DOCSLIB.ORG

A Randomized, Double-Blind, Placebo-Controlled Study

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

medRxiv preprint doi: https://doi.org/10.1101/2020.04.06.20055715; this version posted April 11, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 1 Mo%on Sifnos: A randomized, double-blind, placebo-controlled study demonstra%ng the effec%veness of tradipitant in the treatment of mo%on sickness Vasilios M. Polymeropoulos*1, Mark É. Czeisler1#a, Mary M. Gibson1¶, Aus%n A. Anderson1¶, Jane Miglo1#b, Jingyuan Wang1, Changfu Xiao1, Christos M. Polymeropoulos1, Gunther Birznieks1, Mihael H. Polymeropoulos1 1 Vanda Pharmaceu%cals, Washington, District of Columbia, United States of America #a The Ins%tute for Breathing and Sleeping, Aus%n Health, Heidelberg, Victoria, Australia #b College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, United States of America *Corresponding author Email: [email protected] (VMP) ¶These authors contributed equally to this work. NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2020.04.06.20055715; this version posted April 11, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 2 Abstract Background Novel therapies are needed for the treatment of mo%on sickness given the inadequate relief, and bothersome and dangerous adverse effects of currently approved therapies. Neurokinin-1 (NK1) receptor antagonists have the poten%al to be effec%ve in improving the symptoms of mo%on sickness, given the involvement of Substance P in nauseogenic and eme%c pathways and the expression of NK1 receptors in the gastrointes%nal system. Here, we evaluated the efficacy of tradipitant, a novel NK1 receptor antagonist, in preven%ng mo%on sickness in variable sea condi%ons. Methods A total of 126 adults par%cipated in the Mo%on Sifnos Study. Groups of par%cipants were assigned to one of seven boat trips las%ng approximately four hours on the Pacific Ocean. Par%cipants were randomized 1:1 to tradipitant 170 mg or placebo and completed the Mo%on Sickness Severity Scale (MSSS) every 30 minutes, in addi%on to other assessments. Severity of mo%on sickness was assessed with the incidence of vomi%ng and the MSSS. Results Par%cipants on tradipitant had a significantly lower incidence of vomi%ng as compared to those on placebo across all boat trips (tradipitant=17.5%, placebo=39.7%, p=0.0039). For trips exposed to rough sea condi%ons, the difference in the incidence of vomi%ng between the groups was more drama%c (tradipitant=15.79%, placebo=72.22%, p=0.0009). Across these trips, mo%on sickness symptoms were significantly lower in the tradipitant group compared to the placebo group (tradipitant=3.19, placebo=4.57, p=0.0235). Discussion medRxiv preprint doi: https://doi.org/10.1101/2020.04.06.20055715; this version posted April 11, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 3 Tradipitant has the poten%al to be an effec%ve therapy for the preven%on of vomi%ng and treatment of nausea in people with mo%on sickness. medRxiv preprint doi: https://doi.org/10.1101/2020.04.06.20055715; this version posted April 11, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 4 Introduc8on Mo%on sickness is a disorder that has been plaguing travelers in various vehicles since an%quity [1]. Nausea and vomi%ng are the core symptoms of mo%on sickness [2]. Other symptoms may include swea%ng, dizziness, headache, irritability, and loss of appe%te. The e%ology and pathogenesis of disease are most commonly theorized as an aggrega%on of conflic%ng sensory informa%on that leads to an unpleasant physiological reac%on resul%ng in the symptoms described above [3-4]. Travelers with mo%on sickness have impaired cogni%ve performance [5], which can be of increased burden and danger in professional environments. Although there is a significant demand for efficacious therapies, the only currently approved treatments in the United States are dimenhydrinate (Dramamine), hyoscine (Scopolamine), and meclizine (Dramamine non-drowsy). These therapies carry incomplete efficacy and can have bothersome and dangerous adverse effects, such as drowsiness and dizziness [6]. An ideal therapy would be efficacious in the treatment of the cardinal symptoms of nausea and vomi%ng without inducing the array of adverse effects as seen with current medica%ons. NK1 receptor antagonists have the poten%al to be effec%ve in the treatment of mo%on sickness in humans. NK1 receptors are expressed in the network of brainstem nuclei including the area postrema and nucleus tractus solitarius (NTS) that are involved in the regula%on of vomi%ng [7]. Transmission of emetogenic sensory and emo%onal signals from higher cor%cal centers to the NTS can result in reflexive vomi%ng. The ves%bular centers in the brainstem send signals to the NTS to trigger emesis in response to ver%go, dizziness, or visuospa%al disorienta%on [8]. When the NTS receives the direct input from those sources, Substance P (SP), the most abundant neurokinin, is released [9]. Substance P preferen%ally binds to the NK1 receptors densely located in the NTS, which triggers this cascade of physiological responses, including emesis [8]. NK1 receptor antagonists are effec%ve and approved for the treatment of nausea and vomi%ng in other indica%ons. Maropitant is an approved NK1 receptor antagonist shown to be effec%ve for the preven%on of vomi%ng in dogs and cats due to mo%on sickness [10]. The NK1 receptor antagonist aprepitant is approved for the preven%on of post-opera%ve nausea and vomi%ng [11]. medRxiv preprint doi: https://doi.org/10.1101/2020.04.06.20055715; this version posted April 11, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 5 Tradipitant (VLY-686) is a novel NK1 receptor antagonist in development for the treatment of gastroparesis and atopic derma%%s. Tradipitant was shown to be effec%ve in the treatment of nausea and vomi%ng in gastroparesis in a 4-week randomized study [12]. Given this evidence to support the use of tradipitant as an NK1 receptor antagonist to treat nausea and vomi%ng and specifically in mo%on sickness, we designed and conducted the Mo%on Sifnos Study. Regarding the elec%on of modality to induce mo%on sickness, we conducted the study in natural sea condi%ons in the Pacific Ocean for several reasons: (1) seasickness is the classical archetype to induce mo%on sickness (2) exposure to natural sea mo%on supports the study condi%ons as ecologically valid, and (3) simula%on in real-world condi%ons offers the unique opportunity to evaluate the medica%on as it would be used once available to the public. Further, sea travel consists of ver%cal sinusoidal mo%ons induced by waves. The amplitude of these mo%ons is related to the wave height and corresponds to heave (linear ver%cal mo%on), which is the strongest s%mulus to induce mo%on sickness, contribu%ng more to provoca%on than the angular accelera%ons of pitch, roll, and yaw [13]. The frequency and accelera%on of ver%cal sinusoidal mo%ons can also be assessed. In an evalua%on of mo%on sickness incidence as a func%on of the frequency and accelera%on of ver%cal sinusoidal mo%on, wave frequencies around 0.2 Hz were most provoca%ve, and mo%on sickness incidence increased with accelera%on (propor%onal to the amplitude of the waves) across all wave frequencies [14]. The goal of the Mo%on Sifnos Study was to examine the effects of tradipitant in trea%ng the symptoms of mo%on sickness, with a focus on the core symptoms. medRxiv preprint doi: https://doi.org/10.1101/2020.04.06.20055715; this version posted April 11, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 6 Materials and methods The Mo%on Sifnos Study (NCT03772340) was a randomized, double-blind placebo-controlled study on the Pacific Ocean near Los Angeles, California to evaluate the efficacy and safety of tradipitant in the treatment of mo%on sickness. Par8cipants Eligible par%cipants were adults aged between 18 and 75 years with a history of mo%on sickness, otherwise in good health (determined by medical and psychiatric history, physical examina%on, electrocardiography, serum chemistry, hematology, urinalysis, and urine toxicology) and lacking any major nausea-inducing disorders.
Recommended publications
  • Adverse Drug Reactions Sample Chapter

