Managing Drug-Induced QT Prolongation in Clinical Practice Rani Khatib ,1,2,3 Fatima R N Sabir,1 Caroline Omari,1 Chris Pepper,3 Muzahir Hassan Tayebjee3

Total Page:16

File Type:pdf, Size:1020Kb

Managing Drug-Induced QT Prolongation in Clinical Practice Rani Khatib ,1,2,3 Fatima R N Sabir,1 Caroline Omari,1 Chris Pepper,3 Muzahir Hassan Tayebjee3 Postgrad Med J: first published as 10.1136/postgradmedj-2020-138661 on 29 October 2020. Downloaded from Review Managing drug-induced QT prolongation in clinical practice Rani Khatib ,1,2,3 Fatima R N Sabir,1 Caroline Omari,1 Chris Pepper,3 Muzahir Hassan Tayebjee3 1Medicines Management & ABSTRACT been associated with increases in the QT interval.23 Pharmacy Services, Leeds Many drug therapies are associated with prolongation of Nonetheless, LQTS is typically rare, with an esti- Teaching Hospitals NHS Trust, – Leeds, UK the QT interval. This may increase the risk of Torsades de mated prevalence of approximately 1 in 2000 2500 4 2Leeds Institute of Pointes (TdP), a potentially life-threatening cardiac live births. Many patients are asymptomatic and Cardiovascular and Metabolic arrhythmia. As the QT interval varies with a change in thus congenital LQTS is often discovered inciden- Medicine, University of Leeds, heart rate, various formulae can adjust for this, tally on an ECG, by family history, or after even- Leeds, UK 2 3 producing a ‘corrected QT’ (QTc) value. Normal QTc Cardiology Department, Leeds tually experiencing symptoms such as syncope. Teaching Hospitals NHS Trust, intervals are typically <450 ms for men and <460 ms for Acquired QT prolongation is more prevalent than Leeds, UK women. For every 10 ms increase, there is a ~5% the congenital form and is often a result of structural increase in the risk of arrhythmic events. When heart disease (eg, myocardial infarction, heart fail- Correspondence to prescribing drugs associated with QT prolongation, ure, left ventricular hypertrophy) and drugs that Rani Khatib, Cardiology three key factors should be considered: patient-related prolong the QT interval.5 Many other individual Department, Leeds, UK; risk factors (eg, female sex, age >65 years, uncorrected [email protected] risk factors, detailed later, may also predispose to electrolyte disturbances); the potential risk and degree the prolongation of QT interval.6 of QT prolongation associated with the proposed drug; Received 11 July 2020 Whatever the underlying cause, prolongation Revised 14 September 2020 and co-prescribed medicines that could increase the risk of the QT interval is clinically significant. Accepted 24 September 2020 of QT prolongation. To support clinicians, who are likely Syncope, cardiac arrest and sudden death typi- to prescribe such medicines in their daily practice, we cally increase with increasing QT although assess- developed a simple algorithm to help guide clinical ment is complicated by the relationship being management in patients who are at risk of QT non-linear (figure 2).78QT prolongation may prolongation/TdP, those exposed to QT-prolonging be accompanied by arrhythmogenic after- medication or have QT prolongation. depolarisations, and predisposes patients to a condition known as Torsades de Pointes (TdP), a potentially life-threatening form of polymorphic ventricular tachycardia.910For INTRODUCTION some individuals, TdP may occur with modest The QT interval is the time from the onset of ven- QT prolongation, whereas others may experience 1 http://pmj.bmj.com/ tricular depolarisation to the end of ventricular no effects even with markedly prolonged QT. repolarisation; the latter accounting for the majority There are multiple factors that can increase the 11 of the interval as depolarisation in the absence of risk of TdP (table 1). Many are not modifiable and conduction disease is rapid (figure 1).1 The under- hence not amenable to specific medical interven- lying physiological processes are a result of move- tion. However, the most common environmental ment of sodium, potassium and calcium via specific stressor resulting in acquired LQTS is the use of receptors located in the cell membrane and endo- particular drug therapies,12 which can often be on September 26, 2021 by guest. Protected copyright. plasmic reticulum. Sodium channels are mainly modified to reduce the risk of QT interval prolonga- responsible for depolarisation; however, the late tion and hence of TdP. sodium current contributes to repolarisation. The mechanisms that underlie the impact of cer- Calcium channels are important in maintaining the tain drugs on the QT interval have not been fully plateau phase of the action potential, and potassium elucidated. However, in most instances, it is thought channels play a major role in repolarisation. to relate to effects on specific potassium channels 9 Abnormalities of these receptors can have profound known as rapid delayed rectifiers (IKr). These play ©Author(s)(ortheir effects on the cardiac action potential, for example, a crucial role in cardiac repolarisation and their employer(s)) 2020. Re-use abnormalities in the potassium channels can pro- inhibition extends individual action potentials and permitted under CC BY-NC. long repolarisation.1 The latter can result in QT hence prolongs the QT interval.9 For example, the No commercial re-use. See prolongation on the ECG. antipsychotic medication, haloperidol, is a more rights and permissions. Published by BMJ. Causes of QT prolongation can be divided into specific blocker of the IKr potassium channel and two categories: congenital or acquired. Congenital prolongs QT (by 15–30 ms) in a dose-dependent To cite: Khatib R, Sabir long QTsyndrome (LQTS) is an inherited disease, it manner; and it is known to cause TdP.13 FRN, Omari C, et al. has several forms, and is caused by mutations in the Antiarrhythmic