DOCSLIB.ORG

Developing Novel Antisecretory Drugs to Treat Infectious Diarrhea

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Developing Novel Antisecretory Drugs to Treat Infectious Diarrhea REVIEW SPECIAL FOCUS: NEGLECTED DISEASES For reprint orders, please contact [email protected] Developing novel antisecretory drugs to treat infectious diarrhea Diarrhea, a disease of poverty and poor sanitation, kills an estimated two million children each year. Oral rehydration therapy is a very simple and inexpensive treatment that has significantly reduced mortality from secretory diarrhea caused by rotavirus, cholera and enterotoxigenic Escherichia coli. The efficacy and adoption of oral rehydration therapy would be enhanced by a drug that reduces fluid loss associated with these diseases and alleviates disease symptoms. Secretion and absorption by the intestine offer a number of potential drug targets to reduce fluid loss. Among these, the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is the most attractive because it is the primary driver of secretion in cases of diarrhea caused by enterotoxigenic bacteria. CFTR can be inhibited by both natural products and synthetic small molecules. iOWH032 is a synthetic CFTR inhibitor that has recently entered clinical trials for this indication. Diarrheal diseases are a leading killer immune and neuronal factors [7] but is beyond Eugenio L de Hostos†1, in the developing world the scope of this review. The mechanisms of Robert KM Choy1 & Every year, an estimated 2.5 billion cases of diarrhea caused by various pathogens can be Tue Nguyen1 infectious diarrhea occur among children classified as inflammatory or non-inflamma- 1Diarrheal Diseases Program, under 5 years of age [1,101], leading to the death tory. Dysentery, a typical example of an inflam- OneWorld Health, 280 Utah Avenue, Suite 250, San Francisco, of an estimated two million children. After matory, invasive diarrhea, is marked by visible CA 94080, USA respiratory infections, diarrhea is the second blood in the stools and is associated with intes- †Author for correspondence: Tel.: +1 650 392 2510 leading cause of mortality in that age group tinal damage and nutrient losses in an infected Fax: +1 650 392 2524 and kills more young children than AIDS, individual. The bacterial pathogen Shigella is the E-mail: edehostos@ oneworldhealth.org malaria and measles combined. It also causes most common cause of dysentery [8], but amoe- significant morbidity and recent studies suggest bic dysentery caused by Entamoeba histolytica that repeated bouts of diarrhea have a signifi- is a common problem in some regions [9–11]. In cant impact on cognitive development [2,3] and contrast, non-inflammatory infectious diar- malnutrition [4–6]. rheas are caused by pathogens that disrupt the Infectious diarrhea can be largely prevented absorptive and/or secretory processes of the gut by adequate sanitation and a clean water sup- epithelium without causing acute inflammation ply; aid to developing countries is, therefore, or mucosal destruction. often focused in these areas. However, much This review will focus on the development of the world’s population still lacks access to of therapeutics for non-inflammatory acute reliable supplies of clean water and/or is at watery diarrhea (AWD), or secretory diar- risk of infection when natural disasters strike. rhea. AWD can last from hours to days and Whereas increasing access to clean water is a is associated with copious fluid loss and rapid, long-term solution, there is also an immediate life-threatening dehydration. The patho- need for more effective therapies to treat infec- gens most commonly responsible for AWD tious diarrhea. Even in wealthy countries out- are rotavirus, Vibrio cholerae and entero- breaks of infectious diarrhea continue to occur, toxigenic Escherichia coli (ETEC) bacteria, although the etiology is usually different from which are associated with poor sanitation those in poorer countries, and the mortality and contaminated water in developing coun- rate is lower. tries [12–14]. There are hotspots for cholera, Diarrhea is generally classified according such as flood-prone Bangladesh, but ETEC is to the time course of the symptoms (acute or widespread and is a common cause of traveler’s chronic) and to whether the etiology is infec- diarrhea. According to the WHO, rotavirus tious or non-infectious. Non-infectious diar- is the most common cause of severe diarrhea rhea, such as that caused by irritable bowel syn- and dehydration of infants in both wealthy and drome, results from a complex interaction of developing countries. 