    Adverse Drug Reactions Sample Chapter

    Sample copyright Pharmaceutical Press www.pharmpress.com 5 Drug-induced skin reactions Anne Lee and John Thomson Introduction Cutaneous drug eruptions are one of the most common types of adverse reaction to drug therapy, with an overall incidence rate of 2–3% in hos- pitalised patients.1–3 Almost any medicine can induce skin reactions, and certain drug classes, such as non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics and antiepileptics, have drug eruption rates approaching 1–5%.4 Although most drug-related skin eruptions are not serious, some are severe and potentially life-threatening. Serious reac- tions include angio-oedema, erythroderma, Stevens–Johnson syndrome and toxic epidermal necrolysis. Drug eruptions can also occur as part of a spectrum of multiorgan involvement, for example in drug-induced sys- temic lupus erythematosus (see Chapter 11). As with other types of drug reaction, the pathogenesis of these eruptions may be either immunological or non-immunological. Healthcare professionals should carefully evalu- ate all drug-associated rashes. It is important that skin reactions are identified and documented in the patient record so that their recurrence can be avoided. This chapter describes common, serious and distinctive cutaneous reactions (excluding contact dermatitis, which may be due to any external irritant, including drugs and excipients), with guidance on diagnosis and management. A cutaneous drug reaction should be suspected in any patient who develops a rash during a course of drug therapy. The reaction may be due to any medicine the patient is currently taking or has recently been exposed to, including prescribed and over-the-counter medicines, herbal or homoeopathic preparations, vaccines or contrast media.
  • Chapter 5 Biological Effects of Ionizing Radiation Page I

