DOCSLIB.ORG

Therapeutic Class Overview Bile Acid Sequestrants

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Therapeutic Class Overview Bile Acid Sequestrants Therapeutic Class Overview Bile Acid Sequestrants Therapeutic Class • Overview/Summary: The major action of the bile acid sequestrants in modifying lipids is through binding to bile acids in the intestine causing an interruption of their reabsorption. This reduction leads to feedback regulation to increase the conversion of cholesterol to bile acids. The major action of these agents is to reduce low density lipoprotein cholesterol (LDL-C) specifically; therefore, use of a bile acid sequestrant is effective in patients with mild to moderate elevations of LDL-C.1,2 When administered as monotherapy these agents have the potential to reduce LDL-C by 10 to 24%.2 Bile acid sequestrants are also effective as add on therapy in patients with markedly elevated LDL-C who are already receiving a hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) or niacin.1,2 According to treatment guidelines, in patients who require LDL-C lowering and who do not achieve lipid goals with the use of a statin alone, consideration should be given to either increasing the dose of the statin or to adding a bile acid sequestrant or niacin to treatment.1 Bile acid sequestrants can also be added to statins for the treatment of heterozygous familial hypercholesterolemia, and they are recognized as the therapy of choice for the management of pruritus associated with primary biliary cirrhosis.3,4 There are three bile acid sequestrants available including cholestyramine (Prevalite®, Questran®, Questran Light®), colesevelam (Welchol®) and colestipol (Colestid®, Flavored Colestid®). All of the agents are Food and Drug Administration (FDA)-approved for adjunct treatment in patients with hypercholesterolemia.5-9 Cholestyramine is also FDA-approved for relief of pruritus associated with partial biliary obstruction.5,6 Colesevelam is also FDA-approved for use as monotherapy in children 10 to 17 years of age for the treatment of heterozygous familial hypercholesterolemia and as adjunct therapy to diet and exercise to improve glycemic control in adults with type 2 diabetes.9 Cholestyramine and colestipol are both available as powders (colestipol is available in two flavors) to be mixed with water or juice, and are typically administered once or twice daily with meals.5-8 Colestipol is also available as a tablet (Colestid®).7,8 Colesevelam is also available as a powder and as a tablet, and is typically administered once or twice daily.9 Colesevelam is more potent compared to either cholestyramine or colestipol.1 In addition, colesevelam may be more easily administered and better tolerated compared to the other agents.1,2 All bile acid sequestrants are available generically, with the exception of colesevelam (Welchol®). Table 1. Current Medications Available in the Therapeutic Class5-9 Generic Food and Drug Administration-Approved Dosage Form/ Generic (Trade Name) Indications Strength Availability Cholestyramine Adjunctive therapy to diet for the reduction of Powder: (Prevalite®*, elevated serum cholesterol in patients with 4 g ® Questran *, primary hypercholesterolemia who do not respond Questran adequately to diet†, relief of pruritus associated Light®*) with partial biliary obstruction‡ Colesevelam Adjunct to diet and exercise to improve glycemic Powder: (Welchol®) control in adults with type 2 diabetes, adjunct to 3.75 g diet and exercise to reduce elevated low density lipoprotein cholesterol levels in adults with primary Tablet: hyperlipidemia as monotherapy or in combination 625 mg - with a statin, monotherapy or in combination with a statin to reduce low density lipoprotein cholesterol levels in boys and postmenarchal girls 10 to 17 years of age with heterozygous familial hypercholesterolemia§ Colestipol Adjunctive therapy to diet for the reduction of Granules: (Colestid®*, elevated serum cholesterol and low density 5 g Flavored lipoprotein cholesterol in patients with primary Colestid®*) hypercholesterolemia who do not respond Powder: Page 1 of 4 Copyright 2013 • Review Completed on 07/22/2013 Therapeutic Class Overview: bile acid sequestrants Generic Food and Drug Administration-Approved Dosage Form/ Generic (Trade Name) Indications Strength Availability adequately to diet* 5 g Tablet: 1 g *Generic available in at least one dosage form and/or strength. †May be useful to lower low density lipoprotein cholesterol (LDL-C) levels in patients who also