DOCSLIB.ORG

021879Orig1s000

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 021879Orig1s000 PHARMACOLOGY REVIEW(S) MEMORANDUM DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service Food and Drug Administration ________________________________________________________________________ Division of Neurology Products (HFD-120) Center for Drug Evaluation and Research Date: October 29, 2010 From: Lois M. Freed, Ph.D. Supervisory Pharmacologist Subject: NDA 21-879 (Nuedexta; dextromethorphan plus quinidine); SDN 38, dated April 23, 2010 (received April 30, 2010). ________________________________________________________________________ Nuedexta™ (formerly Neurodex™, Zenvia™) is a combination drug product intended for the treatment of pseudobulbar affect (PBA) in patients with amyotrophic lateral sclerosis or multiple sclerosis. Nuedexta contains dextromethorphan hydrobromide and quinidine sulfate, two marketed drugs. NDA 21-879 was originally submitted by the sponsor (Avanir Pharmaceuticals) on January 27, 2006 (received January 30, 2006). The nonclinical data provided in support of that application were reviewed by Dr. Kathleen Young (Pharmacology/Toxicology Review and Evaluation, NDA 21-879, Kathleen Young, Ph.D., October 30, 2006). An Approvable letter was sent to the sponsor on October 30, 2006, without draft labeling. Deficiencies precluding approval were clinical (both safety and efficacy); however, a number of nonclinical comments were communicated to the sponsor: • Potential deficiencies (e.g., lack of adequate high dose) in the fertility and early embryonic development, embryofetal development, and pre-and post-natal development studies in rat and the embryofetal development study in rabbit. • The lack of a chronic toxicology study in non-rodent. • The need to conduct a juvenile neurotoxicology study in an appropriate animal species to assess the potential for [Nuedexta] to induce apoptotic neurodegeneration during development. • The ongoing 2-year carcinogenicity study in rat should be submitted as soon as possible. The sponsor submitted nonclinical data to IND 56954 (dextromethorphan/quinidine for PBA) in response to these comments. These data were reviewed by Dr. D. Charles Thompson (Preliminary Pharmacology/Toxicology IND Safety Evaluation, IND 56,954, D. Charles Thompson, R.Ph, Ph.D., 5/7/2009) and comments were sent to the sponsor on 7/22/2009: Reference ID: 2856942 1 • The new nonclinical data adequately justified the high dose used in the original rat fertility and early embryonic development (to implantation) and embryofetal development studies, so those studies would not need to be repeated. However, the pre- and post-natal development study, conducted using a lower high-dose, will need to be repeated using the same high dose used in the original fertility and embryofetal studies. In addition, due to differences in the degree of maternal toxicity between studies, the pre- and post-natal study should include a teratology examination. • The embryofetal development study in rabbit will need to be repeated. The sponsor was informed in preliminary responses to a Type C meeting request (sent 11/9/2009; meeting cancelled by the sponsor) that a pre- and post-natal development study in rat and an embryofetal development study in rabbit would be needed, but may be submitted post-approval. However, based on additional information submitted by the sponsor, the repeat pre- and post-natal evaluation would not need to include a teratology evaluation. In the Complete Response, the sponsor submitted the following nonclinical studies: • In vitro hERG assay of AVP-923 (dextromethorphan [DM]/quinidine [Q]) in HEK293 cells. • In vitro effects of quinidine sulfate on ECG parameters in the rabbit left ventricular wedge preparation. • In vivo 7-day PK study of DM/Q in Beagle dog • In vitro metabolism studies in human liver preparations • Toxicology o 5-week dose-ranging study of DM/Q in Beagle dog o 39-week oral toxicity study of DM/Q in Beagle dog o 24-month carcinogenicity study of DM/Q in rat All of these studies, with the exception of the in vitro metabolism studies (to be reviewed by the Clinical Pharmacology team), were reviewed by Dr. Thompson (Pharmacology/Toxicology NDA Review and Evaluation, NDA 21-879, D. Charles Thompson, R.Ph, Ph.D., 10/1/2010). Based on his review, Dr. Thompson has concluded that the nonclinical studies submitted are adequate to support approval of Nuedexta for the intended indication, with the following nonclinical studies to be conducted as postmarketing requirements (PMRs): • Juvenile neurotoxicology study in rat. • Pre- and post-natal development study in rat • Embryo-fetal development study in rabbits. Dr. Thompson notes that the sponsor has committed