I NDA/BLA Multi-Disciplinary Review and Evaluation

Total Page:16

File Type:pdf, Size:1020Kb

I NDA/BLA Multi-Disciplinary Review and Evaluation NDA 021200 S015 Zelnorm (tegaserod) NDA/BLA Multi-Disciplinary Review and Evaluation Application Type sNDA Application Number(s) 021200, s015 Priority or Standard Standard Submit Date(s) 2/26/2018 Received Date(s) 2/26/2018 PDUFA Goal Date 12/26/2018 Division/Office DGIEP/ODE III Review Completion Date 3/22/2019 Established/Proper Name Tegaserod Maleate (Proposed) Trade Name Zelnorm Pharmacologic Class Serotonin (5-HT4) receptor agonist Applicant Sloan Pharma S.a.r.l, Bertrange, Cham Branch Authorized US Agent: US WorldMed, LLC Dosage form Oral tablets Applicant proposed Dosing 6 mg twice daily Regimen Applicant Proposed Treatment of women less than 65 years with irritable bowel Indication(s)/Population(s) syndrome with constipation (IBS-C). (Proposed contraindications: history of myocardial infarction, stroke, transient ischemic attack, or angina, and more than one cardiovascular risk factor: hypertension, tobacco use, diabetes, hypercholesterolemia, age ≥55 years, and obesity). Recommendation on Approval Regulatory Action Recommended Treatment of adult women less than 65 years of age with irritable Indication(s)/Population(s) bowel syndrome with constipation (if applicable) (Contraindication: history of myocardial infarction, stroke, transient ischemic attack, or angina). Recommended Dosing 6 mg twice daily Regimen i Reference ID: 4407897 NDA 021200 S015 Zelnorm (tegaserod) Table of Contents Reviewers of Multi-Disciplinary Review and Evaluation .............................................. 1 Glossary ......................................................................................................................... 3 1. Executive Summary ................................................................................................... 5 1.1. Product Introduction .......................................................................................... 6 1.2. Conclusions on the Substantial Evidence of Effectiveness ................................ 7 1.3. Benefit-Risk Assessment .................................................................................... 9 1.4. Patient Experience Data ................................................................................... 19 2. Therapeutic Context ............................................................................................... 20 2.1. Analysis of Condition ........................................................................................ 20 2.2. Analysis of Current Treatment Options ........................................................... 21 3. Relevant Regulatory History ................................................................................... 23 3.1. U.S. Regulatory Actions and Marketing History ............................................... 23 3.2. Summary of Presubmission/Submission Regulatory Activity .......................... 23 4. Significant Issues from Other Review Disciplines Pertinent to Clinical Conclusions on Efficacy and Safety ....................................................................... 27 4.1. Office of Scientific Investigations ..................................................................... 27 4.2. Product Quality................................................................................................. 27 4.3. Clinical Microbiology ........................................................................................ 28 4.4. Devices and Companion Diagnostic Issues ...................................................... 29 5. Statistical and Clinical Evaluation of Efficacy .......................................................... 29 5.1. Review Strategy for Efficacy and Overview of the Clinical Development Program for IBS-C .............................................................................................. 29 5.2. Phase 3 Trial Design .......................................................................................... 30 5.2.1. Primary Endpoint ....................................................................................... 31 5.2.2. Severely Symptomatic IBS-C Subpopulation ............................................. 35 5.3. Efficacy Conclusions ......................................................................................... 36 6. Evaluation of Overall Safety .................................................................................... 37 6.1. Safety Review Approach................................................................................... 37 6.2. Review of the Safety Database ........................................................................ 39 6.2.1. Exposure .................................................................................................... 39 6.2.2. Adequacy of the Safety Database .............................................................. 