DOCSLIB.ORG

Superiority of Ibutilide (A New Class III Agent) Over

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Superiority of Ibutilide (A New Class III Agent) Over 568 Heart 1998;79:568–575 Superiority of ibutilide (a new class III agent) over DL-sotalol in converting atrial flutter and atrial Heart: first published as 10.1136/hrt.79.6.568 on 1 June 1998. Downloaded from fibrillation M A Vos, S R Golitsyn, K Stangl, M Y Ruda, L Van Wijk, J D Harry, K T Perry, P Touboul, G Steinbeck, HJJWellens, for the Ibutilide/Sotalol Comparator Study Group Abstract III drug, under monitored conditions, is a Objective—To compare the eYcacy and potential alternative to currently available safety of a single dose of ibutilide, a new cardioversion options. class III antiarrhythmic drug, with that of (Heart 1998;79:568–575) DL-sotalol in terminating chronic atrial fibrillation or flutter in haemodynami- Keywords: atrial fibrillation; atrial flutter; cally stable patients. antiarrhythmic agents; ibutilide; sotalol Design—Double blind, randomised study. Setting—43 European hospitals. Atrial fibrillation and atrial flutter are the most Patients—308 patients (mean age 60 years, 70% men, 48% with heart disease) with frequently occurring tachycardias in man: sustained atrial fibrillation (n = 251) or prevalence is estimated to be 0.4% for atrial 1–3 atrial flutter (n = 57) (duration three fibrillation and 0.1% for atrial flutter, and hours to 45 days) were randomised to they may increase to 4% in people older than University Hospital, three groups to receive a 10 minute 60 years. Treatment for acute conversion of Maastricht, infusion of 1 mg ibutilide (n = 99), 2 mg these arrhythmias consists of antiarrhythmic Netherlands drugs or electrical cardioversion, or both. MAVos ibutilide (n = 106), or 1.5 mg/kg DL-sotalol HJJWellens (n = 103). Infusion was discontinued at The basic electrophysiological mechanism termination of the arrhythmia. thought to be responsible for atrial flutter and Cardiology Research Main outcome measure—Successful con- fibrillation is that of re-entry, with atrial fibril- Centre, Moscow, version of atrial fibrillation or flutter, lation being caused by multiple independent Russia defined as termination of arrhythmia re-entry wavelets, and atrial flutter by one large S R Golitsyn http://heart.bmj.com/ 1–5 M Y Ruda within one hour of treatment. circuit often located within the right atrium. Results—Both drugs were more eVective In both instances prolongation of the Humholdt University, against atrial flutter than against atrial wavelength45 (the product of conduction Berlin, Germany fibrillation. Ibutilide was superior to DL- velocity of the impulse and the refractory K Stangl sotalol for treating atrial flutter (70% and period) may cause conversion from atrial St Chr Ziekenhuis 56% v 19%), while the high dose of arrhythmia to sinus rhythm. On the basis of this Refaja, Stadskanaal, ibutilide was more eVective for treating principle class III antiarrhythmic agents, which Netherlands atrial fibrillation than DL-sotalol (44% v increase duration of the action potential and L Van Wijk on September 27, 2021 by guest. Protected copyright. 11%) and the lower dose of ibutilide (44% v the refractory period of atrial muscle without 20%, p < 0.01). The mean (SD) time to Pharmacia & Upjohn, having much influence on conduction velocity, Crawley, West Sussex, arrhythmia termination was 13 (7) min- may help to restore sinus rhythm in patients UK utes with 2 mg ibutilide, 19 (15) minutes with atrial flutter and fibrillation.6–12 The J D Harry with 1 mg ibutilide, and 25 (17) minutes precise electrophysiological mechanism by with DL-sotalol. In all patients, the dura- which class III agents exert their beneficial Pharmacia & Upjohn, tion of arrhythmia before treatment was a Kalamazoo, Michigan, eVect remains speculative. USA predictor of arrhythmia termination, al- Ibutilide fumarate (U-70226E) is