to conducting these studies post- approval, and has suggested time lines for the conduct and submission of these studies. Reference ID: 2856942 2 Comments: I concur with Dr. Thompson’s conclusion and recommendations. I would also recommend, as a postmarketing requirement (PMR), a juvenile animal toxicology study in one species (rat) to support the PMR for a pediatric study. One additional issue needs to be addressed. According to a recent published study (Huang X-P et al. Mole Pharm 76(4):710-722, 2009, discussed in Elangbam CS Tox Path 000:1-12, 2010 online), quinidine has been identified as a 5HT2B agonist. According to Huang et al. (2009), these are the first data to demonstrate this effect of quinidine. (Huang et al. (2009) did not identify dextromethorphan as a 5HT2B agonist; the sponsor did not assess either quinidine or dextromethorphan for binding or activity at the 5HT2B receptor.) 5HT2B agonist activity is considered a potential cause of drug-induced cardiac valvulopathy. A number of drugs reported to induce valvular heart disease (VHD) in humans, including some that have been removed from the market due to a documented association with VHD (pergolide, fenfluramine, and dexfenfluramine), have been demonstrated to be potent 5HT2B agonists (cf. Frachon I et al. PLoS One 5(4):1-5, 2010; Roth BL NEJM 356(1):6-9, 2007; Zanettini R et al. NEJM 356(1):39-46, 2007). To my knowledge, there have been no published reports of VHD in humans caused by quinidine, although quinidine has been marketed for many years as a Class 1a antiarrhythmic at substantially higher doses. It is possible, however, that treatment may be longer in duration in patients with PBA, and duration of treatment is reported to be an important risk factor for drug-induced VHD (cf. Roth, 2007; Shade et al. NEJM 356(1):29-38, 2007). No effects on cardiac valves were observed in the toxicity studies of DM/Q; however, at least in the rodent, histopathological evaluation of cardiac valves is commonly absent. Therefore, the lack of reported valvular effects in the toxicity studies of DM/Q does not rule out the potential for quinidine to induce valvulopathy. Since 5HT2B agonist activity has been reported only in a single published study, the sponsor should be given the opportunity to confirm this pharmacodynamic effect, i.e., by conducting studies to assess the in vitro binding affinity and functional activity of quinidine at the 5HT2B receptor. If these studies confirm that quinine is a 5HT2B agonist, an investigative study should be conducted to assess the potential for quinidine to induce cardiac valvulopathy. Depending on the results of these studies, it may also be necessary for a focused examination of cardiac valves to be incorporated into the juvenile animal toxicology study to be conducted post-approval. This issue can be addressed when the juvenile study protocol is submitted for review. Therefore, I would recommend that studies to investigate the binding affinity and functional activity of quinidine at the 5HT2B receptor and, if necessary, a follow-up investigative study to assess the potential for quinidine to induce cardiac valvulopathy be an additional PMR. 3 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately following this page Reference ID: 2856942 3 --------------------------------------------------------------------------------------------------------- This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature. --------------------------------------------------------------------------------------------------------- /s/ ---------------------------------------------------- LOIS M FREED 10/29/2010 Reference ID: 2856942 DEPARTMENT OF HEALTH AND HUMAN SERVICES PUBLIC HEALTH SERVICE FOOD AND DRUG ADMINISTRATION CENTER FOR DRUG EVALUATION AND RESEARCH PHARMACOLOGY/TOXICOLOGY NDA REVIEW AND EVALUATION Application number: 21-879 Supporting document/s: 38 Applicant’s letter date: 23 April 2010 CDER stamp date: 30 April 2010 Product: Zenvia™ (Dextromethorphan/Quinidine; formerly Neurodex™) Indication: Treatment of Pseudobulbar Affect occurring in ALS, MS, stroke, and Alzheimer’s Disease Applicant: Avanir Pharmaceuticals, Inc. 101 Enterprise, Suite 300 Aliso Viejo, CA 92656 Review Division: Neurology Products, HFD-120 Reviewer: D. Charles Thompson, R.Ph., Ph.D., D.A.B.T. Supervisor/Team Leader: Lois M. Freed, Ph.D. Division Director: Russell G. Katz, M.D. Project Manager: Susan B. Daugherty, R.N., B.S.N. Disclaimer Except as specifically identified, all data and information discussed below and necessary for approval of NDA 21-879 are owned by Avanir Pharmaceuticals, Inc. or are data for which Avanir Pharmaceuticals, Inc. has obtained a written right of reference. Any information or
Recommended publications