40 6.3. Safety Results ................................................................................................... 41 6.3.1. Deaths ........................................................................................................ 41 6.3.2. Serious Adverse Events .............................................................................. 41 ii Reference ID: 4407897 NDA 021200 S015 Zelnorm (tegaserod) 6.3.3. Dropouts and/or Discontinuations Due to Adverse Effects ...................... 42 6.3.4. Treatment Emergent Adverse Events and Adverse Reactions .................. 42 6.4. Safety Analyses by Demographic Subgroups ................................................... 43 6.5. Analysis of Submission-Specific Safety Issues .................................................. 43 6.6. Safety Concerns Identified Through Postmarket Experience .......................... 44 7. Cardiovascular Events of Special Interest ............................................................... 47 7.1. Nonclinical Pharmacology/Toxicology ............................................................. 47 7.1.1. Executive Summary ................................................................................... 47 7.1.2. Referenced NDAs, BLAs, DMFs .................................................................. 48 7.1.3. Serotonin Receptor Selectivity Studies...................................................... 48 7.1.4. In Vitro Cardiac Electrophysiology Studies ................................................ 49 7.1.5. Effects on Contractility of Coronary Arteries ............................................ 50 7.1.6. In Vivo Nonclinical Cardiovascular Safety Pharmacology Studies ............. 50 7.2. Clinical Pharmacology ...................................................................................... 50 7.2.1. Executive Summary ................................................................................... 50 7.2.2. Clinical Pharmacokinetics .......................................................................... 51 7.2.3. Specific Populations ................................................................................... 51 7.2.4. Drug-Drug Interactions Studies ................................................................. 52 7.2.5. Effects on Platelet Aggregation ................................................................. 54 7.3. Clinical and Statistical Evaluation ..................................................................... 57 7.3.1. Characterization of the CV Safety Signal, Including MACE ........................ 57 7.3.2. Statistical Perspective ................................................................................ 65 7.3.3. Adjudications ............................................................................................. 67 7.3.4. Other Elements of CV Safety Signal, Including Arrhythmia, Long-Term Safety, ECG (and QT Prolongation), and Blood Pressure............................... 73 7.3.4.1. Arrhythmic Events ............................................................................... 73 7.3.4.2. Long-Term (Open-label) Use ............................................................... 75 7.3.4.3. ECG Findings (Including QT) ................................................................ 76 7.3.4.4. Vital Signs Data (Including Blood Pressure) ........................................ 78 7.3.5. Patient Demographic and Baseline CV Risk Characteristics ...................... 79 7.3.6. CVI Signal by Subpopulations – Assessment of Proposed Reintroduction Populations ........................................................................... 84 7.3.7. CV Signal from Clinical Trials: Conclusions ................................................ 87 7.4. Postmarketing/Epidemiologic Study ................................................................ 88 7.4.1. Division of Epidemiology Review of Observational Study ......................... 88 iii Reference ID: 4407897 NDA 021200 S015 Zelnorm (tegaserod) 8. Neuropsychiatric Adverse Events of Interest ......................................................... 91 8.1. Clinical .............................................................................................................. 91 8.2. Postmarketing/Epidemiology ........................................................................... 95 8.2.1. Division of Pharmacovigilance Analysis of Postmarketing Suicidal Ideation and Behavior Events ............................ Error! Bookmark not defined. 8.2.2. Division of Epidemiology Review of Observational Study ......................... 95 9. Summary of Safety .................................................................................................. 96 10. Advisory
Recommended publications
  • Laxatives for the Management of Constipation in People Receiving Palliative Care (Review)