    Chapter 5 Biological Effects of Ionizing Radiation Page I

    CHAPTER 5 BIOLOGICAL EFFECTS OF IONIZING RADIATION PAGE I. Introduction ............................................................................................................................ 5-3 II. Mechanisms of Radiation Damage ........................................................................................ 5-3 A. Direct Action .............................................................................................................. 5-3 B. Indirect Action ........................................................................................................... 5-3 III. Determinants of Biological Effects ........................................................................................ 5-4 A. Rate of Absorption ..................................................................................................... 5-5 B. Area Exposed ............................................................................................................. 5-5 C. Variation in Species and Individual Sensitivity ......................................................... 5-5 D. Variation in Cell Sensitivity ....................................................................................... 5-5 IV. The Dose-Response Curve ..................................................................................................... 5-6 V. Pattern of Biological Effects .................................................................................................. 5-7 A. Prodromal Stage ........................................................................................................
  • Acute Radiation Syndrome (ARS) – Treatment of the Reduced Host Defense

    Acute Radiation Syndrome (ARS) – Treatment of the Reduced Host Defense

    International Journal of General Medicine Dovepress open access to scientific and medical research Open Access Full Text Article REVIEW Acute radiation syndrome (ARS) – treatment of the reduced host defense Lars Heslet1 Background: The current radiation threat from the Fukushima power plant accident has prompted Christiane Bay2 rethinking of the contingency plan for prophylaxis and treatment of the acute radiation syndrome Steen Nepper-Christensen3 (ARS). The well-documented effect of the growth factors (granulocyte colony-stimulating factor [G-CSF] and granulocyte-macrophage colony-stimulating factor [GM-CSF]) in acute radia- 1Serendex ApS, Gentofte; 2University of Copenhagen, tion injury has become standard treatment for ARS in the United States, based on the fact that Medical Faculty, Copenhagen; growth factors increase number and functions of both macrophages and granulocytes. 3 Department of Head and Neck Review of the current literature. Surgery, Otorhinolaryngology, Methods: Køge University Hospital, Køge, Results: The lungs have their own host defense system, based on alveolar macrophages. After Denmark radiation exposure to the lungs, resting macrophages can no longer be transformed, not even during systemic administration of growth factors because G-CSF/GM-CSF does not penetrate the alveoli. Under normal circumstances, locally-produced GM-CSF receptors transform resting macrophages into fully immunocompetent dendritic cells in the sealed-off pulmonary compartment. However, GM-CSF is not expressed in radiation injured tissue due to deferves- cence of the macrophages. In order to maintain the macrophage’s important role in host defense after radiation exposure, it is hypothesized that it is necessary to administer the drug exogenously in order to uphold the barrier against exogenous and endogenous infections and possibly prevent the potentially lethal systemic infection, which is the main cause of death in ARS.
  • Angioedema After Long-Term Use of an Angiotensin-Converting Enzyme Inhibitor

    Angioedema After Long-Term Use of an Angiotensin-Converting Enzyme Inhibitor

    J Am Board Fam Pract: first published as 10.3122/jabfm.10.5.370 on 1 September 1997. Downloaded from BRIEF REPORTS Angioedema After Long-Term Use of an Angiotensin-Converting Enzyme Inhibitor Adriana]. Pavietic, MD Angioedema is an uncommon adverse effect of cyclobenzaprine, her angioedema was initially be­ angiotensin-converting enzyme (ACE) inhib­ lieved to be an allergic reaction to this drug, and itors. Its frequency ranges from 0.1 percent in pa­ it was discontinued. She was also given 125 mg of tients on captopril, lisinopril, and quinapril to 0.5 methylprednisolone intramuscularly. Her an­ percent in patients on benazepril. l Most cases are gioedema did not improve, and she returned to mild and occur within the first week of treat­ the clinic the following day. She was seen by an­ ment. 2-4 Recent reports indicate that late-onset other physician, who discontinued lisinopril, and angioedema might be more prevalent than ini­ her symptoms resolved within 24 hours. Mter her tially thought, and fatal cases have been de­ ACE inhibitor was discontinued, she experienced scribed.5-11 Many physicians are not familiar with more symptoms and an increased frequency of late-onset angioedema associated with ACE in­ palpitations, but she had no change in exercise hibitors, and a delayed diagnosis can have poten­ tolerance. A cardiologist was consulted, who pre­ tially serious consequences.5,8-II scribed the angiotensin II receptor antagonist losartan (initially at dosages of 25 mg/d and then Case Report 50 mg/d). The patient was advised to report any A 57-year-old African-American woman with symptoms or signs of angioedema immediately copyright.
  • Angioedema, a Life-Threatening Adverse Reaction to ACE-Inhibitors