  • Health Hazard Evaluation Report 1983-0019-1562

    r ILi:. llUr I Health Hazard . Evaluation HETA 83-019-1562 I BERLEX LABS. Report WAYNE., NEW JERSEY . "'-':'. ·· J· PREFACE .......~ The Hazard Evaluation~ ·- ~nd .. "rechni cal Assistance Branch of NIOSH conducts field i nyesti gations of possible hea.lth hazards i n the workplace. These investigations ~are conducted ~under the authority of Section 20(a)(6) of the Occupational Safety and.,Heal'ttr Act of 1970 , 29 u ~ s.c. 66~(a)(6) which authorizes t he Secretary of Health·and Human Services, following a written request from any employer of~ au~horized representative of employees, to determine whether any substance normally found in the place of employ~nt has potentiall~ toxic· .effects in such concentrations as used or fotmd. The Hazard Evaluations and Technical Assistance Branch also provides, upon request, medical, nursing, and industrial hygiene technical and consultative assistance (TA) to Federal, state, and local agencies; labor; industry and other groups or individuals to control occupational health hazards and to prevent related trauma and disease. Mention of company nair.es or products does not constitute e ndorsement by the National Institute for Occupational Safety and Health. HETA 83-019-1562 Investigators: SEPTEMBER, 1985 REVISED Raja Igliewicz, RN, MS BERLEX LABS. Michael Schmidt, MD WAYNE, NEW JERSEY Peter Gann, MD 1. SUMMARY In October, 1982, the National Institute for Occupational Safety and Health (NIOSH) received a request to evaluate workers involved in the production of a drug, quinidine gluconate at Berlex Laborateries, Wayne, N.J. These workers had developed work-related skin rashes and respiratory symptoms. Staff from the Occupational Health Program of the New Jersey State Department of Health performed the investigation under a cooperative agreement with NlOSH.
  • Focus on Over-The-Counter Drugs' Misuse: a Systematic Review On

    Focus on Over-The-Counter Drugs' Misuse: a Systematic Review On

    SYSTEMATIC REVIEW published: 07 May 2021 doi: 10.3389/fpsyt.2021.657397 Focus on Over-the-Counter Drugs’ Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants Fabrizio Schifano 1, Stefania Chiappini 1,2*, Andrea Miuli 2, Alessio Mosca 2, Maria Chiara Santovito 2, John M. Corkery 1, Amira Guirguis 3, Mauro Pettorruso 2, Massimo Di Giannantonio 2 and Giovanni Martinotti 2 1 Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom, 2 Department of Neuroscience, Imaging and Clinical Sciences, “G. D’Annunzio” University, Chieti, Italy, 3 Swansea University Medical School, Institute of Life Sciences 2, Swansea Edited by: University, Swansea, United Kingdom Nicolas Simon, Aix Marseille Université, France Background: Over the past 20 years or so, the drug misuse scenario has seen the Reviewed by: Nicolas Franchitto, emergence of both prescription-only and over-the-counter (OTC) medications being Université Toulouse III Paul reported as ingested for recreational purposes. OTC drugs such as antihistamines, Sabatier, France Oussama Kebir, cough/cold medications, and decongestants are reportedly the most popular in being Institut National de la Santé et de la diverted and misused. Recherche Médicale (INSERM), France Objective: While the current related knowledge is limited, the aim here was to *Correspondence: examine the published clinical data on OTC misuse, focusing on antihistamines Stefania Chiappini (e.g., diphenhydramine, promethazine, chlorpheniramine, and dimenhydrinate), [email protected] dextromethorphan (DXM)- and codeine-based cough medicines, and the nasal Specialty section: decongestant pseudoephedrine. This article was submitted to Methods: A systematic literature review was carried out with the help of Scopus, Addictive Disorders, a section of the journal Web of Science databases, and the related gray literature.
  • Pharmacology/Therapeutics Ii Block 1 Handouts – 2015-16