have hypertriglyceridemia, but it is not indicated where hypertriglyceridemia is the abnormality of most concern. ‡Has been shown to have a variable effect on serum cholesterol in these patients. Patients with primary biliary cirrhosis may exhibit elevated cholesterol as part of their disease. §If after an adequate trial of diet therapy the following findings are present: LDL-C remains ≥190 mg/dL or LDL-C remains ≥160 mg/dL and there is a positive family history of premature cardiovascular disease or two or more other cardiovascular disease risk factors are present in the pediatric patient. Evidence-based Medicine • Clinical trials have consistently demonstrated the “superiority” of bile acid sequestrants over placebo in the management of hyperlidpidemia.10-19 In line with current clinical guidelines, results demonstrated that the addition of a bile acid sequestrant to another lipid lowering agent has the potential to produce further reductions in low density lipoprotein cholesterol levels compared to monotherapy with either of the agents.17-21 • The Lipid Research Clinical Coronary Primary Prevention trial demonstrated that compared to placebo, treatment with cholestyramine reduced the risk of coronary heart disease death and/or nonfatal myocardial infarction in asymptomatic males with primary hypercholesterolemia (P<0.05).22,23 • Several placebo-controlled trials have demonstrated the safety and efficacy of colesevelam as adjunct therapy in adults with type 2 diabetes. Significant reductions in glycosylated hemoglobin (HbA1c) levels were observed when colesevelam was added to stable oral antidiabetic treatment regimens. A small (N=169), 16-week trial demonstrated that least squares mean reductions in HbA1c levels with colesevelam were comparable to either thiazolidinediones or dipeptidyl peptidase 4 inhibitors when added to background metformin therapy.24-31 • In a Cochrane Review of six randomized controlled trials, the addition of colesevelam to other hypoglycemic agents significantly reduced HbA1c compared to placebo (mean difference, -0.5%; P<0.00001). In addition, colesevelam with add-on hypoglycemic agents demonstrated a significant reduction in fasting plasma glucose compared to placebo (mean difference, -15 mg/dL; P<0.0001).32 Key Points within the Medication Class • According to Current Clinical Guidelines: o Therapeutic lifestyle changes remain an essential modality in the management of patients with hypercholesterolemia.1,3,33 o In general, hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) are considered first-line therapy for decreasing low density lipoprotein cholesterol (LDL-C) levels. If after six weeks, lipid goals are not achieved with statin monotherapy, a dosage increase or the addition of a bile acid sequestrant or niacin should be considered.1 o Statins are also considered first-line in the treatment of heterozygous familial hypercholesterolemia, but if required a bile acid sequestrant can be added to therapy.3 o Bile acid sequestrants are recognized as the therapy of choice for the management of pruritus associated with primary biliary cirrhosis.4 o In the management of patients with diabetes, the American Association of Clinical Endocrinologists note that colesevelam may provide a possible benefit or few adverse events when given as part of dual or triple therapy in addition to metformin in patients with a glycosylated hemoglobin of ≥7.5%.34 o In general, the American Diabetes Association recommends that a statin be added to lifestyle therapy, regardless of baseline lipid levels, in patients with diabetes. If maximally tolerated doses of statins fail to significantly lower LDL-C (<30% reduction from baseline), no strong evidence exists that combination therapy should be used. Niacin, fenofibrate, ezetimibe, and bile acid sequestrants offer additional LDL-C lowering compared to statins alone; however, Page 2 of 4 Copyright 2013 • Review Completed on 07/22/2013 Therapeutic Class Overview: bile acid sequestrants there is no evidence that combination therapy provides a significant cardiovascular disease risk reduction over statin therapy alone.35 • Other Key Facts: o All of the bile acid sequestrants are available as a powder, while colesevelam and colestipol are also available as a tablet. o All bile acid sequestrants are administered once or twice daily. o Cholestyramine and colesevelam have additional Food and Drug Administration-approved indications other than management of hypercholesterolemia. o Colesevelam is the most potent bile acid sequestrant and may be more easily administered and better tolerated compared to the other agents.1,2 o Cholestyramine and colestipol are available generically. References 1. National Cholesterol Education Program (NCEP). Detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III) final report, 2002 [guideline on the internet]. NCEP. 2002 [cited 2013 Jul 22]. Available from: http://www.nhlbi.nih.gov/guidelines/cholesterol/index.htm. 2. Rosenson RS. Lipid lowering with drugs other than statins and fibrates. In: Basow DS (Ed). UpToDate [database on the internet]. Waltham (MA): UpToDate; 2013 [cited