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by UCL Discovery Laxatives for the management of constipation in people receiving palliative care (Review) Candy B, Jones L, Larkin PJ, Vickerstaff V, Tookman A, Stone P This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2015, Issue 5 http://www.thecochranelibrary.com Laxatives for the management of constipation in people receiving palliative care (Review) Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. TABLE OF CONTENTS HEADER....................................... 1 ABSTRACT ...................................... 1 PLAINLANGUAGESUMMARY . 2 BACKGROUND .................................... 2 OBJECTIVES ..................................... 4 METHODS ...................................... 4 RESULTS....................................... 7 Figure1. ..................................... 8 Figure2. ..................................... 9 Figure3. ..................................... 10 DISCUSSION ..................................... 13 AUTHORS’CONCLUSIONS . 14 ACKNOWLEDGEMENTS . 14 REFERENCES ..................................... 15 CHARACTERISTICSOFSTUDIES . 17 DATAANDANALYSES. 26 ADDITIONALTABLES. 26 APPENDICES ..................................... 28 WHAT’SNEW..................................... 35 HISTORY....................................... 35 CONTRIBUTIONSOFAUTHORS . 36 DECLARATIONSOFINTEREST . 36 SOURCESOFSUPPORT . 36 DIFFERENCES
    [Show full text]
  • THE HARD TRUTH ABOUT PROKINETIC MEDICATION USE in PETS Introduction Pathophysiology/Etiology to That Observed in Dogs
    VETTALK Volume 15, Number 04 American College of Veterinary Pharmacists THE HARD TRUTH ABOUT PROKINETIC MEDICATION USE IN PETS Introduction Pathophysiology/Etiology to that observed in dogs. It can be The moving topic of this Vet Talk As with most diseases in the veteri- due to a trichobezoar, dehydration, newsletter will be prokinetic medica- nary world, the etiology and patho- obesity, old age, diabetes, immobility, tions. The availability of information physiology of constipation are varied pain from trauma to the low back, on the many prokinetic agents is var- depending on the species being dis- bladder infection, or an anal sac infec- ied at best so an overall consensus of cussed, where in their gastrointestinal tion. In cases that are more chronic, prokinetic medications will be as- tract the problem is occurring, and underlying disease such as colitis or sessed in this article, hopefully giving any accompanying comorbid condi- Irritable Bowel Syndrome (IBS) may better insight to practitioners about tions. be the culprit. On the other hand, the which agents to use in their patients. cause may be idiopathic which is Canines: In man’s best friend, consti- frustrating for both veterinarian and Prevalence pation has many origins. A dog’s patient since this form is most diffi- Chronic constipation and gastroin- digestive tract itself is complex but cult to treat. testinal stasis are highly debilitating ultimately the mass movements and conditions that not only affect human haustral contractions from the large Equines: Despite their large size, patients but our four legged patients intestine (colon), propel feces into the horses have incredibly delicate diges- as well! Though this condition is rectum stimulating the internal anal tive systems.
    [Show full text]
  • The Pharmacology of Prokinetic Agents and Their Role in the Treatment of Gastrointestinal Disorders
    The Pharmacology of ProkineticAgents IJGE Issue 4 Vol 1 2003 Review Article The Pharmacology of Prokinetic Agents and Their Role in the Treatment of Gastrointestinal Disorders George Y. Wu, M.D, Ph.D. INTRODUCTION Metoclopramide Normal peristalsis of the gut requires complex, coordinated neural and motor activity. Pharmacologic Category : Gastrointestinal Abnormalities can occur at a number of different Agent. Prokinetic levels, and can be caused by numerous etiologies. This review summarizes current as well as new Symptomatic treatment of diabetic gastric agents that show promise in the treatment of stasis gastrointestinal motility disorders. For these Gastroesophageal reflux e conditions, the most common medications used in s Facilitation of intubation of the small the US are erythromycin, metoclopramide, and U intestine neostigmine (in acute intestinal pseudo- Prevention and/or treatment of nausea and obstruction). A new prokinetic agent, tegaserod, vomiting associated with chemotherapy, has been recently approved, while other serotonin radiation therapy, or post-surgery (1) agonist agents (prucalopride, YM-31636, SK-951, n ML 10302) are currently undergoing clinical o Blocks dopamine receptors in chemoreceptor i t studies. Other prokinetics, such as domperidone, c trigger zone of the CNS (2) A are not yet approved in the US, although are used in f Enhances the response to acetylcholine of o other countries. tissue in the upper GI tract, causing enhanced m s i n motility and accelerated gastric emptying a DELAYED GASTRIC EMPTYING OR h without stimulating gastric, biliary, or c G A S T R O E S O P H A G E A L R E F L U X e pancreatic secretions.