10.4155/FMC.11.87 © 2011 Future Science Ltd Future Med. Chem. (2011) 3(10), 1317–1325 ISSN 1756-8919 1317 REVIEW | de Hostos, Choy & Nguyen Key Terms Current treatment & new effect of these drugs is mostly palliative as they do not improve rehydration, and the reduction Acute watery diarrhea: therapeutic opportunities Fluid loss due to hypersecretion In AWD due to cholera infection, the onset in discharge can mask the underlying disease. across the intestinal lumen. of diarrhea is rapid and, if left untreated, the They are contra-indicated because they can cause Rotavirus: Most common mortality rate is 50–60%, with death occurring paralytic ileus [22] and blocking discharge while cause of acute watery diarrhea, within hours to days. However, with immediate, fluid continues to accumulate in the bowel can responsible for more than appropriate treatment the mortality rate can be have lethal consequences. Furthermore, these 500,000 deaths per year. reduced to 1% [15]. Regardless of etiology, the drugs can negatively impact disease resolution Enterotoxigenic common symptom of fluid loss in cases of AWD by reducing the expulsion of bacteria. Escherichia coli: Most makes the replenishment of lost fluid by oral Although ORS salts, as well as vitamin A and common infection leading to traveler’s diarrhea, but also rehydration therapy (ORT) the cornerstone zinc supplements, are widely available, AWD causes approximately 400,000 of treatment. Oral rehydration solution (ORS) continues to kill millions. Despite its proven deaths per year. used in ORT simply consists of electrolytes efficacy, low cost and promotion by public health Cholera: Acute watery (sodium and potassium chloride) and glucose, authorities around the world, the adoption of diarrhea caused by infection which promotes water absorption and costs only ORT as the standard of care has slowed down in with the Gram-negative a few cents per treatment. Low-osmolarity ORT recent years and its use may even be declining in bacterium Vibrio cholerae. Cholera outbreaks worldwide (a slightly less concentrated and more effective many developing countries [23]. The reason for cause over 100,000 deaths version of the original ORS recipe) is actively this is still under investigation, but one postu- each year. promoted by the WHO and the United Nations lated explanation is that ORT does not provide Oral rehydration therapy: Children’s Fund, and is credited with saving mil- quick clinical relief of diarrheal symptoms (in Glucose/electrolyte solution lions of lives worldwide since its introduction in fact, during the acute phase it increases output as routinely used to treat acute watery diarrhea in the 1970s [16]. the patient rehydrates), leading to its premature developing countries. Variations to the standard ORS recipe include discontinuation. Although ORT is very effec- the use of rice water or rice syrup instead of glu- tive, its clinical and perceived efficacies could OneWorld Health: Nonprofit pharmaceutical research and cose or sucrose, which can deliver more sugar be improved by an antisecretory drug. An agent development organization that without simultaneously increasing the osmolar- that reduces enterotoxin-induced hypersecretion discovers, develops and delivers ity of the ORT [17,18]. Amylase-resistant starches used in conjunction with ORT could provide safe, effective and affordable new treatments and are also being investigated as a supplement to more rapid relief of symptoms and facilitate the interventions for people ORS because they are fermented in the colon adoption of ORT. suffering from neglected into short-chain fatty acids such as butyrate, Racecadotril (acetorphan, Bioprojet) is the diseases in the developing which stimulate local blood flow and, thus, fluid only currently marketed antisecretory drug. world, with an emphasis on diseases that disproportionately and electrolyte uptake [19]. To complement ORT, It acts by inhibiting neprilysin (enkephalin- affect children. the WHO recommends the administration of ase) and thus the degradation of enkephalin, zinc for 10 days during and after the treatment. an endogenous peptide that inhibits intestinal This treatment has been shown both to alleviate secretion [24]. Racecadotril received regulatory symptoms of diarrhea and reduce recurrence in approval in Europe and is readily available in the ensuing few months [20]. Similarly, vitamin India, but some clinical studies have called into A supplementation during early childhood has question its efficacy [25,26] and as a result it has been shown to improve prognosis and reduce not been widely adopted. For the past 4 years, mortality due to diarrhea and is being promoted OneWorld Health (OWH) has been developing by the WHO [21]. a novel antisecretory compound that targets an Acute watery diarrhea usually resolves on its ion channel that is critical for AWD. own as long as adequate hydration is maintained but in certain cases when specific pathogens are Targeting the cystic fibrosis identified (e.g.,V. cholerae), antibiotics are used transmembrane in addition to ORS to speed
Load more

Recommended publications
  • FDA Warns About an Increased Risk of Serious Pancreatitis with Irritable Bowel Drug Viberzi (Eluxadoline) in Patients Without a Gallbladder
    FDA warns about an increased risk of serious pancreatitis with irritable bowel drug Viberzi (eluxadoline) in patients without a gallbladder Safety Announcement [03-15-2017] The U.S. Food and Drug Administration (FDA) is warning that Viberzi (eluxadoline), a medicine used to treat irritable bowel syndrome with diarrhea (IBS-D), should not be used in patients who do not have a gallbladder. An FDA review found these patients have an increased risk of developing serious pancreatitis that could result in hospitalization or death. Pancreatitis may be caused by spasm of a certain digestive system muscle in the small intestine. As a result, we are working with the Viberzi manufacturer, Allergan, to address these safety concerns. Patients should talk to your health care professional about how to control your symptoms of irritable bowel syndrome with diarrhea (IBS-D), particularly if you do not have a gallbladder. The gallbladder is an organ that stores bile, one of the body’s digestive juices that helps in the digestion of fat. Stop taking Viberzi right away and get emergency medical care if you develop new or worsening stomach-area or abdomen pain, or pain in the upper right side of your stomach-area or abdomen that may move to your back or shoulder. This pain may occur with nausea and vomiting. These may be symptoms of pancreatitis, an inflammation of the pancreas, an organ important in digestion; or spasm of the sphincter of Oddi, a muscular valve in the small intestine that controls the flow of digestive juices to the gut. Health care professionals should not prescribe Viberzi in patients who do not have a gallbladder and should consider alternative treatment options in these patients.
    [Show full text]
  • A 0.70% E 0.80% Is 0.90%
    US 20080317666A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0317666 A1 Fattal et al. (43) Pub. Date: Dec. 25, 2008 (54) COLONIC DELIVERY OF ACTIVE AGENTS Publication Classification (51) Int. Cl. (76) Inventors: Elias Fattal, Paris (FR); Antoine A6IR 9/00 (2006.01) Andremont, Malakoff (FR); A61R 49/00 (2006.01) Patrick Couvreur, A6II 5L/12 (2006.01) Villebon-sur-Yvette (FR); Sandrine A6IPI/00 (2006.01) Bourgeois, Lyon (FR) (52) U.S. Cl. .......................... 424/1.11; 424/423; 424/9.1 (57) ABSTRACT Correspondence Address: Drug delivery devices that are orally administered, and that David S. Bradlin release active ingredients in the colon, are disclosed. In one Womble Carlyle Sandridge & Rice embodiment, the active ingredients are those that inactivate P.O.BOX 7037 antibiotics, such as macrollides, quinolones and beta-lactam Atlanta, GA 30359-0037 (US) containing antibiotics. One example of a Suitable active agent is an enzyme Such as beta-lactamases. In another embodi ment, the active agents are those that specifically treat colonic (21) Appl. No.: 11/628,832 disorders, such as Chrohn's Disease, irritable bowel syn drome, ulcerative colitis, colorectal cancer or constipation. (22) PCT Filed: Feb. 9, 2006 The drug delivery devices are in the form of beads of pectin, crosslinked with calcium and reticulated with polyethylene imine. The high crosslink density of the polyethyleneimine is (86). PCT No.: PCT/GBO6/OO448 believed to stabilize the pectin beads for a sufficient amount of time such that a Substantial amount of the active ingredi S371 (c)(1), ents can be administered directly to the colon.