Load more

Recommended publications
  • Effects of Pitavastatin, Atorvastatin, and Rosuvastatin on the Risk Of
    biomedicines Article Effects of Pitavastatin, Atorvastatin, and Rosuvastatin on the Risk of New-Onset Diabetes Mellitus: A Single-Center Cohort Study Wei-Ting Liu 1, Chin Lin 2,3,4, Min-Chien Tsai 5, Cheng-Chung Cheng 6, Sy-Jou Chen 7,8, Jun-Ting Liou 6 , Wei-Shiang Lin 6, Shu-Meng Cheng 6, Chin-Sheng Lin 6,* and Tien-Ping Tsao 6,9,* 1 Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan; [email protected] 2 School of Public Health, National Defense Medical Center, Taipei 11490, Taiwan; [email protected] 3 School of Medicine, National Defense Medical Center, Taipei 11490, Taiwan 4 Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan, 5 Department of Physiology and Biophysics, Graduate Institute of Physiology, National Defense Medical Center, Taipei 11490, Taiwan; [email protected] 6 Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan; [email protected] (C.-C.C.); [email protected] (J.-T.L.); [email protected] (W.-S.L.); [email protected] (S.-M.C.) 7 Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan; [email protected] 8 Graduate Institute of Injury Prevention and Control, College of Public Health and Nutrition, Taipei Medical University, Taipei 11031, Taiwan 9 Division of Cardiology, Cheng Hsin General Hospital, Taipei 11220, Taiwan * Correspondence: [email protected] (C.-S.L.); [email protected] (T.-P.T.); Tel.: +886-2-6601-2656 (C.-S.L.); +886-2-2826-4400 (T.-P.T.) Received: 25 October 2020; Accepted: 11 November 2020; Published: 13 November 2020 Abstract: Statins constitute the mainstay treatment for atherosclerotic cardiovascular disease, which is associated with the risk of new-onset diabetes mellitus (NODM).
    [Show full text]
  • 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
    [Show full text]
  • Nustendi, INN-Bempedoic Acid, Ezetimibe
    Summary of risk management plan for Nustendi (Bempedoic acid/Ezetimibe) This is a summary of the risk management plan (RMP) for Nustendi. The RMP details important risks of Nustendi, how these risks can be minimized, and how more information will be obtained about Nustendi's risks and uncertainties (missing information). Nustendi's summary of product characteristics (SmPC) and its package leaflet give essential information to healthcare professionals and patients on how Nustendi should be used. This summary of the RMP for Nustendi should be read in the context of all this information, including the assessment report of the evaluation and its plain-language summary, all which is part of the European Public Assessment Report (EPAR). Important new concerns or changes to the current ones will be included in updates of Nustendi's RMP. I. The Medicine and What It Is Used For Nustendi is authorized for treatment of primary hypercholesterolemia in adults, as an adjunct to diet (see SmPC for the full indication). It contains bempedoic acid as the active substance and it is given by mouth. Further information about the evaluation of Nustendi’s benefits can be found in Nustendi’s EPAR, including in its plain-language summary, available on the EMA website, under the medicine’s webpage https://www.ema.europa.eu/en/medicines/human/EPAR/nustendi II. Risks Associated With the Medicine and Activities to Minimize or Further Characterize the Risks Important risks of Nustendi, together with measures to minimize such risks and the proposed studies for learning
    [Show full text]
  • Lipid Lowering Agents, Cognitive Decline, and Dementia: the Three-City Study