a new class though this was less obvious in the group KTPerry III agent for acute conversion of atrial flutter that received 2 mg ibutilide. This dose and fibrillation that has recently been intro- Hospitaux de Lyon, converted almost 48% of atrial fibrillation duced in the US.13–17 Introduction in Europe Lyon, France that was present for more than 30 days. P Touboul will take place throughout 1998. Preclinical Concomitant use of digitalis or nifedipine and prolongation of the QTc interval were animal studies have shown that ibutilide Klinikum Grosehadern prolongs duration of the action potential and of the University of not predictive of arrhythmia termination. Munich, Germany Bradycardia (6.5%) and hypotension the eVective refractory period of the atrium and G Steinbeck (3.7%) were more common side eVects ventricle, thereby preventing and suppressing with DL-sotalol. Of 211 patients given ibu- (the induction of) atrial and ventricular Correspondence to: arrhythmias.18–21 Ibutilide is available only as an Dr M A Vos, Department of tilide, two (0.9%) who received the higher Cardiology, Cardiovascular dose developed polymorphic ventricular intravenous preparation because of poor bio- Research Institute availability caused by a large first pass eVect Maastricht, University tachycardia, one of whom required direct Hospital Maastricht, PO Box current cardioversion. during oral administration. 5800, 6202 AZ Maastricht, Conclusion—Ibutilide (given in 1 or 2 mg DL-sotalol combines class III antiarrhythmic Netherlands. doses over 10 minutes) is highly eVective activity with â adrenoceptor blocking action Accepted for publication for rapidly terminating persistent atrial and is available in many countries as an 24 November 1997 fibrillation or atrial flutter. This new class intravenous formulation. Because it is widely EYcacy of ibutilide and sotalol in atrial arrhythmias 569 Table 1 Number of evaluable patients disease, myocardial infarction or cardiac sur- gery within the previous 30 days, known sinus Ibutilide fumarate node dysfunction, second or third degree Heart: first published as 10.1136/hrt.79.6.568 on 1 June 1998. Downloaded from Arrhythmia 1mg 2mg DL-Sotalol Total atrioventricular (AV) block, bundle branch block, WolV-Parkinson-White syndrome Atrial flutter 16 20 21 57 and/or torsade de pointes were not included. Atrial fibrillation 83 86 82 251 Concurrent treatment with verapamil, diltiazem, or drugs that prolong the QT inter- used for the treatment of atrial arrhythmias in val was not allowed. Treatment with class I or Europe,11 12 this drug was chosen as a compara- III antiarrhythmic agents or with â adrenocep- tor. tor blocking agents was discontinued for more The European multicentre study reported than five half lives before enrolment. Antico- here compares the safety and eYcacy of agulation was the responsibility of the investi- intravenous ibutilide with that of intravenous gators. DL-sotalol in the acute termination of sustained The following information was collected to atrial flutter or fibrillation. identify eligible patients: medical history (in- cluding earlier episodes of atrial fibrillation or atrial flutter and treatment, and time of onset Methods of the current arrhythmic episode), physical STUDY DESIGN This multicentre trial was a prospective, double examination (including blood pressure), 12 blind, randomised, parallel group comparison lead ECG, and laboratory evaluation (includ- of two doses of ibutilide with a single dose of ing digitalis concentrations). DL-sotalol in haemodynamically stable patients who had recent onset sustained atrial flutter or STUDY MEDICATION fibrillation. Recent onset was defined as Patients were randomised to receive 1 mg ibu- continuous atrial flutter or fibrillation for tilide, 2 mg ibutilide, or 1.5 mg/kg DL-sotalol. longer than three hours but less than 45 days. Drugs were prepared in ampules of 25 ml of All centres obtained