    Pharmacology/Therapeutics Ii Block 1 Handouts – 2015-16

    PHARMACOLOGY/THERAPEUTICS II BLOCK 1 HANDOUTS – 2015‐16 55. H2 Blockers, PPls – Moorman 56. Palliation of Contipation & Nausea/Vomiting – Kristopaitis 57. On‐Line Only – Principles of Clinical Toxicology – Kennedy 58. Anti‐Parasitic Agents – Johnson Histamine Antagonists and PPIs January 6, 2016 Debra Hoppensteadt Moorman, Ph.D. Histamine Antagonists and PPIs Debra Hoppensteadt Moorman, Ph.D. Office # 64625 Email: [email protected] KEY CONCEPTS AND LEARNING OBJECTIVES . 1 To understand the clinical uses of H2 receptor antagonists. 2 To describe the drug interactions associated with the use of H2 receptor antagonists. 3 To understand the mechanism of action of PPIs 4 To describe the adverse effects and drugs interactions with PPIs 5 To understand when the histamine antagonists and the PPIs are to be used for treatment 6 To describe the drugs used to treat H. pylori infection Drug List: See Summary Table. Histamine Antagonists and PPIs January 6, 2016 Debra Hoppensteadt Moorman, Ph.D. Histamine Antagonists and PPIs I. H2 Receptor Antagonists These drugs reduce gastric acid secretion, and are used to treat peptic ulcer disease and gastric acid hypersecretion. These are remarkably safe drugs, and are now available over the counter. The H2 antagonists are available OTC: 1. Cimetidine (Tagamet®) 2. Famotidine (Pepcid®) 3. Nizatidine (Axid®) 4. Ranitidine (Zantac®) All of these have different structures and, therefore, different side-effects. The H2 antagonists are rapidly and well absorbed after oral administration (bioavailability 50-90%). Peak plasma concentrations are reached in 1-3 hours, and the drugs have a t1/2 of 1-3 hours. H2 antagonists also inhibit stimulated (due to feeding, gastrin, hypoglycemia, vagal) acid secretion and are useful in controlling nocturnal acidity – useful when added to proton pump therapy to control “nocturnal acid breakthrough”.
  • International Emergency Medicine a Guide for Clinicians in Resource-Limited Settings

    International Emergency Medicine a Guide for Clinicians in Resource-Limited Settings

    International Emergency Medicine A Guide for Clinicians in Resource-Limited Settings Joseph Becker, MD and Erika Schroeder, MD, MPH Editors-in-Chief Bhakti Hansoti, MBcHB • Gabrielle Jacquet, MD, MPH Navigating this PDF Handbook of International Emergency Medicine Use left mouse button to advance one page. Use right mouse button to go back one page. Editorial Staff Editors-in-Chief “Home” key on keyboard jumps to cover. “End” key on keyboard jumps to last page. Joseph Becker, MD and Erika Schroeder, MD, MPH Associate Editors Navigate to specific chapters using the table of contents. Bhakti Hansoti, MBcHB and Gabrielle Jacquet, MD, MPH Touch “Escape” to exit full-screen mode. Faculty Editors Kris Arnold, MD S.V. Mahadevan, MD Christine Babcock, MD Ian Martin, MD Elizabeth DeVos, MD Stephanie Kayden, MD, MPH Kate Douglass, MD, MPH Matthew Strehlow, MD Linda Druelinger, MD Christian Theodosis, MD, MPH Troy Foster, MD Susan Thompson, DO Disclaimer Simon Kotlyar, MD, MSc David Walker, MD This handbook is intended as a general guide only. While the editors have taken Suzanne Lippert, MD, MS reasonable measures to ensure the accuracy of drug and dosing information used in this guide, the user is encouraged to consult other resources or consultants Authors when necessary to confirm appropriate therapy, side effects, interactions, and Spencer Adoff, MD Mark Goodman, MD contraindications. The publisher, authors, editors, and sponsoring organizations James Ahn, MD Jessica Holly, MD specifically disclaim any liability for any omissions or errors found in this handbook, Lauren Alexander, MD Aaron Hultgren, MD, MPH for appropriate use, or treatment errors. Furthermore, although this handbook is as Maya Arii, MD, MPH Aliasgher Hussain, MD comprehensive as possible, the vast differences in emergency practice settings may Nanaefua Baidoo, MD Masayuki Iyanaga, MD necessitate treatment approaches other than presented here.
  • (12) United States Patent (10) Patent No.: US 6,844,355 B2 Somberg Et Al

