Diphenoxylate Hydrochloride, a Schedule

Total Page:16

File Type:pdf, Size:1020Kb

Diphenoxylate Hydrochloride, a Schedule CASE REPORTS studies of brown recluse spider venom. Infect Immunol 10:1412, shown capable of producing a morphine-like Dec 1974 17. Denny WF, Dilltha CJ, Morgan PN: Hemotoxic effect of euphoria.4 Morphine-like addiction is also theo- Loxosceles recluses venom: In vivo and in vitro studies. J Lab Clin Med 64:291-298, Aug 1964 retically possible following prolonged use of the 18. Hershey FB, Aulenbacher CE: Surgical treatment of brown recluse bites. Ann Surg 170:300, Aug 1969 drug at high doses. 19. Russell FE, Wainschel J, Gertsch WJ: Bites of spiders and other arthropods. Cufr Ther 864-867, 1974 Recently, I encountered a case of deliberate 20. Berger RS: A critical look at therapy for the brown re- cluse spider bite. Arch Dermatol 107:298, 1973 abuse of diphenoxylate hydrochloride, and ord- ered a computer search of the literature for fur- ther information. Considering the frequency with which this drug is prescribed, its schedule V rat- Refer to: Rubinstein JS: Deliberate abuse of diphenoxylate hy- drochloride, a schedule V narcotic. West J Med 1-31: ing, and the great demand among abusers for its 148-150, Aug 1979 opiate congeners, it was surprising to discover that deliberate abuse of diphenoxylate hydro- chloride for its subjective effects has never been Deliberate Abuse of reported in the literature. Diphenoxylate Report of a Case Hydrochloride, a Schedule A 32-year-old man came to the psychiatric outpatient clinic with complaints of anxiety and V Narcotic depression over his inability to carry out his duties JONATHAN S. RUBINSTEIN, MD satisfactorily at work. California The patient had a long history of drug abuse, Beverly Hills, including the intravenous abuse of heroin, and at DIPHENOXYLATE is a meperidine congener fre- age 24 had been admitted to hospital for what he quently prescribed in the treatment of diarrhea. described as an inadvertent overdose. Following The drug is available in both tablet and liquid this experience he became "more cautious" in his form (Lomotil, Colonil); each tablet and each 5 use of drugs, resolved to stop using heroin; the ml dose of the liquid contains 2.5 mg of diphen- patient broke all contact with the street scene, oxylate hydrochloride and 0.025 mg of atropine but continued to abuse pills, in particular bar- sulfate. Diphenoxylate hydrochloride is a schedule biturates, as well as prescription opiates such as V narcotic.' pentazocine and propoxyphene. In addition, the The chemical structure of diphenoxylate hydro- patient related that he had, over the past year, chloride is similar to that of meperidine,2 and the begun to abuse diphenoxylate hydrochloride, tak- drug carries many of the risks and hazards char- ing large doses of the drug intermittently, but acteristic of the opiates. Mild side effects include never more than once or twice a week for periods drowsiness, rash, dizziness, depression and nausea. of up to several weeks at a time. Treatment of overdose or individual hypersensi- The patient's first experience with the drug had tivity reaction is simUar to that for meperidine or been with a prescription given to his wife by morphine intoxication. Prolonged monitoring of her doctor as prophylaxis before an intended trip the patient is essential because, although there abroad. He had found the bottle of pills and, might be an initial response to narcotic antagon- not being familiar with the drug, had looked it up ists, life-threatening respiratory depression may in the Physicians' Desk Reference. He had learned occur as late as 30 hours following ingestion.2 that it was an opiate and, in large doses, could Several cases of accidental overdose in chiIkpfn produce opiate-like effects. The patient enjoyed have been reported.3 the sensation, and then began taking the drug As with other opiates, the drug also has a regularly. He found that most physicians would potential for abuse. Though at therapeutic ranges issue a prescription for diphenoxylate hydrochlo- (20 mg of diphenoxylate hydrochloride per day ride with little question when he complained of or less, in divided doses) opioid effects do not diarrhea, even when he would specifically request occur, doses of 40 to 60 mg at a time have been the drug by name. On several occasions he in- formed the physician that he was about to em- Dr. Rubinstein is a third-year resident in psychiatry at the Olive View Medical Center, Sylmar, California. bark on an extended trip abroad, and received Submitted December 6, 1978. large supplies of the drug. The patient would Reprint requests to: Jon Rubinstein, MD, 14445 Olive View Dr., Sylmar, CA 91342. ordinarily take 60 to 100 tablets for the desired 148 AUGUST 1979 * 131 * 2 CASE REPORTS effect, which he described as a euphoria qualita- appraising the extent to which the drug is being tively similar to that produced by other orally abused. The relatively high cost of the medica- taken opiates. Concomitant ingestion of alcohol tion, even