    [Show full text]
  • 1This Action Arises Under the Patent Laws of the United States. See 35 U.S.C
    IN THE UNITED STATES DISTRICT COURT FOR THE EASTERN DISTRICT OF PENNSYLVANIA MCNEIL-PPC, INC., : Plaintiff, : CIVIL ACTION : v. : : L. PERRIGO COMPANY, : and PERRIGO COMPANY, : No. 01-1100 Defendants. : OPINION AND ORDER SCHILLER, J. June , 2002 This is a patent infringement action. Plaintiff McNeil-PPC, Inc. (“McNeil”) alleges Defendants L. Perrigo Company and Perrigo Company (collectively “Perrigo”) infringe four McNeil patents covering a popular version of the Imodium® Advanced antidiarrheal. In a Memorandum and Order issued April 3, 2002, I construed certain disputed claim terms pursuant to Markman v. Westview Instruments, Inc. , 517 U.S. 370 (1996). Beginning April 22, 2002, this matter was tried without a jury, and I enter the following Findings of Fact and Conclusions of Law as required by Rule 52(a) of the Federal Rules of Civil Procedure. 1 FINDINGS OF FACT I. BACKGROUND This action pits a manufacturer of national brand pharmaceuticals against its competitor, a generic drug manufacturer. Four patents owned by Plaintiff McNeil are at issue in this case: United States Patents 5,248,505 (“the ’505 patent”)(PTX1) and 5,612,054 (“the ’054 patent”)(PTX2) are 1This action arises under the patent laws of the United States. See 35 U.S.C. § 271(e)(2) and 21 U.S.C. § 355(j). Jurisdiction is based on 28 U.S.C. §§ 1331 and 1338(a). Venue is proper in this Court pursuant to 28 U.S.C. §§ 1391(c) and 1400(b). referred to as “the Garwin patents”; 2 United States Patents 5,679,376 (“the ’376 patent”)(PTX3) and 5,716,641 (“the ’641 patent”)(PTX4) are referred to as “the Stevens patents.” A.
    [Show full text]
  • World Journal of Pharmaceutical Research Yashasvi Et Al
    World Journal of Pharmaceutical Research Yashasvi et al . World Journal of Pharmaceutical SJIF Research Impact Factor 6.805 Volume 6, Issue 1, 998-1004. Research Article ISSN 2277– 7105 EFFICACY OF RACECADOTRIL COMPARED TO DIPHENOXYLATE IN ACUTE RADIATION ENTERITIS Dr. Yashasvi Suvarna*, Dr. Janaki M. G. and Dr. M. C. Shivamurthy Departments of Pharmacology and Radiation Oncology, M S Ramaiah Medical College and Hospitals, Bangalore. ABSTRACT Article Received on 08 Nov. 2016, Introduction: Radiation enteritis is one of the most common and Revised on 28 Nov. 2016, distressing complications of pelvic radiation. There are limited studies Accepted on 18 Dec. 2016 DOI: 10.20959/wjpr20171-7629 that have assessed the efficacy of antidiarrhoeals in radiation enteritis. This study was done to assess the efficacy of racecadotril versus diphenoxylate in acute radiation enteritis. Methods: This was a *Corresponding Author Dr. Yashasvi Suvarna prospective open label randomized study.50 patients were recruited Departments of into the study with 25 patients in each group. They received either Tab. Pharmacology and Racecadotril 100mg tid for 3 days or Tab. Diphenoxylate Radiation Oncology, M S Hydrochloride 2.5 mg(+ atropine 0.025 mg) tid for 3 days as an add on Ramaiah Medical College and Hospitals, Bangalore. to fluid supplementation. Results: The grade of radiation enteritis in both the groups were similar after 3 days of treatment with the drug (p=0.210).Only one patient in the racecadotril group required cessation of pelvic radiation due to hypokalemia. Conclusion: Racecadotril and diphenoxylate are both effective in treating radiation enteritis and are well tolerated. Further studies with racecadotril are warranted.
    [Show full text]
  • Narcotic Analgesics I Blanton SLIDE 1: We Will Be Spending the Next 90 Minutes Discussing Narcotic Analgesics- That Is Morphine, Oxycodone, Heroin, Etc
    Narcotic Analgesics I Blanton SLIDE 1: We will be spending the next 90 minutes discussing narcotic analgesics- that is morphine, oxycodone, heroin, etc. These drugs act primarily thru the opiate receptor system. I always like to begin by presenting two factoids that I believe illustrate the power of this system: (1) Ok imagine you are in pain! Now I tell you that I am going to give you an injection of morphine or heroin. Even if I instead give you an injection of just saline- 50% of you will report that your pain is significantly reduced- that is quite a placebo effect. However, if instead of saline I give you an injection of Naloxone, an opiate receptor antagonist- the placebo effect is eliminated. In other words you are activating your opiate receptor system to induce analgesia. (2) acupuncture can be used to reduce pain. However, Naloxone will block this effect- in otherwords the acupuncture is activating your opiate receptor system. SLIDE 1A: The use of narcotic analgesics for effective pain management has certainly had its flip side……. With prescription narcotic analgesics helping to fuel the current heroin epidemic…. Back to SLIDE 1: So narcotic analgesics. The name narcotic is somewhat misleading, because it implies narcosis or somnolence. The name opiate or opioid is more precise because it connotes analgesia, without causing sleep or loss of consciousness. SLIDE 2: The terms opiate or opioid, as you are probably aware, refers to opium, the crude extract of the Poppy plant, Papaver somniferum. Opium comes from the seed pod of the plant after the petals have dropped.