    Angioedema, a Life-Threatening Adverse Reaction to ACE-Inhibitors

    DOI: 10.2478/rjr-2019-0023 Romanian Journal of Rhinology, Volume 9, No. 36, October - December 2019 LITERATURE REVIEW Angioedema, a life-threatening adverse reaction to ACE-inhibitors Ramona Ungureanu1, Elena Madalan2 1ENT Department, “Dr. Victor Babes” Diagnostic and Treatment Center, Bucharest, Romania 2Allergology Department, “Dr. Victor Babes” Diagnostic and Treatment Center, Romania ABSTRACT Angioedema with life-threatening site is one of the most impressive and serious reasons for presenting to the ENT doctor. Among different causes (tumors, local infections, allergy reactions), an important cause is the side-effect of the angiotensin converting enzyme (ACE) inhibitors drugs. ACE-inhibitors-induced angioedema is described to be the most frequent form of bradykinin- mediated angioedema presented in emergency and also one of the most encountered drug-induced angioedema. The edema can involve one or more areas of the head and neck region, the most affected being the face, the lips, the tongue, followed by the larynx, when it may determine respiratory distress and even death. There are no specific diagnosis tests available and the positive diagnosis of ACE-inhibitors-induced angioedema is an exclusion diagnosis. The authors performed a review of the most important characteristics of the angioedema caused by ACE-inhibitors and present their experience emphasizing the diagnostic algorithm. KEYWORDS: angioedema, ACE-inhibitors, hereditary angioedema, bradykinin, histamine. INTRODUCTION with secondary local extravasation of plasma and tissue swelling5,6. Angioedema (AE) is a life-threatening condition Based on this pathomechanism, the classification presented as an asymmetric, localised, well-demar- of angioedema comprises three major types: 1). cated swelling1, located in the mucosal and submu- bradykinin-mediated – with either complement C1 cosal layers of the upper respiratory airways.
  • Pilot Study to Assess Outcomes of a Drug Allergy Clarification Service on a General Medicine Floor at a Local Community Hospital Crystal M

    Pilot Study to Assess Outcomes of a Drug Allergy Clarification Service on a General Medicine Floor at a Local Community Hospital Crystal M

    Original Research PRACTICE-BASED RESEARCH Pilot Study to Assess Outcomes of a Drug Allergy Clarification Service on a General Medicine Floor at a Local Community Hospital Crystal M. Deas, PharmD, BCPS1; C. Whitney White, PharmD, BCPS2 1Samford University, McWhorter School of Pharmacy, Clinical Pharmacist, Cooper Green Mercy Health Services, Birmingham, AL 2University of Mississippi School of Pharmacy, University of Mississippi Medical Center, Jackson, MS Abstract Purpose: Drug allergy documentation in the patient medical record varies in level of detail, and drug intolerances are often inappropriately documented as an allergy in the medical record. A pilot study was conducted to determine the impact of a pharmacy- led drug allergy clarification service. Methods: The pilot quality improvement service was implemented in Fall 2016. General medicine patients were identified through daily census reporting and the electronic medical record (EMR) was reviewed within 72 hours of admission for documented drug allergies and/or intolerances. Patients were interviewed by a clinical pharmacist or a fourth year pharmacy student to determine a complete drug allergy and intolerance history. Results: A total of 55 patients were interviewed and received the pilot service. A drug allergy/intolerance was documented in EMR for 54.5% (n=30) of patients interviewed. Of those 30 patients, 96.6% (n=29) were noted to have at least one discrepancy between EMR documentation and patient interview. The primary discrepancy noted was drug allergies or intolerances documented in the EMR without a description of the reaction. Conclusion: A pharmacy-led drug allergy clarification service was effective in identifying and clarifying EMR documentation of patients’ drug allergies and intolerances.
  • NIH Public Access Author Manuscript Neurocrit Care