    Lipid lowering agents, cognitive decline, and dementia: the three-city study. Marie-Laure Ancelin, Isabelle Carrière, Pascale Barberger-Gateau, Sophie Auriacombe, Olivier Rouaud, Spiros Fourlanos, Claudine Berr, Anne-Marie Dupuy, Karen Ritchie To cite this version: Marie-Laure Ancelin, Isabelle Carrière, Pascale Barberger-Gateau, Sophie Auriacombe, Olivier Rouaud, et al.. Lipid lowering agents, cognitive decline, and dementia: the three-city study.: Lipid Lowering Agents and Cognitive Decline. Journal of Alzheimer’s Disease, IOS Press, 2012, 30 (3), pp.629-37. 10.3233/JAD-2012-120064. inserm-00707350 HAL Id: inserm-00707350 https://www.hal.inserm.fr/inserm-00707350 Submitted on 12 Jun 2012 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Lipid lowering agents, cognitive decline, and dementia: the three-city study Marie-Laure Ancelin 1 * , Isabelle Carrière 1 , Pascale Barberger-Gateau 2 , Sophie Auriacombe 2 , Olivier Rouaud 3 , Spiros Fourlanos 4 , Claudine Berr 1 , Anne-Marie Dupuy 1 5 , Karen Ritchie 1 6 1 Neuropsychiatrie : Recherche Epidémiologique
    [Show full text]
  • Pharmacy Prior Authorization Non-Formulary and Prior
    Pharmacy Prior Authorization Non-Formulary and Prior Authorization Guidelines Scroll down to see PA Criteria by drug class, or Ctrl+F to search document by drug name PA Guideline Requirements Duration of Approval if Requirements Are Met Non-Formulary Requests for Non-Formulary Medications that do not have specific Prior Authorization Initial Approval: Medication Guidelines will be reviewed based on the following: • Minimum of 3 months, Guideline • An appropriate diagnosis/indication for the requested medication, depending on the • An appropriate dose of medication based on age and indication, diagnosis, to determine • Documented trial of 2 formulary agents for an adequate duration have not been effective or adherence, efficacy and tolerated patient safety monitoring OR • All other formulary medications are contraindicated based on the patient’s diagnosis, other Renewal: medical conditions or other medication therapy, • Minimum of 6 months OR • Maintenance medications • There are no other medications available on the formulary to treat the patient’s condition may be approved Indefinite Maryland Physicians Care determines patient medication trials and adherence by a review of pharmacy claims data over the preceding twelve months. Additional information may be requested on a case-by-case basis to allow for proper review. Medications Requests for Medications requiring Prior Authorization (PA) will be reviewed based on the PA As documented in the requiring Prior Guidelines/Criteria for that medication. Scroll down to view the PA Guidelines for specific individual guideline Authorization medications. Medications that do not have a specific PA guideline will follow the Non-Formulary Medication Guideline. Additional information may be required on a case-by-case basis to allow for adequate review.
    [Show full text]
  • Atorvastatin Slows the Progression of Cardiac Remodeling in Mice with Pressure Overload and Inhibits Epidermal Growth Factor Receptor Activation
    335 Hypertens Res Vol.31 (2008) No.2 p.335-344 Original Article Atorvastatin Slows the Progression of Cardiac Remodeling in Mice with Pressure Overload and Inhibits Epidermal Growth Factor Receptor Activation Yulin LIAO1), Hui ZHAO2), Akiko OGAI1), Hisakazu KATO2), Masanori ASAKURA1), Jiyoong KIM1), Hiroshi ASANUMA1), Tetsuo MINAMINO2), Seiji TAKASHIMA2), and Masafumi KITAKAZE1) The aim of this study was to investigate whether atorvastatin inhibits epidermal growth factor receptor (EGFR) activation in cardiomyocytes in vitro and slows the progression of cardiac remodeling induced by pressure overload in mice. Either atorvastatin (5 mg/kg/day) or vehicle was orally administered to male C57BL/6J mice with transverse aortic constriction (TAC). Physiological parameters were obtained by echocardiography or left ventricular (LV) catheterization, and morphological and molecular parameters of the heart were also examined. Furthermore, cultured neonatal rat cardiomyocytes were studied to clarify the underlying mechanisms. Four weeks after TAC, atorvastatin reduced the heart/body weight and lung/body weight ratios (8.69±0.38 to 6.45±0.31 mg/g (p<0.001) and 10.89±0.68 to 6.61±0.39 mg/g (p<0.01) in TAC mice with and without atorvastatin, respectively). Decrease of LV end-diastolic pressure and the time con- stant of relaxation, increased fractional shortening, downregulation of a disintegrin and metalloproteinase (ADAM)12, ADAM17 and heparin-binding epidermal growth factor genes, and reduction of the activity of EGFR and extracellular signal–regulated kinase (ERK) were observed in the atorvastatin group. Phenyleph- rine-induced protein synthesis, phosphorylation of EGFR, and activation of ERK in neonatal rat cardiomyo- cytes were all inhibited by atorvastatin.