    (12) United States Patent (10) Patent No.: US 6,844,355 B2 Somberg Et Al

    USOO684.4355B2 (12) United States Patent (10) Patent No.: US 6,844,355 B2 Somberg et al. (45) Date of Patent: Jan. 18, 2005 (54) OPTICALLY ACTIVE ISOMERS OF QUININE Catterall, (1992) Physiol. Rev. 72(supp):S15-S48. AND QUINDINE AND THEIR RESPECTIVE Chan et al., (1991) J. Chromatogr. 571:291-297. BIOLOGICALACTION Chen et al., (1998) Nature 392:293–296. (75) Inventors: John C. Somberg, Lake Forest, IL Coplen et al., (1991) Circulation 84:527. (US); Vasant Ranade, Libertyville, IL Drabowicz et al., (1984) “Chemical Abstracts” Phosphorus (US) Sulfur 16:2676–270 (XP002165239). Engler et al., (1985) Helv. Chim. Acta. 68:789–800. (73) Assignee: Academic Pharmaceuticals, Inc., Lake Ficker et al., (1998) Circ. Res. 82:386–395. Bluff, IL (US) Gellens et al., (1992) Proc. Natl. Acad. Sci. 89:554–558. (*) Notice: Subject to any disclaimer, the term of this Gutzwiller et al., (1973) “Chemical Abstracts” Helv. Chim. patent is extended or adjusted under 35 Acta. 79:1494–1503 (XP002165238). U.S.C. 154(b) by 0 days. Hartmann et al. (1994) Circ. Res. 75:114-122. Karle I.L. et al., (1981) Proc. Natl. Acad. Sci. 78:5938–5941. (21) Appl. No.: 10/168,919 Karle, J.M. (1997) Antimicrob. Agents Chemother. (22) PCT Filed: Dec. 22, 2000 41:791-794. Kiehn et al. (1996) Circulation 94:2572–2579. (86) PCT No.: PCT/US00/352.13 Krafte et al., (1994) Europ. J. Pharma. 266:245-254. S371 (c)(1), Li et al. (1996) Circ. Res. 78:689-696. (2), (4) Date: Oct. 30, 2002 Sanguinetti et al., (1990) J.
  • Recreational Use of Popular Otc Drugs – Pharmacological Review