    NIH Public Access Author Manuscript Neurocrit Care

    NIH Public Access Author Manuscript Neurocrit Care. Author manuscript; available in PMC 2013 June 10. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Neurocrit Care. 2012 December ; 17(3): 441–467. doi:10.1007/s12028-012-9747-4. Brain Resuscitation in the Drowning Victim Alexis A. Topjian, The Children’s Hospital of Philadelphia, 7th floor, 34th Street and Civic Center Boulevard, Suite 7C23, Philadelphia, PA 19104, USA, [email protected] Robert A. Berg, The Children’s Hospital of Philadelphia, 7th floor, 34th Street and Civic Center Boulevard, Suite 7C23, Philadelphia, PA 19104, USA, [email protected] Joost J. L. M. Bierens, Maatschappij tot Redding van Drenkelingen, Amsterdam, The Netherlands, [email protected] Christine M. Branche, National Institute for Occupational Safety and Health/Centers for Disease Control, Washington, DC, USA, [email protected] Robert S. Clark, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, USA, [email protected] Hans Friberg, Department of Intensive and Perioperative Care, Skåne University Hospital, Lund, Sweden, [email protected]; Department of Clinical Sciences, Lund University, 221 85 Lund, Sweden Cornelia W. E. Hoedemaekers, Department of ICU, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands, [email protected] Michael Holzer, Department of Emergency Medicine, Medical University of Vienna, Waehringer Guertel 18-20/6D, 1090 Vienna, Austria, [email protected] Laurence M. Katz, Department of Emergency Medicine, Neurosciences, University of North Carolina at Chapel Hill, 101 Manning Drive, Chapel Hill, NC 27599, USA, [email protected] Johannes T.
  • About Drug Side-Effects and Allergies

    About Drug Side-Effects and Allergies

    About drug side-effects and allergies Introduction This leaflet has been produced to provide you with information about side-effects of medicines and drug allergies, and the differences between the two. There are a variety of ways in which people can experience adverse reactions to medications, whether prescribed or bought 'over-the-counter'. Most of these effects are not an 'allergy'. Contrary to what most people think, only small amounts (5-10%) of all adverse drug reactions are caused by a drug allergy. It is important to tell the doctor or healthcare professional looking after you about any drug allergies or side-effects to drugs you may have/or had as this may affect your current treatment. It is important to know the difference between a drug allergy and side-effect because saying you have a drug allergy when in fact it is a side-effect may unnecessarily restrict the treatment choices available to treat your condition. What should I be aware of when taking my medicines? Many medicines can cause side-effects e.g. some medicines may affect your sight or co-ordination or make you sleepy, which may affect your ability to drive, perform skilled tasks safely. The information leaflet provided with your medicine will list any side effects which are known to be linked to your medicine. All medications have side-effects because of the way they work. The majority of people get none, or very few, but some people are more prone to them. The most common side-effects are usually nausea, vomiting, diarrhoea (or occasionally constipation), tiredness, rashes, itching, headaches and blurred vision.
  • Neurokinin Receptor NK Receptor

    Neurokinin Receptor NK Receptor

    Neurokinin Receptor NK receptor There are three main classes of neurokinin receptors: NK1R (the substance P preferring receptor), NK2R, and NK3R. These tachykinin receptors belong to the class I (rhodopsin-like) G-protein coupled receptor (GPCR) family. The various tachykinins have different binding affinities to the neurokinin receptors: NK1R, NK2R, and NK3R. These neurokinin receptors are in the superfamily of transmembrane G-protein coupled receptors (GPCR) and contain seven transmembrane loops. Neurokinin-1 receptor interacts with the Gαq-protein and induces activation of phospholipase C followed by production of inositol triphosphate (IP3) leading to elevation of intracellular calcium as a second messenger. Further, cyclic AMP (cAMP) is stimulated by NK1R coupled to the Gαs-protein. The neurokinin receptors are expressed on many cell types and tissues. www.MedChemExpress.com 1 Neurokinin Receptor Antagonists, Agonists, Inhibitors, Modulators & Activators Aprepitant Befetupitant (MK-0869; MK-869; L-754030) Cat. No.: HY-10052 (Ro67-5930) Cat. No.: HY-19670 Aprepitant (MK-0869) is a selective and Befetupitant is a high-affinity, nonpeptide, high-affinity neurokinin 1 receptor antagonist competitive tachykinin 1 receptor (NK1R) with a Kd of 86 pM. antagonist. Purity: 99.67% Purity: >98% Clinical Data: Launched Clinical Data: No Development Reported Size: 10 mM × 1 mL, 5 mg, 10 mg, 50 mg, 100 mg, 200 mg Size: 1 mg, 5 mg Biotin-Substance P Casopitant mesylate Cat. No.: HY-P2546 (GW679769B) Cat. No.: HY-14405A Biotin-Substance P is the biotin tagged Substance Casopitant mesylate (GW679769B) is a potent, P. Substance P (Neurokinin P) is a neuropeptide, selective, brain permeable and orally active acting as a neurotransmitter and as a neurokinin 1 (NK1) receptor antagonist.
  • Adverse Drug Reaction Reporting