ethics committee approval which 20 ml was given as a single 10 minute and all patients gave informed consent—319 intravenous infusion using a similar infusion patients were treated at 40 diVerent sites. rate. Blinding was maintained by the drug The protocol intended to enrol 300 patients being prepared by an individual not responsi- equally distributed between the two arrhythmia ble for making assessments. Patients with atrial groups. This objective was not achieved, flutter and fibrillation were separately ran- however, because of the slow recruitment of domised to one of the treatment modes. patients with flutter. A total of 300 patients with both arrhythmias was estimated to detect http://heart.bmj.com/ adiVerence of 17% between both doses of ibu- OBSERVATIONS AND EVALUATIONS At least 15 minutes before administration of tilide combined and DL-sotalol, or 20% be- the drug, continuous ECG monitoring was tween one dose of ibutilide and DL-sotalol (p < 0.05, power 80%). started and continued until seven hours had passed after the start of drug infusion. A Holter recording was made during an additional 24 ELIGIBILITY CRITERIA hours if conversion to sinus rhythm occurred. Patients older than 18 years with recent onset ECGs were recorded at 30 minutes, and one on September 27, 2021 by guest. Protected copyright. sustained atrial flutter or fibrillation were eligi- and seven hours (for patients who were ble when they: were haemodynamically stable successfully treated) after the start of infusion. (systolic blood pressure > 90 mm Hg and The haemodynamic status of the patient was diastolic blood pressure < 105 mm Hg); had a regularly checked by measuring heart rate and normal serum potassium concentration blood pressure every five minutes for 15 (> 4 mEq/l); had a ventricular rate of > 60 minutes before the end of infusion, and at 10 beats/min; and had a rate corrected QT minute intervals for 50 minutes and then interval of no more than 440 ms in their 12 hourly for seven hours. Blood and urine were lead electrocardiogram (ECG). Patients with collected before drug infusion and seven hours hyperthyroidism, or with a history or evidence later for routine safety laboratory evaluations of of unstable angina pectoris, bronchospastic haematological and biochemical variables. Table 2 Demographic and baseline characteristics This seven hour observation period was selected arbitrarily on the basis that side effects Ibutilide have been reported to occur within this period, 1 mg (n = 102) 2 mg (n = 109) Sotalol (n = 108) and it was convenient in the daily logistics of the hospital.
Load more

Recommended publications
  • Table 2. 2012 AGS Beers Criteria for Potentially
    Table 2. 2012 AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults Strength of Organ System/ Recommendat Quality of Recomm Therapeutic Category/Drug(s) Rationale ion Evidence endation References Anticholinergics (excludes TCAs) First-generation antihistamines Highly anticholinergic; Avoid Hydroxyzin Strong Agostini 2001 (as single agent or as part of clearance reduced with e and Boustani 2007 combination products) advanced age, and promethazi Guaiana 2010 Brompheniramine tolerance develops ne: high; Han 2001 Carbinoxamine when used as hypnotic; All others: Rudolph 2008 Chlorpheniramine increased risk of moderate Clemastine confusion, dry mouth, Cyproheptadine constipation, and other Dexbrompheniramine anticholinergic Dexchlorpheniramine effects/toxicity. Diphenhydramine (oral) Doxylamine Use of diphenhydramine in Hydroxyzine special situations such Promethazine as acute treatment of Triprolidine severe allergic reaction may be appropriate. Antiparkinson agents Not recommended for Avoid Moderate Strong Rudolph 2008 Benztropine (oral) prevention of Trihexyphenidyl extrapyramidal symptoms with antipsychotics; more effective agents available for treatment of Parkinson disease. Antispasmodics Highly anticholinergic, Avoid Moderate Strong Lechevallier- Belladonna alkaloids uncertain except in Michel 2005 Clidinium-chlordiazepoxide effectiveness. short-term Rudolph 2008 Dicyclomine palliative Hyoscyamine care to Propantheline decrease Scopolamine oral secretions. Antithrombotics Dipyridamole, oral short-acting* May