    [Show full text]
  • 3.2.2 Misuse of Stimulant Laxatives
    Medicines Adverse Reactions Committee Meeting date 10/06/2021 Agenda item 3.2.2 Title Misuse of stimulant laxatives Submitted by Medsafe Pharmacovigilance Paper type For advice Team Active ingredient Product name Sponsor Bisacodyl Bisacodyl Laxative (Pharmacy Health) PSM Healthcare Limited trading as API tablet Consumer Brands Dulcolax tablet Sanofi-Aventis New Zealand Limited Dulcolax Suppository Sanofi-Aventis New Zealand Limited *Lax-Suppositories Bisacodyl AFT Pharmaceuticals Limited *Lax-Tab tablet AFT Pharmaceuticals Limited Docusate sodium *Coloxyl tablet Pharmacy Retailing (New Zealand) Limited trading as Healthcare Logistics Docusate sodium + Coloxyl with Senna tablet Pharmacy Retailing (New Zealand) sennosides Limited trading as Healthcare Logistics *Laxsol tablet Pharmacy Retailing (New Zealand) Limited trading as Healthcare Logistics Glycerol *Glycerol Suppositories PSM Healthcare Limited trading as API Consumer Brands Sennosides *Senokot tablet Reckitt Benckiser (New Zealand) Limited Sodium picosulfate Dulcolax SP Drops oral solution Sanofi-Aventis New Zealand Limited PHARMAC funding *Pharmaceutical Schedule Lax-Tab tablets, Lax-Suppositories Bisacodyl, Coloxyl tablets and Glycerol Suppositories are fully-funded only on a prescription. Senokot tablets are part- funded. Previous MARC Misuse of stimulant laxatives has not been discussed previously. meetings International action Following a national safety review published in August 2020, the MHRA in the UK has introduced pack size restrictions, revised recommended ages for use
    [Show full text]
  • 1: Gastro-Intestinal System
    1 1: GASTRO-INTESTINAL SYSTEM Antacids .......................................................... 1 Stimulant laxatives ...................................46 Compound alginate products .................. 3 Docuate sodium .......................................49 Simeticone ................................................... 4 Lactulose ....................................................50 Antimuscarinics .......................................... 5 Macrogols (polyethylene glycols) ..........51 Glycopyrronium .......................................13 Magnesium salts ........................................53 Hyoscine butylbromide ...........................16 Rectal products for constipation ..........55 Hyoscine hydrobromide .........................19 Products for haemorrhoids .................56 Propantheline ............................................21 Pancreatin ...................................................58 Orphenadrine ...........................................23 Prokinetics ..................................................24 Quick Clinical Guides: H2-receptor antagonists .......................27 Death rattle (noisy rattling breathing) 12 Proton pump inhibitors ........................30 Opioid-induced constipation .................42 Loperamide ................................................35 Bowel management in paraplegia Laxatives ......................................................38 and tetraplegia .....................................44 Ispaghula (Psyllium husk) ........................45 ANTACIDS Indications:
    [Show full text]
  • Tegaserod in the Treatment of Constipation-Predominant Functional Gastrointestinal Disorders
    DRUG PROFILE Tegaserod in the treatment of constipation-predominant functional gastrointestinal disorders Anurag Agrawal & Irritable bowel syndrome is a common condition for which, until recently, treatment Peter Whorwell† options have been limited. Tegaserod has selective serotonin subtype 4 receptor agonist †Author for correspondence activity and acts by increasing gastrointestinal motility, secretion and possibly reducing ERC Building, First Floor, Wythenshawe Hospital, visceral sensitivity. It has been developed to treat patients with irritable bowel syndrome Southmoor Road, who suffer from abdominal pain, constipation and bloating. Studies so far suggest that it is Manchester, M23 9LT, an effective treatment for these symptoms with an excellent safety profile. Its role in other UK Tel.: +44 161 291 5813 functional gastrointestinal disorders, such as functional dyspepsia, is still being assessed. Fax: +44 161 291 4184 This review describes the structure, pharmacokinetic and pharmacodynamic properties of tegaserod and its effect on gastrointestinal physiology, as well as its clinical utility. Irritable bowel syndrome (IBS) is the most com- drugs such as antidiarrheals, laxatives, antispas- mon condition dealt with by gastroenterolo- modics and antidepressants. Behavioral therapy gists, accounting for up to 30% of their practice is sometimes tried in patients who do not and 10% of primary care case loads [1]. It is respond to conventional treatment. characterized by abdominal pain or discomfort In addition to its costs to the patient, IBS also often related to a change in bowel habit and fre- has a significant direct and indirect economic quently exacerbated by eating. Investigation burden. The direct cost in terms of healthcare reveals no structural abnormality, although a utilization has been estimated to be between variety of gastrointestinal (GI) physiological US$1.7–10 billion/year in the USA alone.