    [Show full text]
  • Role of Colesevelam in Combination Lipid-Lowering Therapy
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Springer - Publisher Connector Am J Cardiovasc Drugs (2013) 13:315–323 DOI 10.1007/s40256-013-0037-0 REVIEW ARTICLE Role of Colesevelam in Combination Lipid-Lowering Therapy Michael R. Jones • Oliseyenum M. Nwose Published online: 3 August 2013 Ó The Author(s) 2013. This article is published with open access at Springerlink.com Abstract Hyperlipidemia is associated with an increased ezetimibe, statin plus niacin, or statin plus ezetimibe) and risk of cardiovascular events; reducing low-density lipo- high-sensitivity C-reactive protein (with statins), and protein cholesterol (LDL-C), the primary target for cho- increases in apo A-I (with statins, ezetimibe, or statins plus lesterol-lowering therapy, lowers the risk for such events. niacin). Triglyceride levels remained relatively unchanged Although bile acid sequestrants were the first class of drugs when colesevelam was combined with statins, fibrates, to show a mortality benefit related to LDL-C lowering, ezetimibe, or statin plus ezetimibe, and decreased with the statins are now considered first-line pharmacological ther- triple combination of colesevelam, statin, and niacin. apy for reducing LDL-C levels because of their potency Colesevelam offset the negative glycemic effects of statins and their remarkable record of successful outcomes studies. and niacin in subjects with insulin resistance or impaired Nevertheless, a substantial proportion of patients do not glucose tolerance. Colesevelam was generally well toler- achieve LDL-C goals with statin monotherapy. In addition, ated when added to other lipid-lowering therapies in clin- because of adverse effects (primarily myopathy), some ical trials, with gastrointestinal effects such as constipation patients may be unwilling to use or unable to tolerate statin being the predominant adverse events.
    [Show full text]
  • Cholestagel®) Combination and Monotherapy for Familial Hypercholesterolaemia
    New Medicine Recommendation Colesevelam (Cholestagel®) Combination and monotherapy for familial hypercholesterolaemia Recommendation: Black - NOT recommended for use by the NHS in Lancashire. Colesevelam (Cholestagel®) is NOT recommended as combination or monotherapy for familial hypercholesterolaemia. Clinical evidence indicates that the drug is poorly tolerated and the trials were weak in significant areas such as the inclusion of small numbers of patients, only demonstrating surrogate endpoints or being conducted using nonstandard co-administered drugs. There are similar, established drugs for the treatment of the condition for which there were no head to head trials with Colesevalam therefore relative clinical efficacy cannot be directly demonstrated. Summary of supporting evidence: Primary dyslipidaemias, including familial hypercholesterolaemia (FH), are lipid disorders that are genetic in origin. FH is the most common inherited lipid metabolism disorder in its heterozygous form. In the UK heterozygous FH affects 1 in 500 of the UK population. [1] Statin therapy is the first-line treatment for patients with the vast majority of dyslipidaemias. NICE CG 71 recommends the prescribing of a high-intensity statin at the maximum licensed dose or at the maximum tolerated dose to achieve a reduction in LDL cholesterol concentration of greater than 50% from baseline. [2] Colesevelam is a lipid-lowering polymer that binds bile acids in the intestine, impeding their reabsorption. [3] Colesevelam is a third-line agent, behind statins and ezetimibe. [2] The main body of evidence for the use of colesevelam in familial hypercholesterolaemia comes from the European Public Assessment Reports (EPAR). Study GTC-48-301 was a randomised, double-blind, parallel design, placebo-controlled pivotal phase III dose-response study.
    [Show full text]
  • FIELD Study Revealed Fenofibrate Reduced Need for Laser Treatment for Diabetic Retinopathy by Anthony C
    Supplement to Supported by an unrestricted educational grant from Abbott Laboratories March/April 2008 FIELD Study Revealed Fenofibrate Reduced Need for Laser Treatment for Diabetic Retinopathy By Anthony C. Keech, MBBS, Msc Epid, FRANZCS, FRACP; and Paul Mitchell, MBBS(Hons), MD, PhD, FRANZCO, FRACS, FRCOphth, FAFPHM This agent’s mechanism of benefit in diabetic retinopathy appears to go beyond its effects on lipid concentration or blood pressure, and this potential mechanism of action operates even when glycemic control and blood pressure levels are within goal. ABSTRACT icant relative reduction was seen of almost one-third in PURPOSE the rate of first laser application for retinopathy after The FIELD (Fenofibrate Intervention and Event an average treatment duration of 5 years with fenofi- Lowering in Diabetes) study sought to investigate brate 200 mg/day. whether long-term lipid-lowering therapy with fenofi- In this report, we detail the effects of fenofibrate brate would reduce macro- and microvascular compli- administration on ophthalmic microvascular compli- cations among patients with type 2 diabetes. We previ- cations and attempt to clarify some of the underlying ously reported that in type 2 diabetes patients with pathologies being addressed among patients undergo- adequate glycemic and blood pressure control, a signif- ing laser treatment. Jointly sponsored by The Dulaney Foundation and Retina Today MARCH/APRIL 2008 I SUPPLEMENT TO RETINA TODAY I 1 FIELD Study Revealed Fenofibrate Reduced Need for Laser Treatment for Diabetic Retinopathy Jointly sponsored by The Dulaney Foundation and Retina Today. Release date: April 2008. Expiration date: April 2009. This continuing medical education activity is supported by an unrestricted educational grant from Abbott Laboratories.