    [Show full text]
  • Arrhythmias in the Intensive Care Patient Hans-Joachim Trappe, Bodo Brandts and Peter Weismueller
    Arrhythmias in the intensive care patient Hans-Joachim Trappe, Bodo Brandts and Peter Weismueller Purpose of review ventricular fibrillation. The use of automatic external Atrial fibrillation, atrial flutter, AV–nodal reentry tachycardia defibrillators by basic life support ambulance providers or first with rapid ventricular response, atrial ectopic tachycardia, and responder in early defibrillation programs has been associated preexcitation syndromes combined with atrial fibrillation or with a significant increase in survival rates. Drugs such as ventricular tachyarrhythmias are typical arrhythmias in intensive lidocaine, procainamide, sotalol, amiodarone, or magnesium care patients. Most frequently, the diagnosis of the underlying were recommended for treatment of ventricular arrhythmia is possible from the physical examination, the tachyarrhythmias in intensive care patients. Amiodarone is a response to maneuvers or drugs, and the 12-lead surface highly efficacious antiarrhythmic agent for many cardiac electrocardiogram. In all patients with unstable hemodynamics, arrhythmias, ranging from atrial fibrillation to malignant immediate DC-cardioversion is indicated. Conversion of atrial ventricular tachyarrhythmias, and seems to be superior to other fibrillation to sinus rhythm is possible using antiarrhythmic antiarrhythmic agents. drugs. Amiodarone has a conversion rate in atrial fibrillation of up to 80%. However, caution in the use of short-term Keywords administration of intravenous amiodarone in critically ill patients atrial fibrillation,
    [Show full text]
  • Safety and Efficacy of Ibutilide in Cardioversion of Atrial Flutter And
    J Am Board Fam Med: first published as 10.3122/jabfm.2011.01.080096 on 5 January 2011. Downloaded from CLINICAL REVIEW Safety and Efficacy of Ibutilide in Cardioversion of Atrial Flutter and Fibrillation Madhuri Nair, MD, Lekha K. George, MD, and Santhosh K. G. Koshy, MD This article reviews the safety and efficacy of ibutilide for use in patients with atrial fibrillation and flut- ter. Ibutilide, a class III antiarrhythmic agent, is primarily used for conversion of atrial flutter and fi- brillation and is a good alternative to electrical cardioversion. Ibutilide has a conversion rate of up to 75% to 80% in recent-onset atrial fibrillation and flutter; the conversion rate is higher for atrial flutter than for atrial fibrillation. It is also safe in the conversion of chronic atrial fibrillation/flutter among patients receiving oral amiodarone therapy. Ibutilide pretreatment facilitates transthoracic defibrilla- tion and decreases the energy requirement of electrical cardioversion by both monophasic and biphasic shocks. Pretreatment with ibutilide before electrical defibrillation has a conversion rate of 100% com- pared with 72% with no pretreatment. Ibutilide is also safe and efficient in the treatment of atrial fibril- lation in patients who have had cardiac surgery, and in accessory pathway–mediated atrial fibrillation where the conversion rate of ibutilide is as high as 95%. There is up to a 4% risk of torsade de pointes and a 4.9% risk of monomorphic ventricular tachycardia. Hence, close monitoring in an intensive care unit setting is warranted during and at least for 4 hours after drug infusion. The anticoagulation strat- egy is the same as for any other mode of cardioversion.(J Am Board Fam Med 2011;24:86–92.) Keywords: Antiarrhythmics, Arrhythmia, Atrial Fibrillation, Cardiovascular Disorders, Cardioversion, Drug Ther- copyright.