    [Show full text]
  • Zelnorm®) for Safety Reasons
    NATIONAL PBM BULLETIN April 3, 2007 DEPARTMENT OF VETERANS AFFAIRS VETERANS HEALTH ADMINISTRATION PHARMACY BENEFITS MANAGEMENT STRATEGIC HEALTHCARE GROUP, MEDICAL ADVISORY PANEL, AND CENTER FOR MEDICATION SAFETY (VA MEDSAFE) Discontinued Marketing of Tegaserod (Zelnorm®) for Safety Reasons I. ISSUE – On March 30, 2007, Novartis suspended US marketing and sales of tegaserod in compliance with the Food and Drug Administration’s (FDA) request which was based on a retrospective analysis of pooled clinical trial data showing increased risk of serious cardiovascular adverse events associated with use of tegaserod compared to placebo. II. BACKGROUND – Novartis reported results of an analysis involving 29 short-term randomized, controlled clinical trials of tegaserod which included over 18,000 patients in the clinical trial database. Serious cardiovascular events (angina, MI, and stroke) occurred in 13 of 11,614 (0.11%) tegaserod-treated patients compared to 1 of 7,031 (0.01%) placebo-treated patients (p=0.024). All patients affected had pre-existing cardiovascular disease. III. DISCUSSION – Tegaserod was approved in July 2002 for the short-term treatment of constipation-predominant irritable bowel syndrome (IBS) in women. Subsequently, the drug was approved in August 2004 for the treatment of chronic constipation in men and women under age 65. In January 2006, VA PBM provided criteria for nonformulary use of tegaserod based on available evidence reviewed in the PBM Drug Monograph for tegaserod. A preliminary utilization evaluation was conducted by VAMedSAFE to look at variations in prescribing patterns. Although not an approved indication, patients with gastroesophageal reflux disease (GERD) appeared to be the largest users of tegaserod.
    [Show full text]
  • Zelnorm Page: 1 of 5
    Federal Employee Program® 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.50.25 Section: Prescription Drugs Effective Date: April 1, 2020 Subsection: Gastrointestinal Agents Original Policy Date: April 26, 2019 Subject: Zelnorm Page: 1 of 5 Last Review Date: March 13, 2020 Zelnorm Description Zelnorm (tegaserod) Background Zelnorm is an agonist of serotonin type-4 (5-HT4) receptors that stimulates the peristaltic reflex and intestinal secretion, inhibits visceral sensitivity, enhances basal motor activity, and normalizes impaired motility throughout the gastrointestinal tract (1). Regulatory Status FDA-approved indication: Zelnorm is a serotonin-4 (5-HT4) receptor agonist indicated for treatment of adult women less than 65 years of age with irritable bowel syndrome with constipation (IBS-C) (1). Limitations of Use: The safety and effectiveness of Zelnorm in men with IBS-C have not been established (1). Zelnorm is contraindicated in patients with: (1) 1. A history of myocardial infarction (MI), stroke, transient ischemic attack (TIA), or angina. 2. A history of ischemic colitis or other forms of intestinal ischemia. 3. Severe renal impairment (eGFR < 15 mL/min/1.73 m2) or end-stage renal disease. 4. Moderate and severe hepatic impairment (Child-Pugh B or C). 5. A history of bowel obstruction, symptomatic gallbladder disease, suspected sphincter of Oddi Dysfunction, or abdominal adhesions. 5.50.25 Section: Prescription Drugs Effective Date: April 1, 2020 Subsection: Gastrointestinal Agents Original Policy Date: April 26, 2019 Subject: Zelnorm Page: 2 of 5 The safety and effectiveness of Zelnorm in pediatric patients less than 18 years of age have not been established (1).