    Adverse Drug Reaction Reporting

    P T Chapter 40 Adverse Drug Reaction Reporting Lee B. Murdaugh, RPh, PhD The Conditions of Participation standards of the Centers for Medicare & Medicaid Services (CMS) and the standards of accrediting organizations such as The Joint Commission, the Healthcare Facilities Accredi- tation Program (HFAP), and the National Integrated Accreditation for Healthcare Organizations (NIAHOSM) require hospitals to identify and report adverse drug reactions (ADRs). These ADRs must be reported to LEARNING OBJECTIVES patients’ attending physicians and the hospital’s quality assessment and performance improvement program. Additionally, hospitals are expected to report serious • Define an adverse drug reaction. ADRs (as defined by the Food and Drug Administration • Discuss the detection of adverse [FDA]) to the FDA’s MedWatch program and ADRs to vaccines to the FDA’s Vaccine Adverse Events Reporting drug reactions. System (VAERS). • Discuss the assessment of adverse drug reactions. Defining Adverse Drug Reactions To recognize and assess ADRs, there must be a defini- tion of what constitutes an ADR. Examples of commonly used definitions are discussed in the following text. The FDA defines a serious adverse reaction as one in which “the patient outcome is death, life threat- ening (real risk of dying), hospitalization (initial or prolonged), disability (significant, persistent, or perma- nent), congenital anomaly, or required intervention to prevent permanent impairment or damage.”1 The American Society of Health-System Pharma- cists (ASHP) defines a ADR as “any unexpected, unin- tended, undesired, or excessive response to a drug that • requires discontinuing the drug (therapeutic or diagnostic) • requires changing the drug therapy • requires modifying the dose (except for minor dosage adjustments) • necessitates admission to a hospital 546 Competence Assessment Tools for Health-System Pharmacies • prolongs stay in a healthcare facility routine observation and assessment.
  • Aabcde System (Adverse Events of Type A, B, C, D, E)

    Aabcde System (Adverse Events of Type A, B, C, D, E)

    ABCDE SYSTEM (ADVERSE EVENTS OF TYPE A, B, C, D, E) HISTORY Hurwitz and Wade proposed many years ago four categories of adverse events (Br Med J 1969; Mar 1(643):531). The first two mechanisms have been combined A under category A and the second two mechanisms under category B. I Side effect I Excess effect I Allergy (hypersensitivity) I Idiosyncrasy DeSwarte classified adverse drug reactions (ADRs) into eight categories (Arch Intern Med 1986;146:649): I Overdose I Side effect I Secondary, indirect effect I Interaction I Intolerance I Idiosyncrasy (primary toxicity) I Allergy I Pseudoallergy (anaphylactoid) Note that overdose and interaction are risk factors and the indirect or second- ary effect is a physiologic consequence. Further information can be found in Meyboom (PEDS 1997;16:355) and in Royer (PEDS 1997;6:S43). TYPE A ADVERSE EVENT Rawlins and Thompson of Newcastle, Great Britain, have classified adverse events into type A and type B on the basis of the mechanism of action. A type A event is one that is due to an extension of the active pharmacologic properties of the drug (A indicates augmented). They are also called predictable or anticipated events. They are generally less severe and more frequent than type B events. This augmented pharmacologic action may occur at the targeted receptors or at other nontargeted receptors producing lateral effects, parallel effects, or side effects. They are usually detected during the clinical trials done before marketing. There are two subclasses: ◗ Exaggerated Desired Effect The undesirable exaggeration of a desired pharmacologic effect after a normal dose in a susceptible subject or after a higher than normal dose.
  • Stembook 2018.Pdf

    Stembook 2018.Pdf

    The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.