    [Show full text]
  • Efficacy and Safety of Ibutilide for the Cardioversion of Atrial Fibrillation: a Systematic Review and Meta- Analysis
    Open Access Austin Surgery Case Reports Review Article Efficacy and Safety of Ibutilide for the Cardioversion of Atrial Fibrillation: A Systematic Review and Meta- Analysis Gong CC1, Tang Y2, Huang Y2 and Liu X2* 1Zhejiang University School of Medicine Children’s Abstract Hospital, China Background: Ibutilide has been approved for cardioversion of Atrial 2Department of Critical Care Medicine, the Affiliated Fibrillation (AF), but its side-effects include a high risk of torsade de pointes, Hospital of Guizhou Medical University, China besides, one recent meta-analysis showed ibutilide was inferior to vernakalant *Corresponding author: Liu X, Department of Critical for conversion (AF<7 days). Hence, the aim of this study is to evaluate the Care Medicine, the Affiliated Hospital of Guizhou Medical efficacy and safety of ibutilide for the cardioversion of AF within 90 days. University, China Methods: The Embase, PubMed, Web of Science, Cochrane Central Received: February 16, 2021; Accepted: March 17, databases and clinical trials.gov were comprehensively searched for relevant 2021; Published: March 24, 2021 studies from January 1991 to May 2020 using the keywords “ibutilide” and “atrial fibrillation”. Only Randomized Controlled Trials (RCTs) comparing ibutilide with placebo or other Anti-Arrhythmic Drugs (AADs) for the termination of AF (duration of AF ≤90 days) were included. The primary outcome was successful cardioversion in response to ibutilide versus placebo or other AADs within 4h. Related adverse events were defined as secondary outcomes. Results: A total of 1712 patients in 13 RCTs met the eligibility criteria. Four trials compared ibutilide to placebo; nine trials compared ibutilide to other active drugs.
    [Show full text]
  • Keeping up with the Pace of Antiarrhythmic Drugs ANNMARIE PALATNIK, APN,BC, MSN Coordinator of Continuing Education • Virtua Health • Marlton, N.J
    D rug File Keeping up with the pace of antiarrhythmic drugs ANNMARIE PALATNIK, APN,BC, MSN Coordinator of Continuing Education • Virtua Health • Marlton, N.J. HAVE YOU NOTICED how challenging it is to Conducting impulses keep pace with the The conduction system of the heart, shown below, begins with the heart’s natural pacemaker, the changing beat of phar- sinoatrial (SA) node. When an impulse leaves the SA node, it travels through the atria along macology? Just as you Bachmann’s bundle and the internodal pathways on its way to the atrioventricular (AV) node. After learn the latest drugs the impulse passes through the AV node, it travels to the ventricles, first down the bundle of His, and classifications, new then along the bundle branches and, finally, down the Purkinje fibers. classes are developed and new drugs added to Bachmann’s bundle classes. Even drugs that have been on the mar- ket a long time can have dosing and indica- SA node tion changes. Antiarrhythmic Internodal tracts drugs, which restore Posterior (Thorel’s) normal rhythm and Middle (Wenckebach’s) conduction to the heart, Anterior are no exception. In this AV node article, I’ll bring you up-to-date on the Bundle of His antiarrhythmics now Right bundle branch available. Left bundle branch Class assignments Most antiarrhythmic drugs used to slow a rapid heart rate are classified according to the Vaughn Williams classification system Purkinje fibers (see Classifying Anti- arrhythmics the Vaughn Williams way). These drugs fall Class I into four general groups in this classification system Sodium channel blockers stop the flow of sodium into with each group having several subgroups.