    [Show full text]
  • Oral Lactulose Vs. Polyethylene Glycol for Bowel Preparation in Colonoscopy: a Randomized Controlled Study
    Open Access Original Article DOI: 10.7759/cureus.14363 Oral Lactulose vs. Polyethylene Glycol for Bowel Preparation in Colonoscopy: A Randomized Controlled Study Jagdeep Jagdeep 1 , Gaurish Sawant 1 , Pawan Lal 1 , Lovenish Bains 1 1. Department of Surgery, Maulana Azad Medical College, New Delhi, IND Corresponding author: Lovenish Bains, lovenishbains@gmail.com Abstract Background Colonoscopy is the method of choice to evaluate colonic mucosa and the distal ileum, allowing the diagnosis and treatment of many diseases. Appropriate bowel preparation necessitates the use of laxative medications, preferentially by oral administration. These include polyethylene glycol (PEG), sodium picosulfate, and sodium phosphate (NaP). Lactulose, a semi-synthetic derivative of lactose, undergoes fermentation, acidifying the gut environment, stimulates intestinal motility, and increases osmotic pressure within the lumen of the colon. Methods In this prospective randomized controlled study, we analyzed 40 patients who presented with symptomatic bleeding per rectum and underwent bowel preparation either with lactulose or polyethylene glycol for colonoscopy. The quality of bowel preparation and other variables like palatability, discomfort, and electrolyte levels were analyzed. Results The majority of the patients (90%) were comfortable with the taste of lactulose solution, whereas the PEG group patients (55%) were equally divided on its palatability. On lactulose consumption, 40% of patients reported nausea/vomiting and around 10% of patients complained of abdominal discomfort. Serum sodium levels showed insignificant changes from 4.33 ± 0.07 mEq/L to 4.21 ± 0.18 mEq/L while potassium also remained similar from 4.26 ± 0.03 mEq/L to 4.22 ± 0.17 mEq/L. The mean Boston Bowel Preparation Score (BBPS) in patients who received lactulose solution was 6.25 ± 0.786 and in those who received PEG solution, it was 6.35 ± 0.813 (P-value = 0.59).
    [Show full text]
  • Rifaximin (XIFAXAN)
    Rifaximin (XIFAXAN) for Irritable Bowel Syndrome with Diarrhea National Drug Monograph March 2016 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 Information Description/Mechanism of Minimally absorbed, broad-spectrum antibacterial that inhibits bacterial RNA Action synthesis. The specific mechanism of action of rifaximin in irritable bowel syndrome (IBS) has not been determined. The most likely mechanism of rifaximin is reduction in overall bacterial load, particularly in the large bowel1; however, rifaximin also seems to modulate gut microenvironment and produce cytoprotective effects.2 Indication(s) Under Review in Treatment of IBS with diarrhea (IBS-D) in adults this Document Dosage Form(s) Under 550 mg tablet Review REMS REMS No REMS Postmarketing Requirements Pregnancy Rating No data available on pregnant women to inform any drug associated risks. Executive Summary Efficacy Rifaximin had a small, statistically significant beneficial effect relative to placebo in global IBS symptom response using pooled data: 40.7% vs. 31.7%, with a difference of 9.0 percentage points, p < 0.001; NNT = 11. Rifaximin had a small, statistically significant beneficial effect relative to placebo in terms of the response rate for adequate relief of bloating (the key secondary efficacy measure): 40.2% vs. 30.3%, difference of 9.9 percentage points, p < 0.001; NNT = 10 (pooled results).