when obtained through licit channels, or other drugs seemed to result in potentiation as well as the fact that diphenoxylate hydrochlo- of the effects. ride even as a salt is virtually insoluble in water5 On one occasion the patient shared a quantity and therefore cannot be abused parenterally, may of the drug with a friend who reported experienc- be contributory. This by no means, however, ing a similar high. The patient did not report obviates the possibility that deliberate abuse of having been bothered by any adverse atropinic the drug, though hitherto unreported, may be side-effects at his usual dosage. The largest single widespread. At present I am collecting and docu- amount he ever took was about 140 tablets; at menting a more extensive series of cases. this dosage he did experience pronounced dryness It has been stated that subtherapeutic amounts of the mouth, and woke up the following morning of atropine sulfate have been added to the com- with nausea and a severe headache. Though his pound to discourage deliberate overdosage2 (P 1449) euphoria at the higher dosage was significantly This contention seems to conflict, however, with enhanced, the patient says he ordinarily restricts experimental data. Doses of less than 2 mg of his dosage of the drug for several reasons: ( 1 ) He atropine are, in an adult, unlikely to produce any is afraid of damaging his gastrointestinal tract, clinically significant dysphoric effects.6 Therefore, (2) he conscientiously wishes to avoid addiction even 60 tablets, which is a quantity significantly and (3) the cost of the drug, even when pur- beyond that which is theoretically required to chased at a pharmacy (as opposed to the street produce a morphine-like euphoria, would not price), is fairly expensive. contain a sufficient amount of atropine sulfate to disturb the patient sufficiently, presumably, to Discussion discourage deliberate overdosage. This is par- That this drug is abused is not either astonish- ticularly true because many opiate abusers are ing or remarkable; any medication-no matter characteristically willing to tolerate considerable how ostensibly innocuous-carries with it the amounts of distress to obtain their high, "paying potential for abuse. What is remarkable is the the price" not only in physical discomfort, but ease with which this drug, a narcotic, is obtained, often, ultimately, in the typical, erosive, down- and the apparent willingness of many physicians ward-spiral of the addicts' life-style. to issue prescriptions to a patient with little or The case reported here raises a number of no question. questions. Clearly, there is a need for a height- Many physicians seem unaware either of the ened level of awareness among physicians con- opioid pharmacological structure of diphenoxylate cerning the pharmacological nature of the sub- hydrochloride or of its consequent potential for stance and its potential hazards, including the abuse and dependency. An informal survey I possibility of deliberate abuse and of habituation. conducted among physicians at two academic Certainly a greater index of suspicion should be centers seems to confirm this. Of 20 physicians exercised when prescribing this medication for interviewed (all of whom stated they prescribed patients with histories of drug abuse, those who the drug "at least occasionally," and some said specifically request the drug by name and especi- they did so "often") only six were aware of the ally those patients who express a desire for inor- pharmacological structure of the medication and dinately large quantities of the medication. In of its potential for abuse. Ironically, in our case addition, one must question the clinical sagacity report the patient apparently had made more of prescribing a narcotic-containing compound assiduous use of the Physicians' Desk Reference, for any patient with diarrhea before potentially for his own purposes than had the prescribing less hazardous drugs have been given an adequate physician. trial. There is, unquestionably, no paucity of The absence of previous case reports is puzzling. nonnarcotic medications, many of proven efficacy The patient's statement regarding the enthusiastic as well as safety, available on the market today. reaction of his friend to the drug suggests that his experience is neither idiosyncratic nor unique, Summary though the patent's lack of contact with the Diphenoxylate hydrochloride is a drug fre- street scene renders him incapable of accurately quently prescribed in the treatment of diarrhea. THE WESTERN JOURNAL OF MEDICINE 149 CASE REPORTS Though it is chemically related to meperidine, Report of a Case deliberate abuse or dependency on this drug has In a 16-year-old girl with stage IV non- never been reported. A case is presented in which Hodgkin lymphoma in relapse despite multiple the patient had been using the drug regularly, in chemotherapy regimens, increasing sore throat, large doses, for its morphine-like euphoriant ef- fever and dysphagia developed.
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]