    [Show full text]
  • Ventricular Tachycardia Drugs Versus Devices John Camm St
    Cardiology Update 2015 Davos, Switzerland: 8-12th February 2015 Ventricular Arrhythmias Ventricular Tachycardia Drugs versus Devices John Camm St. George’s University of London, UK Imperial College, London, UK Declaration of Interests Chairman: NICE Guidelines on AF, 2006; ESC Guidelines on Atrial Fibrillation, 2010 and Update, 2012; ACC/AHA/ESC Guidelines on VAs and SCD; 2006; NICE Guidelines on ACS and NSTEMI, 2012; NICE Guidelines on heart failure, 2008; NICE Guidelines on Atrial Fibrillation, 2006; ESC VA and SCD Guidelines, 2015 Steering Committees: multiple trials including novel anticoagulants DSMBs: multiple trials including BEAUTIFUL, SHIFT, SIGNIFY, AVERROES, CASTLE- AF, STAR-AF II, INOVATE, and others Events Committees: one trial of novel oral anticoagulants and multiple trials of miscellaneous agents with CV adverse effects Editorial Role: Editor-in-Chief, EP-Europace and Clinical Cardiology; Editor, European Textbook of Cardiology, European Heart Journal, Electrophysiology of the Heart, and Evidence Based Cardiology Consultant/Advisor/Speaker: Astellas, Astra Zeneca, ChanRX, Gilead, Merck, Menarini, Otsuka, Sanofi, Servier, Xention, Bayer, Boehringer Ingelheim, Bristol- Myers Squibb, Daiichi Sankyo, Pfizer, Boston Scientific, Biotronik, Medtronic, St. Jude Medical, Actelion, GlaxoSmithKline, InfoBionic, Incarda, Johnson and Johnson, Mitsubishi, Novartis, Takeda Therapy for Ventricular Tachycardia Medical therapy Antiarrhythmic drugs Autonomic management Ventricular tachycardia Monomorphic Polymorphic Ventricular fibrillation Ventricular storms Ablation therapy Device therapy Surgical Defibrillation Catheter Antitachycardia pacing History of Antiarrhythmic Drugs 1914 - Quinidine 1950 - Lidocaine 1951 - Procainamide 1946 – Digitalis 1956 – Ajmaline 1962 - Verapamil 1962 – Disopyramide 1964 - Propranolol 1967 – Amiodarone 1965 – Bretylium 1972 – Mexiletine 1973 – Aprindine, Tocainide 1969 - Diltiazem 1975- Flecainide 1976 – Propafenone Encainide Ethmozine 2000 - Sotalol D-sotalol 1995 - Ibutilide (US) Recainam 2000 – Dofetilide US) IndecainideX Etc.
    [Show full text]
  • Product Monograph
    PRODUCT MONOGRAPH PrCORVERT® (ibutilide fumarate injection) 0.1 mg/mL Antiarrhythmic Agent Pfizer Canada ULC Date of Preparation: 17,300 Trans-Canada Highway 29 March 2019 Kirkland, Quebec H9J 2M5 Control No. 222103 ® TM Pharmacia & Upjohn Company LLC Pfizer Canada ULC, Licensee © Pfizer Canada ULC 2019 PRODUCT MONOGRAPH PrCORVERT® (ibutilide fumarate injection) 0.1mg/mL Antiarrhythmic Agent ACTION AND CLINICAL PHARMACOLOGY CORVERT (ibutilide fumarate injection) is an antiarrhythmic drug with predominantly class III (cardiac action potential prolongation) properties according to the Vaughan Williams Classification. Ibutilide fumarate prolongs action potential duration in isolated adult cardiac myocytes and increases both atrial and ventricular refractoriness in vivo, i.e. class III electrophysiologic effects. Voltage clamp studies indicate that ibutilide at nanomolar concentrations, delays repolarisation by activation of a slow, inward current (predominantly sodium), rather than by blocking outward potassium currents, which is the mechanism by which most other class III antiarrhythmics act. These effects lead to prolongation of atrial and ventricular action potential duration and refractoriness, the predominant electrophysiologic properties of ibutilide in humans that are thought to be the basis for its antiarrhythmic effect. 2 PHARMACODYNAMICS Electrophysiologic Effects: Ibutilide produces mild slowing of the sinus rate and atrioventricular conduction. Ibutilide produces no clinically significant effect on QRS duration at the recommended dosage. Ibutilide produces dose-related prolongation of the QT interval, which is thought to be associated with its antiarrhythmic activity. However, there is no established relationship between plasma concentration and antiarrhythmic activity. In studies in healthy volunteers, intravenous infusions of ibutilide resulted in prolongation of the QT interval that was directly correlated with ibutilide plasma concentration during and after 10-minute and 8-hour infusions.