    [Show full text]
  • The Prevention and Treatment of Drug Misuse in Britain
    If you have issues viewing or accessing this file contact us at NCJRS.gov. .. " FW The prevention and treatment of drug misuse in Britain "I Issued by Rererence Division BRITISH INFORMATION SERVICES All Agency of the British Government 845 THIRD AVENUE, NEW YORK, N.Y. ]0022 This material is prepared, edited, issued or circulated by British Information Servic(!s, 845 Third Avenue, New York, N. Y.l0022, which is registered under the Foreign Agents Registration Act as an agent of the Brilish Government. This material is filed with the Department of Justice where the required registration statement is available for public inspection. Registration does not indicate approval 0/ the contents of this material by the United States Government. PRINTED IN ENGLAND BY TRADE UNION LABOR BY COLUNS AND WILSON LTD., ANDOVER The prevention and treatment of drug misuse in Britain Prepared by REFERENCE DIVISION CENTRhL OFFICE OF INFORMATION, LONDON Oclo~'er 1978 Quote No RS94S/78 CLASSIFICATION 4(c) N.B.-This pamphlet is i//tellded to be used for referellce purposes alld may be freely used ill preparing articles, speeches, broadcasts, elc. No acknowledgment is necessary. Please Ilote the date ofpreparation. Tire text gives general gUidance only, and should 1I0t be treated as an authoritative statement of the law. Pamphlets ill this series may be obtained from the Tllformation Office at tlte British Embassy, Consulate or High Commission in tile inquirer's Co/lIltl'Y of residellce. CONTENTS Page INTRODUCTION 1 BACKGROUND .. 3 PREVENTING DRUG MISUSE 8 The Law 8 Health Education 17 TREATMENT AND REHABILITATION .. 20 Narcotic Drug Misuse and the Role of the Clinics 20 Treating Other Forms of Drug Misuse 26 Rehabilitation 26 INFORMATION AND RESEARCH ., 29 APPENDICES 1.
    [Show full text]
  • Opioid Analgesics and the Gastrointestinal Tract
    NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #64 Carol Rees Parrish, R.D., M.S., Series Editor Opioid Analgesics and the Gastrointestinal Tract Lingtak-Neander Chan Opioids have been used to manage pain and other ailments for centuries. The consti- pating effects of opioid analgesic agents are well known and can be used to manage severe diarrhea and control high output ostomies. Loperamide, diphenoxylate, and difenoxin are currently the only opioid-derivatives approved by the FDA for treating diarrhea. Drug-drug interactions and end organ dysfunction may exacerbate systemic side effects of these drugs. In patients who have failed to respond to these agents, other systemic opioids may be considered. The goal of therapy to control gastrointestinal secretion should be to use the lowest effective dose with minimal side effects. Careful monitoring for systemic side effects during the initiation and dose titration phase are crucial to minimize the risks associated wtih opioid use. INTRODUCTION Sumerian clay tablets inscribed in Cuneiform script he term “opioid” refers to a large group of com- about 3000 B.C. Opium was probably used as an pounds and chemicals that share the characteris- euphoriant in religious rituals by the Sumerians (1,2). Ttics of opium. Opium, from the Greek word During the Middle Ages, after opium was introduced “opos” for juice, refers to the liquid collected from the to Asia and Europe, more extensive documentation of unripe seed capsule of Papaver somniferum L., also opium use became available. It wasn’t until 1805, that known as opium poppy. Opium has been used for med- a young German apothecary named Friedrich Wilhelm icinal purposes for centuries.