    [Show full text]
  • Pharmacological Agents Currently in Clinical Trials for Disorders in Neurogastroenterology
    Pharmacological agents currently in clinical trials for disorders in neurogastroenterology Michael Camilleri J Clin Invest. 2013;123(10):4111-4120. https://doi.org/10.1172/JCI70837. Clinical Review Esophageal, gastrointestinal, and colonic diseases resulting from disorders of the motor and sensory functions represent almost half the patients presenting to gastroenterologists. There have been significant advances in understanding the mechanisms of these disorders, through basic and translational research, and in targeting the receptors or mediators involved, through clinical trials involving biomarkers and patient responses. These advances have led to relief of patients’ symptoms and improved quality of life, although there are still significant unmet needs. This article reviews the pipeline of medications in development for esophageal sensorimotor disorders, gastroparesis, chronic diarrhea, chronic constipation (including opioid-induced constipation), and visceral pain. Find the latest version: https://jci.me/70837/pdf Review Pharmacological agents currently in clinical trials for disorders in neurogastroenterology Michael Camilleri Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, Minnesota, USA. Esophageal, gastrointestinal, and colonic diseases resulting from disorders of the motor and sensory functions represent almost half the patients presenting to gastroenterologists. There have been significant advances in under- standing the mechanisms of these disorders, through basic and translational research, and in targeting the recep- tors or mediators involved, through clinical trials involving biomarkers and patient responses. These advances have led to relief of patients’ symptoms and improved quality of life, although there are still significant unmet needs. This article reviews the pipeline of medications in development for esophageal sensorimotor disorders, gastropa- resis, chronic diarrhea, chronic constipation (including opioid-induced constipation), and visceral pain.
    [Show full text]
  • 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.
    [Show full text]
  • Bempedoic Acid) Tablets, for Oral Use Most Common (Incidence ≥ 2% and Greater Than Placebo) Adverse Reactions Initial U.S
    HIGHLIGHTS OF PRESCRIBING INFORMATION • Tendon Rupture: Tendon rupture has occurred. Discontinue NEXLETOL These highlights do not include all the information needed to use at the first sign of tendon rupture. Avoid NEXLETOL in patients who NEXLETOL™ safely and effectively. See full prescribing information have a history of tendon disorders or tendon rupture. (5.2) for NEXLETOL. --------------------------------ADVERSE REACTIONS----------------------------­ NEXLETOL (bempedoic acid) tablets, for oral use Most common (incidence ≥ 2% and greater than placebo) adverse reactions Initial U.S. Approval: 2020 are upper respiratory tract infection, muscle spasms, hyperuricemia, back pain, abdominal pain or discomfort, bronchitis, pain in extremity, anemia, ----------------------------INDICATIONS AND USAGE--------------------------­ and elevated liver enzymes. (6.1) NEXLETOL is an adenosine triphosphate-citrate lyase (ACL) inhibitor indicated as an adjunct to diet and maximally tolerated statin therapy for the To report SUSPECTED ADVERSE REACTIONS, contact Esperion at treatment of adults with heterozygous familial hypercholesterolemia or 833-377-7633 (833 ESPRMED) or FDA at 1-800-FDA-1088 or established atherosclerotic cardiovascular disease who require additional www.fda.gov/medwatch. lowering of LDL-C. (1) --------------------------------DRUG INTERACTIONS----------------------------­ Limitations of Use: The effect of NEXLETOL on cardiovascular morbidity • Simvastatin: Avoid concomitant use of NEXLETOL with simvastatin and mortality has not been
    [Show full text]