    [Show full text]
  • FDA Briefing Document Cardiovascular and Renal Drugs
    FDA Briefing Document Cardiovascular and Renal Drugs Advisory Committee (CRDAC) Meeting December 10, 2019 Topic: New Drug Application 22034 Vernakalant Hydrochloride Injection for the Rapid Conversion of Recent Onset Atrial Fibrillation 1 The attached package contains background information prepared by the Food and Drug Administration (FDA) for the panel members of the advisory committee. The FDA background package often contains assessments and/or conclusions and recommendations written by individual FDA reviewers. Such conclusions and recommendations do not necessarily represent the final position of the individual reviewers, nor do they necessarily represent the final position of the Review Division or Office. We have brought New Drug Application 22034, atrial fibrillation for the treatment of recent onset atrial fibrillation, to this Advisory Committee in order to gain the Committee’s insights and opinions on key issues identified by the Agency. The background package may not include all issues relevant to the final regulatory recommendation, and the final determination may be affected by issues not discussed at the advisory committee meeting. The FDA will not issue a final determination on the issues at hand until input from the advisory committee process has been considered and all reviews have been finalized. 2 Table of Contents Glossary .......................................................................................................................................... 8 1. Introduction ..........................................................................................................................
    [Show full text]
  • PHARMACY TIMES by IEHP PHARMACEUTICAL SERVICES DEPARTMENT February 11, 2013
    PHARMACY TIMES BY IEHP PHARMACEUTICAL SERVICES DEPARTMENT February 11, 2013 The Centers for Medicare and Medicaid Services (CMS) developed performance and quality measures to help Medicare beneficiaries make informed decisions regarding health and prescription drug plans. As part of this effort, CMS adopted measures for High Risk Medication (HRM) endorsed by the Pharmacy Quality Alliance (PQA) and the National Quality Forum (NQF). The HRM was developed using existing HEDIS measurement “Drugs to be avoided in the elderly”. The HRM rate analyzes the percentage of Medicare Part D beneficiaries 65 years or older who have received prescriptions for drugs with a high risk of serious side effects in the elderly. In order to advance patient safety, IEHP will be identifying members over 65 and currently on one of the medications identified in Table 1. Providers will be receiving a list of these members from IEHP on an ongoing basis. IEHP asks providers to review their member’s current drug regimen and safety risk and make any appropriate changes when applicable. Table 1: Medications identified by CMS to be high risk in the elderly: Drug Class Drug Safety Concerns IEHP Formulary Alternative(s) Acetylcholinesterase Donepezil (in patients Orthostatic hypotension or Memantine Inhibitor with syncope) bradycardia Amphetamines Dextroamphetamine CNS stimulation Weight Control: Diet Lisdextroamphetamine & lifestyle Diethylpropion modification Methylphenidate Phentermine Depression: mirtazapine, trazodone Analgesic Pentazocine Confusion, hallucination, Mild Pain: (includes Meperidine delirium, fall, fracture APAP combination Tramadol Lowers seizure threshold medications) Aspirin > 325 mg/day GI bleeding/peptic ulcer, edema Mod-Severe Pain Diflunisal may worsen heart failure Norco Etodolac Vicodin Fenoprofen Percocet Ketoprofen Morphine Meclofenamate Mefenamic acid Nabumetone 303 E.
    [Show full text]
  • FDA Listing of Established Pharmacologic Class Text Phrases January 2021
    FDA Listing of Established Pharmacologic Class Text Phrases January 2021 FDA EPC Text Phrase PLR regulations require that the following statement is included in the Highlights Indications and Usage heading if a drug is a member of an EPC [see 21 CFR 201.57(a)(6)]: “(Drug) is a (FDA EPC Text Phrase) indicated for Active Moiety Name [indication(s)].” For each listed active moiety, the associated FDA EPC text phrase is included in this document. For more information about how FDA determines the EPC Text Phrase, see the 2009 "Determining EPC for Use in the Highlights" guidance and 2013 "Determining EPC for Use in the Highlights" MAPP 7400.13.