    [Show full text]
  • New Drug Evaluation Monograph Template
    © Copyright 2012 Oregon State University. All Rights Reserved Drug Use Research & Management Program Oregon State University, 500 Summer Street NE, E35 Salem, Oregon 97301-1079 Phone 503-947-5220 | Fax 503-947-1119 Class Review: Antidiarrheals Date of Review: January 2017 Purpose for Class Review: To identify appropriate utilization management strategies for drugs used to treat diarrhea. Research Questions: 1. What is the comparative efficacy and effectiveness for bismuth subsalicylate, loperamide, diphenoxylate/atropine, paregoric, crofelemer, or opium tincture in management of diarrhea? 2. What are the comparative harms or potential abuses for bismuth subsalicylate, loperamide, diphenoxylate/atropine, paregoric, crofelemer, or opium tincture? 3. Are there subgroups of patients based on demographics (age, racial or ethnic groups and gender), other medications, or co-morbidities for which one treatment for diarrhea is more effective or associated with fewer adverse events? Conclusions: There is insufficient comparative evidence of efficacy and effectiveness between bismuth subsalicylate, loperamide, diphenoxylate/atropine, paregoric, crofelemer and opium tincture. Moderate quality evidence shows that the addition of loperamide to ciprofloxacin for treatment of traveler’s diarrhea may decrease the duration of diarrhea within the first 24 to 48 hours of symptom onset.1 Opium tincture has not been evaluated by the United States Food and Drug Administration (FDA) for safety and effectiveness because it was marketed before 1962.2 The FDA
    [Show full text]
  • Citation Classics and Trends in the Field of Opioids: a Bibliometric Analysis
    Open Access Original Article DOI: 10.7759/cureus.5055 Citation Classics and Trends in the Field of Opioids: A Bibliometric Analysis Hira F. Akbar 1 , Khadijah Siddiq 2 , Salman Nusrat 3 1. Internal Medicine, Dow Medical College, Dow University of Health Sciences, Karachi, PAK 2. Internal Medicine, Civil Hospital Karachi, Dow University of Health Sciences, Karachi, PAK 3. Gasteroenterology, University of Oklahoma Health Sciences Center, Oklahoma City, USA Corresponding author: Hira F. Akbar, [email protected] Abstract Introduction Bibliometric analysis is one of the emerging and latest statistical study type used to examine and keep a systemic record of the research done on a particular topic of a certain field. A number of such bibliometric studies are conducted on various topics of the medical science but none existed on the vast topic of pharmacology - opioids. Hence, we present a bibliometric analysis of the ‘Citation Classics’ of opioids. Method The primary database chosen to extract the citation classics of opioids was Scopus. Top 100 citation classics were arranged according to the citation count and then analyzed. Results The top 100 citation classics were published between 1957 and 2013, among which seventy-two were published from 1977 to 1997. Among all nineteen countries that contributed to these citation classics, United States of America alone produced sixty-three classics. The top three journals of the list were multidisciplinary and contained 36 citation classics. Endogenous opioids were the most studied (n=35) class of opioids among the citation classes and the most studied subject was of the neurosciences. Conclusion The subject areas of neurology and analgesic aspects of opioids are well established and endogenous and synthetic opioids were the most studied classes of opioids.
    [Show full text]
  • Racecadotril (Hidrasec) for Acute Diarrhoea June 2012
    Racecadotril (Hidrasec) for acute diarrhoea June 2012 This technology summary is based on information available at the time of research and a limited literature search. It is not intended to be a definitive statement on the safety, efficacy or effectiveness of the health technology covered and should not be used for commercial purposes. The National Horizon Scanning Centre Research Programme is part of the National Institute for Health Research June 2012 Racecadotril (Hidrasec) for acute diarrhoea Target group • Acute diarrhoea: infants (older than 3 months), children and adults – add on to oral rehydration therapy. Technology description Racecadotril (Acetorphan; Hidrasec) is an antisecretory enkephalinase inhibitor. It is the racemic mixture of the enantiomers dexecadotril (retorphan) and ecadotril (sinorphan). Racecadotril inhibits the degradation of endogenous enkephalins, which reduces the hypersecretion of water and electrolytes into the intestinal lumen1. Racecadotril exerts its antidiarrhoeal action without modifying the duration of intestinal transit. Racecadotril is administered at 1.5mg/kg three times daily for infants and children, and 60mg three times daily for adults, for a maximum of 7 days. Innovation and/or advantages If licensed, racecadotril would represent the first in a new class of treatments for this patient group. Developer Abbott Healthcare Products Ltd (Licensee); Bioprojet Europe Ltd. NHS or Government priority area This topic is relevant to The National Service Framework for Child Health and Maternity (2004). Relevant guidance • NICE clinical guideline. Diarrhoea and vomiting in children: Diarrhoea and vomiting caused by gastroenteritis: diagnosis, assessment and management in children younger than 5 years. 20092. Clinical need and burden of disease Severe diarrhoea can quickly cause dehydration and become a life-threatening condition2.