    [Show full text]
  • Emerging Drug List — Tegaserod Hydrogen Maleate
    Emerging Drug List CANADIAN COORDINATING OFFICE FOR HEALTH TEGASEROD HYDROGEN MALEATE TECHNOLOGY ASSESSMENT NO. 32 MAY 2002 Generic (Trade Name): Tegaserod hydrogen maleate (Zelnorm™) Manufacturer: Novartis Pharmaceuticals Indication: For the symptomatic treatment of irritable bowel syndrome with constipation (IBS-C) in female patients whose main symptoms are constipation and abdominal pain and/or discomfort. The maximum duration of treatment should be no longer than 12 weeks and the treatment should be discontinued if there has been no response after four weeks. Current Regulatory Zelnorm™ was approved by Health Canada's Therapeutic Products Directorate on Status: March 12, 2002. Launch in Canada is impending1. Description: Tegaserod is a partial agonist of 5-HT4 receptors, a new chemical class of proki- netic medications. This subclass of receptors is found throughout the gastroin- testinal tract, and it is postulated that when activated, they minimize the percep- tion of discomfort, pain and constipation associated with IBS. Tegaserod exhibits a low absolute bioavailablity after oral dosing (11%), and the time to achieve a peak concentration ranges from one to 1.3 hours.2 It is highly protein bound (98% to α1-acid glycoprotein) and its terminal half-life is 11± 5 hours. Diarrhea, abdominal pain, headache, flatulence and fatigue are the most frequently report- ed adverse events. Compared to placebo, no differences in QTc interval prolon- gations have been reported in clinical trials, although syncope (an effect seen with cisapride) has been observed at a greater frequency in tegaserod users. The recommended dosage of Zelnorm™ is 6 mg twice daily, administered prior to a meal with water.
    [Show full text]
  • Estonian Statistics on Medicines 2016 1/41
    Estonian Statistics on Medicines 2016 ATC code ATC group / Active substance (rout of admin.) Quantity sold Unit DDD Unit DDD/1000/ day A ALIMENTARY TRACT AND METABOLISM 167,8985 A01 STOMATOLOGICAL PREPARATIONS 0,0738 A01A STOMATOLOGICAL PREPARATIONS 0,0738 A01AB Antiinfectives and antiseptics for local oral treatment 0,0738 A01AB09 Miconazole (O) 7088 g 0,2 g 0,0738 A01AB12 Hexetidine (O) 1951200 ml A01AB81 Neomycin+ Benzocaine (dental) 30200 pieces A01AB82 Demeclocycline+ Triamcinolone (dental) 680 g A01AC Corticosteroids for local oral treatment A01AC81 Dexamethasone+ Thymol (dental) 3094 ml A01AD Other agents for local oral treatment A01AD80 Lidocaine+ Cetylpyridinium chloride (gingival) 227150 g A01AD81 Lidocaine+ Cetrimide (O) 30900 g A01AD82 Choline salicylate (O) 864720 pieces A01AD83 Lidocaine+ Chamomille extract (O) 370080 g A01AD90 Lidocaine+ Paraformaldehyde (dental) 405 g A02 DRUGS FOR ACID RELATED DISORDERS 47,1312 A02A ANTACIDS 1,0133 Combinations and complexes of aluminium, calcium and A02AD 1,0133 magnesium compounds A02AD81 Aluminium hydroxide+ Magnesium hydroxide (O) 811120 pieces 10 pieces 0,1689 A02AD81 Aluminium hydroxide+ Magnesium hydroxide (O) 3101974 ml 50 ml 0,1292 A02AD83 Calcium carbonate+ Magnesium carbonate (O) 3434232 pieces 10 pieces 0,7152 DRUGS FOR PEPTIC ULCER AND GASTRO- A02B 46,1179 OESOPHAGEAL REFLUX DISEASE (GORD) A02BA H2-receptor antagonists 2,3855 A02BA02 Ranitidine (O) 340327,5 g 0,3 g 2,3624 A02BA02 Ranitidine (P) 3318,25 g 0,3 g 0,0230 A02BC Proton pump inhibitors 43,7324 A02BC01 Omeprazole
    [Show full text]