    [Show full text]
  • Comparison of the Effects of DC031050, a Class III Antiarrhythmic Agent, on Herg Channel and Three Neuronal Potassium Channels
    npg Acta Pharmacologica Sinica (2012) 33: 728–736 © 2012 CPS and SIMM All rights reserved 1671-4083/12 $32.00 www.nature.com/aps Original Article Comparison of the effects of DC031050, a class III antiarrhythmic agent, on hERG channel and three neuronal potassium channels Ping LI1, Hai-feng SUN1, Ping-zheng ZHOU1, Chao-ying MA2, Guo-yuan HU1, Hua-liang JIANG1, Min LI1, Hong LIU1, *, Zhao- bing GAO1, * 1State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; 2Life Science and Engineering College of Southwest Jiaotong University, Chengdu 610031, China Aim: This study was conducted to test the selectivity of DC031050 on cardiac and neuronal potassium channels. Methods: Human ether-à-go-go related gene (hERG), KCNQ and Kv1.2 channels were expressed in CHO cells. The delayed rectifier potassium current (IK) was recorded from dissociated hippocampal pyramidal neurons of neonatal rats. Whole-cell voltage patch clamp was used to record the voltage-activated potassium currents. Drug-containing solution was delivered using a RSC-100 Rapid Solution Changer. Results: Both DC031050 and dofetilide potently inhibited hERG currents with IC50 values of 2.3±1.0 and 17.9±1.2 nmol/L, respectively. DC031050 inhibited the IK current with an IC50 value of 2.7±1.5 μmol/L, which was >1000 times the concentration required to inhibit hERG current. DC031050 at 3 μmol/L did not significantly affect the voltage-dependence of the steady activation, steady inactivation of IK, or the rate of IK from inactivation. Intracellular application of DC031050 (5 μmol/L) was insufficient to inhibit IK.
    [Show full text]
  • First Case of Acute Poisoning with Amiodarone and Flecainide in Attempted Suicide Successfully Managed with Lipid Emulsion Thera
    healthcare Case Report First Case of Acute Poisoning with Amiodarone and Flecainide in Attempted Suicide Successfully Managed with Lipid Emulsion Therapy in the Emergency Department: Case Report and Literature Review Cristina Bologa 1,2, Catalina Lionte 1,2,* , Alexandra Popescu 2, Victorita Sorodoc 1,2 and Laurentiu Sorodoc 1,2 1 Internal Medicine and Clinical Toxicology Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; cristina.bologa@umfiasi.ro (C.B.); victorita.sorodoc@umfiasi.ro (V.S.); laurentiu.sorodoc@umfiasi.ro (L.S.) 2 2nd Medical Clinic, “Sf. Spiridon” Emergency Clinical County Hospital, 700111 Iasi, Romania; [email protected] * Correspondence: catalina.lionte@umfiasi.ro or [email protected]; Tel.: +40-742082318 Abstract: Acute antiarrhythmics poisoning represents a challenge in the Emergency Department (ED). These patients often develop malignant arrhythmias in need of exceptional therapeutic measures in the ICU. We report a 47-year-old patient admitted to the ED 5 h after the ingestion of a large dose of amiodarone and flecainide in a suicide attempt. During their ED stay, the patient developed signs of cardiotoxicity evidenced by electrocardiogram and ventricular arrhythmias. The toxicological results showed a level of 4.8 mg/L amiodarone and 2.98 mg/L flecainide. He was successfully treated in the Citation: Bologa, C.; Lionte, C.; ED using a large dose of sodium bicarbonate and lipid emulsion therapy. After hospital admission, Popescu, A.; Sorodoc, V.; Sorodoc, L. First Case of Acute Poisoning with he remained stable, with no need for exceptional therapeutic measures such as mechanical circulatory Amiodarone and Flecainide in support, cardiac pacing or ECMO.
    [Show full text]