    Recreational Use of Popular Otc Drugs – Pharmacological Review

    FARMACIA, 2018, Vol. 66, 2 REVIEW RECREATIONAL USE OF POPULAR OTC DRUGS – PHARMACOLOGICAL REVIEW PIOTR JAKUBOWSKI *, PUCHAŁA ŁUKASZ, GRZEGORZEWSKI WALDEMAR Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Warmia and Mazury in Olsztyn, Aleja Warszawska 30, 11-041 Olsztyn, Poland *corresponding author: [email protected] Manuscript received: June 2017 Abstract Over-the-counter medicines use disorder is a serious and growing health problem affecting mainly adolescents. Drugs from many therapeutic classes, including antitussive agents such as dextromethorphan and codeine, antihistamine drugs diphenhydramine and dimenhydrinate, nasal decongestant pseudoephedrine and anti-inflammatory drug benzydamine are used for this purpose. Habitual users of most of these drugs can develop symptoms of substance dependence. When used in large quantities, these drugs can cause numerous toxic effects, including death. Recently many countries introduced legal restrictions in codeine, dextromethorphan and pseudoephedrine sales. Rezumat Abuzul de medicamente eliberate fără rețetă reprezintă o problemă gravă a sănătății care afectează în principal adolescenții. În acest scop, sunt utilizate medicamente din mai multe clase terapeutice, incluzând agenți antitusivi precum dextrometorfan și codeină, medicamente antihistaminice difenhidramină și dimenhidrinat, pseudoefedrină decongestionant nazal și benzidamină medicament antiinflamator. Utilizatorii obișnuiți ai majorității acestor medicamente pot dezvolta simptome de
  • Application of Neutron Activation Analysis Method on Biomonitors for Assessing Environment Quality

    Application of Neutron Activation Analysis Method on Biomonitors for Assessing Environment Quality

    NUCLEAR – 2016 ███████████████████████████████████████████████████████████████████████████████████████████████████████████████████████████████████████████████████████████████████ █████████████████████████████████████████████████ APPLICATION OF NEUTRON ACTIVATION ANALYSIS METHOD ON BIOMONITORS FOR ASSESSING ENVIRONMENT QUALITY E.A. NITESCU, S. VALECA, A.F. BUCSA* University of Pitesti, Pitesti, Romania, [email protected] *RATEN-ICN Pitesti, Mioveni, Romania, [email protected] ABSTRACT The purpose of this paper is to determine the chemical elements concentrations which affect both the population health and environment, such as toxic agents which are contained in air and are retained by precipitation inside the biomonitors vegetal tissues. The Neutron Activation Analysis is an analytic technique based on measuring the numbers and the energy of gamma radiation emitted by the radioactive isotopes produced in the sample matrix by irradiation with thermal neutrons in a nuclear reactor [1]. Usually, the samples are irradiated together with specific neutron flux monitors, duplicates and interest elements standards for a prior selected period of time inside the core of nuclear reactor. After the irradiation experiment and the specific radioactive decaying, can proceed measuring the gamma energies spectrum by using a high resolution detection system (HPGe – High Purity Germanium crystal) for gamma spectrometry and then assess the impact of the traced elements on population and environment. Key words: Neutron Activation Analysis,
  • Dietary Supplements Compendium Volume 1

    Dietary Supplements Compendium Volume 1

    2015 Dietary Supplements Compendium DSC Volume 1 General Notices and Requirements USP–NF General Chapters USP–NF Dietary Supplement Monographs USP–NF Excipient Monographs FCC General Provisions FCC Monographs FCC Identity Standards FCC Appendices Reagents, Indicators, and Solutions Reference Tables DSC217M_DSCVol1_Title_2015-01_V3.indd 1 2/2/15 12:18 PM 2 Notice and Warning Concerning U.S. Patent or Trademark Rights The inclusion in the USP Dietary Supplements Compendium of a monograph on any dietary supplement in respect to which patent or trademark rights may exist shall not be deemed, and is not intended as, a grant of, or authority to exercise, any right or privilege protected by such patent or trademark. All such rights and privileges are vested in the patent or trademark owner, and no other person may exercise the same without express permission, authority, or license secured from such patent or trademark owner. Concerning Use of the USP Dietary Supplements Compendium Attention is called to the fact that USP Dietary Supplements Compendium text is fully copyrighted. Authors and others wishing to use portions of the text should request permission to do so from the Legal Department of the United States Pharmacopeial Convention. Copyright © 2015 The United States Pharmacopeial Convention ISBN: 978-1-936424-41-2 12601 Twinbrook Parkway, Rockville, MD 20852 All rights reserved. DSC Contents iii Contents USP Dietary Supplements Compendium Volume 1 Volume 2 Members . v. Preface . v Mission and Preface . 1 Dietary Supplements Admission Evaluations . 1. General Notices and Requirements . 9 USP Dietary Supplement Verification Program . .205 USP–NF General Chapters . 25 Dietary Supplements Regulatory USP–NF Dietary Supplement Monographs .
  • Small Dose... Big Poison