    [Show full text]
  • Viberzi™ (Eluxadoline) – Safety Update
    Viberzi™ (eluxadoline) – Safety update • On March 15, 2017, the FDA announced that Allergan’s Viberzi (eluxadoline) should not be used in patients who do not have a gallbladder. • Patients who do not have a gallbladder who are taking Viberzi for irritable bowel syndrome with diarrhea (IBS-D) have an increased risk of developing pancreatitis, sphincter of Oddi spasm, and death. • Symptoms of pancreatitis have occurred with just one or two doses of Viberzi at the recommended dosage for patients who do not have a gallbladder (75 mg) and who do not consume alcohol. • Viberzi is a schedule IV controlled substance indicated in adults for the treatment of IBS-D. — IBS-D affects the large intestine and causes cramping, abdominal pain, bloating, gas, and diarrhea. Viberzi works by decreasing bowel contractions, which leads to less diarrhea. • Healthcare providers should not prescribe Viberzi to patients who do not have a gallbladder and should consider alternative over-the-counter (OTC) or prescription medicines indicated to treat IBS- D and its related symptoms in these patients. — OTC examples include bismuth subsalicylate (eg, Kaopectate®, Pepto-Bismol™), Imodium® (loperamide) and Gas-X® (simethicone). Prescription Lomotil® (diphenoxylate/atropine) may be used to treat diarrhea. — Other prescription medications indicated to treat IBS-D include Lotronex® (alosetron) and Xifaxan® (rifaximin). — Refer to individual drug labels for specific indication information. • Patients should stop taking Viberzi right away and seek immediate emergency care if they experience symptoms of pancreatitis or spasm of the sphincter of Oddi, such as new or worsening abdominal pain, or pain in the upper right side of the abdomen that radiates to the back or shoulder.
    [Show full text]
  • DIPHENOXYLATE HYDROCHLORIDE and ATROPINE SULFATE- Diphenoxylate Hydrochloride and Atropine Sulfate Tablet Aphena Pharma Solutions - Tennessee, LLC
    DIPHENOXYLATE HYDROCHLORIDE AND ATROPINE SULFATE- diphenoxylate hydrochloride and atropine sulfate tablet Aphena Pharma Solutions - Tennessee, LLC ---------- DESCRIPTION Each tablet for oral administration contains: diphenoxylate hydrochloride, USP 2.5 mg (Warning – May be habit forming) atropine sulfate, USP 0.025 mg Diphenoxylate hydrochloride, an antidiarrheal, is ethyl 1-(3-cyano-3, 3-diphenylpropyl)-4-phenyl- isonipecotate monohydrochloride and has the following structure: Atropine sulfate, an anticholinergic, is endo-(±)-alpha-(hydroxymethyl) benzeneacetic acid 8-methyl-8- azabicylo[3.2.1] oct-3-yl ester sulfate (2:1)] (salt) monohydrate and has the following structure: A subtherapeutic amount of atropine sulfate is present to discourage deliberate overdosage. Each tablet for oral administration contains the following inactive ingredients: colloidal silicon dioxide, microcrystalline cellulose, pregelatinized starch and stearic acid. CLINICAL PHARMACOLOGY Diphenoxylate is rapidly and extensively metabolized in man by ester hydrolysis to diphenoxylic acid (difenoxine), which is biologically active and the major metabolite in the blood. After a 5 mg oral dose of carbon-14 labeled diphenoxylate hydrochloride in ethanolic solution was given to three healthy volunteers, an average of 14% of the drug plus its metabolites was excreted in the urine and 49% in the feces over a 4-day period. Urinary excretion of the unmetabolized drug constituted less than 1% of the dose, and diphenoxylic acid plus its glucuronide conjugate constituted about 6% of the dose. In a 16 subject cross-over bioavailability study, a linear relationship in the dose range of 2.5 mg to 10 mg was found between the dose of diphenoxylate hydrochloride (given as Diphenoxylate Hydrochloride and Atropine Sulfate Oral Solution) and the peak plasma concentration, the area under the plasma concentration-time curve, and the amount of diphenoxylic acid excreted in the urine.
    [Show full text]