronary Artery Disease SANDEEP JOSHI1, RUBY SHARMA2, HARBIR KAUR RAO3, UDIT NARANG4, NITIN GUPTA5 ABSTRACT baseline investigations and lifestyle modifications, Group I Introduction: Dyslipidaemia is one of the most important was started on rosuvastatin 10 mg once daily, while Group modifiable risk factor for the development of Coronary II was started on rosuvastatin 10 mg+ezetimibe 10 mg daily. Artery Disease (CAD). Although, statins are established as The fasting serum lipid profile was repeated initially after first line lipid-lowering therapy, they may not be able to 12 weeks and then after 24 weeks. The two groups were achieve treatment goals in significant number of patients. observed for side effects which were noted. Combination therapy of statin with a non-statin drug like Results: The combination therapy of rosuvastatin and Ezetimibe is a therapeutic option. ezetimibe resulted in significantly higher change in all Aim: To compare the efficacy and safety of Rosuvastatin/ lipid parameters (LDL-C, TC, TG, HDL-C) as compared to Ezetimibe combination therapy vs Rosuvastatin alone on the treatment with rosuvastatin alone. There was no difference in lipid profile of patients with CAD in Northern India. the adverse effects seen after treatment in the two groups. Materials and Methods: This randomized prospective Conclusion: Our study showed that combination therapy study was conducted on 80 patients of CAD presenting of ezetimibe with rosuvastatin can be used as an effective to Department of Medicine, Government Medical College, and safe therapy in high risk patients of CAD, especially in Patiala, Punjab, India. -
Annexes of the Annual Report 2011
1 June 2012 EMA/363033/2012 Office of the Executive Director Annexes of the annual report 2011 The main body of this report is available on the website of the European Medicines Agency (EMA) here. 7 Westferry Circus ● Canary Wharf ● London E14 4HB ● United Kingdom Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7418 8416 E-mail [email protected] Website www.ema.europa.eu An agency of the European Union © European Medicines Agency, 2012. Reproduction is authorised provided the source is acknowledged. Table of contents Annex 1 – Members of the Management Board ................................................... 3 Annex 2 – Members of the Committee for Medicinal Products for Human Use ......... 5 Annex 3 – Members of the Committee for Medicinal Products for Veterinary Use .... 9 Annex 4 – Members of the Committee for Orphan Medicinal Products.................. 11 Annex 5 – Members of the Committee on Herbal Medicinal Products ................... 13 Annex 6 – Members of the Paediatric Committee .............................................. 16 Annex 7 – Members of the Committee for Advanced Therapies ........................... 18 Annex 8 – National competent authority partners ............................................. 20 Annex 9 – Budget summaries 2010–2011........................................................ 31 Annex 10 – Establishment plan ...................................................................... 32 Annex 11 – CHMP opinions in 2011 on medicinal products for human use ............ 33 Annex 12 – CVMP opinions in 2011 -
CP.PMN.237 Bempedoic Acid (Nexletol)
Clinical Policy: Bempedoic Acid (Nexletol), Bempedoic Acid/Ezetimibe (Nexlizet) Reference Number: CP.PMN.237 Effective Date: 09.01.20 Last Review Date: 02.21 Revision Log Line of Business: Commercial, HIM, Medicaid See Important Reminder at the end of this policy for important regulatory and legal information. Description The following are adenosine triphosphate-citrate lyase (ACL) inhibitors requiring prior authorization: bempedoic acid (Nexletol™) and bempedoic acid/ezetimibe (Nexlizet™). Nexlizet contains ezetimibe, which is a cholesterol absorption inhibitor. FDA Approved Indication(s) Nexletol and Nexlizet are indicated for use as adjuncts to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or established atherosclerotic cardiovascular disease (ASCVD) who require additional lowering of low-density lipoprotein cholesterol (LDL-C). Limitation(s) of use: The effect of Nexletol and Nexlizet on cardiovascular morbidity and mortality has not been determined. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria. It is the policy of health plans affiliated with Centene Corporation® that Nexletol and Nexlizet are medically necessary when the following criteria are met: I. Initial Approval Criteria A. Heterozygous Familial Hypercholesterolemia and Atherosclerotic Cardiovascular Disease (must meet all): 1. Diagnosis of one of the following (a or b): a. ASCVD as evidenced by a history of any one of the following conditions (i-vii): i. Acute coronary syndromes; ii. Clinically significant coronary heart disease (CHD) diagnosed by invasive or noninvasive testing (such as coronary angiography, stress test using treadmill, stress echocardiography, or nuclear imaging); iii. -
Mipomersen (KYNAMRO®) Monograph
Mipomersen (KYNAMRO®) Monograph Mipomersen (KYNAMRO®) National Drug Monograph May 2015 VA Pharmacy Benefits Management Services, Medical Advisory Panel, and VISN Pharmacist Executives The purpose of VA PBM Services drug monographs is to provide a focused drug review for making formulary decisions. Updates will be made when new clinical data warrant additional formulary discussion. Documents will be placed in the Archive section when the information is deemed to be no longer current. FDA Approval Information1 Description/Mechanism of Mipomersen (KYNAMRO) is the first-in-class antisense oligonucleotide Action (ASO) inhibitor directed at inhibiting the production of human apolipoprotein B-100 (ApoB). Apoliprotein B is the major structural lipoprotein of very low- density lipoprotein cholesterol (VLDL-C). Reduced availability of ApoB results in reduced production of VLDL in the liver and therefore less VLDL is released into the circulation. Reduced VLDL results in lower levels of low-density lipoprotein cholesterol (LDL-C) and other lipoproteins. Additionally, VLDL transports triglycerides (TGs) from the liver into the circulation. Therefore, lower levels of VLDL results in accumulation of TGs in the liver. Indication(s) Under Review in Mipomersen is approved as an adjunct to lipid-lowering medications and diet to this document (may include reduce LDL-C, ApoB, total cholesterol (TC) and non-high density lipoprotein off label) cholesterol (HDL-C) in patients with homozygous familial hypercholesterolemia (HoFH). The safety and effectiveness of mipomersen has not been established in patients with hypercholesterolemia who do not have HoFH. The safety and effectiveness of mipomersen as an adjunct to LDL apheresis is unknown; and therefore the treatment combination is not recommended. -
Information for the User Ezetimibe/Simvastatin Clonmel 10 Mg/10 Mg Tablets Ezetimibe/Simvastatin Clonmel 10 Mg
Package leaflet: Information for the user Ezetimibe/Simvastatin Clonmel 10 mg/10 mg tablets Ezetimibe/Simvastatin Clonmel 10 mg/20 mg tablets Ezetimibe/Simvastatin Clonmel 10 mg/40 mg tablets Ezetimibe/Simvastatin Clonmel 10 mg/80 mg tablets Ezetimibe/simvastatin Read all of this leaflet carefully before you start using this medicine because it contains important information for you. - Keep this leaflet. You may need to read it again. - If you have any further questions, ask your doctor or pharmacist. - This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours. - If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4. What is in this leaflet 1. What Ezetimibe/Simvastatin Clonmel is and what it is used for 2. What you need to know before you take Ezetimibe/Simvastatin Clonmel 3. How to take Ezetimibe/Simvastatin Clonmel 4. Possible side effects 5. How to store Ezetimibe/Simvastatin Clonmel 6. Contents of the pack and other information 1. What Ezetimibe/Simvastatin Clonmel is and what it is used for Ezetimibe/Simvastatin Clonmel is a medicine used to lower levels of total cholesterol, “bad” cholesterol (LDL cholesterol), and fatty substances called triglycerides in the blood. In addition, Ezetimibe/Simvastatin Clonmel raises levels of “good” cholesterol (HDL cholesterol). Ezetimibe/Simvastatin Clonmel contains the active substances ezetimibe and simvastatin. Ezetimibe/Simvastatin Clonmel works to reduce your cholesterol in two ways.