    Small Dose... Big Poison

    Traps for the unwary George Braitberg Ed Oakley Small dose... Big poison All substances are poisons; Background There is none which is not a poison. It is not possible to identify all toxic substances in a single The right dose differentiates a poison from a remedy. journal article. However, there are some exposures that in Paracelsus (1493–1541)1 small doses are potentially fatal. Many of these exposures are particularly toxic to children. Using data from poison control centres, it is possible to recognise this group of Poisoning is a frequent occurrence with a low fatality rate. exposures. In 2008, almost 2.5 million human exposures were reported to the National Poison Data System (NPDS) in the United Objective States, of which only 1315 were thought to contribute This article provides information to assist the general to fatality.2 The most common poisons associated with practitioner to identify potential toxic substance exposures in children. fatalities are shown in Figure 1. Polypharmacy (the ingestion of more than one drug) is far more common. Discussion In this article the authors report the signs and symptoms Substances most frequently involved in human exposure are shown of toxic exposures and identify the time of onset. Where in Figure 2. In paediatric exposures there is an over-representation clear recommendations on the period of observation and of personal care products, cleaning solutions and other household known fatal dose are available, these are provided. We do not discuss management or disposition, and advise readers products, with ingestions peaking in the toddler age group. This to contact the Poison Information Service or a toxicologist reflects the acquisition of developmental milestones and subsequent for this advice.
  • Drome De ROSENTHAL (II) 14944 Rc)SSLE's Syndrome

    Drome De ROSENTHAL (II) 14944 Rc)SSLE's Syndrome

    ROSSLE'S 14944-14967 Saccharomyces halluzinatorisches Angst-Syndrom) / syn­ 14954 rules, pregnancy control / Schwanger­ drome de ROSENTHAL (II) schaftskontrollregeln f (1. moglichst nicht 14944 Rc)SSLE'S syndrome / ROSSLE' Syndrom (Se­ invasiv [Ultraschall], 2. nur mit kurzlebigen xogener Kleinwuchs) / nanisme sexoge­ Radionukliden, vor allem zur Diagnose der nique Nieren- und Plazentafunktion, erst ab 3. 14945 rotation, chromosomal / Rotation, chromo­ Trimenon [JANISCH]) / regles de controle de somale f (in Bivalenten mit Chiasma zwi­ grossesse f schen Diplotan und Diakinese eintretende 14955 rules, sense for / Gefuhl fur Regeln n Formverandrung) / rotation chromosomi­ (psych.) / regles, sens pour m quef 14956 ruling forecast; science forecasting / Richtli­ 14946 round pronator syndrome / Pronator-teres­ nienprognose; Wissenschaftsprognose f / Syndrom (Schwache in den langen Finger­ prevision directrice; prevision scientifique f beugem) / syndrome de pronateur rond 14957 rumors / Geriichte n (konnen aus Traumen 14947 ROVIRALTA'S syndrome / ROVIRALTA' Syn­ entstehen) / rumeurs f drom (Pylorusstenose und Hiatushemie 14958 running, dancing / Laufen, tanzerisches n mit Magenektopie beim Saugling) / syn­ (tagliches ohne Leistungsdruck bis zur Er­ drome phrenopylorique (ROVIRALTA) miidung, besser als Radfahren, Schwim­ 14948 ROWLEY'S syndrome / ROWLEY' Syndrom men, Reiten, halt aerobe Kapazitat kon­ (SchwerhOrigkeit mit Halsfisteln) / syn­ stant, eroffnet Kollateralen und vermehrt drome de ROWLEY Zahl und GroBe der Mitochondrien) / cou­ 14949 ROWLEy-ROSENBERG syndrome / ROWLEY­ rir dansant m ROSENBERG' Syndrom (Gestorte Riickab­ 14959 rupture of the bladder / Blaseruptur f(klin. sorption fast aller Aminosauren) / syn­ Leitsymptom: blutige Dysurie; sichre Dia­ drome de ROWLEy-ROSENBERG gnose: Zystographie mit Kontrastmittel, 14950 rubb~~g, emotional/ Reibung, emotionale f wenn nicht moglich, Probelaparotomie und (bei UbervOlkrung groBres Problem als bei jeder gesicherten Ruptur sofortige Op.
  • Date: 1/9/2017 Question: Botulism Is an Uncommon Disorder Caused By

    Date: 1/9/2017 Question: Botulism Is an Uncommon Disorder Caused By

    6728 Old McLean Village Drive, McLean, VA 22101 Tel: 571.488.6000 Fax: 703.556.8729 www.clintox.org Date: 1/9/2017 Question: Botulism is an uncommon disorder caused by toxins produced by Clostridium botulinum. Seven subtypes of botulinum toxin exist (subtypes A, B, C, D, E, F and G). Which subtypes have been noted to cause human disease and which ones have been reported to cause infant botulism specifically in the United States? Answer: According to the cited reference “Only subtypes A, B, E and F cause disease in humans, and almost all cases of infant botulism in the United States are caused by subtypes A and B. Botulinum-like toxins E and F are produced by Clostridium baratii and Clostridium butyricum and are only rarely implicated in infant botulism” (Rosow RK and Strober JB. Infant botulism: Review and clinical update. 2015 Pediatr Neurol 52: 487-492) Date: 1/10/2017 Question: A variety of clinical forms of botulism have been recognized. These include wound botulism, food borne botulism, and infant botulism. What is the most common form of botulism reported in the United States? Answer: According to the cited reference, “In the United States, infant botulism is by far the most common form [of botulism], constituting approximately 65% of reported botulism cases per year. Outside the United States, infant botulism is less common.” (Rosow RK and Strober JB. Infant botulism: Review and clinical update. 2015 Pediatr Neurol 52: 487-492) Date: 1/11/2017 Question: Which foodborne pathogen accounts for approximately 20 percent of bacterial meningitis in individuals older than 60 years of age and has been associated with unpasteurized milk and soft cheese ingestion? Answer: According to the cited reference, “Listeria monocytogenes, a gram-positive rod, is a foodborne pathogen with a tropism for the central nervous system.
  • 021879Orig1s000

    021879Orig1s000

    CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 021879Orig1s000 OTHER REVIEW(S) 505(b)(2) ASSESSMENT Application Information NDA # 021879 NDA Supplement #: S- N/A Efficacy Supplement Type SE- N/A Proprietary Name: Nuedexta Established/Proper Name: (dextromethorphan/quinidine) Dosage Form: Capsules Strengths: dextromethorphan 20mg with quinidine 10 mg Applicant: Avanir Pharmaceuticals, Inc. Date of Receipt: April 30, 2010 PDUFA Goal Date: October 30, 2010 Action Goal Date (if different): Proposed Indication(s): indicated for the treatment of pseudobulbar affect (PBA) secondary to either amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS) GENERAL INFORMATION 1) Is this application for a recombinant or biologically-derived product and/or protein or peptide product OR is the applicant relying on a recombinant or biologically-derived product and/or protein or peptide product to support approval of the proposed product? YES NO If “YES “contact the (b)(2) review staff in the Immediate Office, Office of New Drugs. ReferenceVersion ID: 2857112 March 2009 page 1 INFORMATION PROVIDED VIA RELIANCE (LISTED DRUG OR LITERATURE) 2) List the information essential to the approval of the proposed drug that is provided by reliance on our previous finding of safety and efficacy for a listed drug or by reliance on published literature. (If not clearly identified by the applicant, this information can usually be derived from annotated labeling.) Source of information* (e.g., Information provided (e.g., published literature, name of pharmacokinetic data, or specific referenced product) sections of labeling) quinidine sulfate nonclinical safety literature nonclinical safety *each source of information should be listed on separate rows 3) Reliance on information regarding another product (whether a previously approved product or from published literature) must be scientifically appropriate.