agents such as quinidine and diso- Postgrad Med J Epub ahead genes encoding specific ion-channel subunits or reg- pyramide are known to block both the sodium and of print: [please include Day 2 Month Year]. doi:10.1136/ ulatory proteins. Polymorphisms in various other potassium channels, and are associated with QT postgradmedj-2020- genes—for example that encoding the nitric oxide interval prolongation. TdP was reported with these 138661 synthase 1 adaptor protein (NOS1AP)—have also drugs at therapeutic or subtherapeutic doses.13 Khatib R, et al. Postgrad Med J 2020;0:1–7. doi:10.1136/postgradmedj-2020-138661 1 Postgrad Med J: first published as 10.1136/postgradmedj-2020-138661 on 29 October 2020. Downloaded from Review Table 1 Patient risk factors for Torsades de pointes with drug-induced QT prolongation.10 14 15 Non-modifiable Potentially modifiable ► Congenital long QT syndrome* ► Bradycardia ► QT-prolonging drugs should not ► Uncorrected electrolyte distur- be used in these patients bances (hypokalaemia, hypo- ► Structural heart diseases, such magnesaemia, hypocalcaemia) as heart failure (low ventricular ► Recent cardioversion with ejection fraction), left ventricular a QT-prolonging drug hypertrophy, and myocardial infarction ► Thyroid disease (not treated); more common with hypothyroidism ► Impaired hepatic or renal func- tion (could affect drug metabolism) ► Female sex ► Age >65 years *Congenital long QT syndrome is rare (estimated prevalence: ~1 in 2000–2500 infants) but is associated with a risk of arrhythmia and premature sudden death.4 To reduce the risk of TdP, healthcare professionals should be aware of drugs that can prolong the QT interval. However, few recommendations exist for managing the risk of drug-induced QT prolongation in clinical practice. Many studies have intro- Figure 1 Measurement of the QT interval. duced risk models for predicting prolongation of the QT – interval/TdP,16 18 but these tools are often not generalisable across all populations. They also do not provide guidance on how to manage high-risk cases once identified. In this review, we provide guidance on what should be considered when prescrib- ing QT-prolonging medications in any speciality, in order to rationalise the associated risks and benefits and support clini- cians in making clinical judgements in a holistic manner. We also describe the recommended steps in managing QT prolongation if it arises. WHAT IS A NORMAL QT INTERVAL AND WHAT LEVEL OF http://pmj.bmj.com/ INCREASE IS SIGNIFICANT? The QT interval should be assessed from a good-quality ECG readout that is free from noise artefacts and has a stable baseline. It should be determined as a mean value based on at least 3–5 cardiac cycles.19 It is important to review the entire ECG before specifically on September 26, 2021 by guest. Protected copyright. assessing the QT interval, to ensure that other conditions such as bradycardia, myocardial infarction or cardiomyopathy are not responsible for any changes in QT. In addition, the QT interval cannot be assessed in the usual way in patients whose QRS dura- 19 Figure 2 Non-linear relationship in the estimated rate of patients being tion is abnormal (eg, those with bundle branch block). free of cardiac events at 40 years of age and QT interval corrected for Even in patients with an otherwise normal ECG readout, ana- heart rate (QTc). The study included 647 patients from families with lysis of the QT interval is made more difficult by substantial 1 long-QT syndrome divided into four quartiles based on QTc interval. natural variability. For example, it is typically prolonged at ‘Cardiac events’ were defined as the occurrence of syncope, cardiac arrest slower heart rates and shortened when heart rate is increased. or sudden death, and these increased non-linearly with increasing QTc. However, various formulae have been proposed to adjust for 1 Data were extracted from a Kaplan–Meier survival graph presented in these variations, thus producing a ‘corrected QT’ (QTc) value. Priori et al (2003)8 using WebPlotDigitizer v3.9. The most frequently
Recommended publications
  • Research in Your Backyard Developing Cures, Creating Jobs
    Research in Your Backyard Developing Cures, Creating Jobs PHARMACEUTICAL CLINICAL TRIALS IN ILLINOIS Dots show locations of clinical trials in the state. Executive Summary This report shows that biopharmaceutical research com- Quite often, biopharmaceutical companies hire local panies continue to be vitally important to the economy research institutions to conduct the tests and in Illinois, and patient health in Illinois, despite the recession. they help to bolster local economies in communities all over the state, including Chicago, Decatur, Joliet, Peoria, At a time when the state still faces significant economic Quincy, Rock Island, Rockford and Springfield. challenges, biopharmaceutical research companies are conducting or have conducted more than 4,300 clinical For patients, the trials offer another potential therapeutic trials of new medicines in collaboration with the state’s option. Clinical tests may provide a new avenue of care for clinical research centers, university medical schools and some chronic disease sufferers who are still searching for hospitals. Of the more than 4,300 clinical trials, 2,334 the medicines that are best for them. More than 470 of the target or have targeted the nation’s six most debilitating trials underway in Illinois are still recruiting patients. chronic diseases—asthma, cancer, diabetes, heart dis- ease, mental illnesses and stroke. Participants in clinical trials can: What are Clinical Trials? • Play an active role in their health care. • Gain access to new research treatments before they In the development of new medicines, clinical trials are are widely available. conducted to prove therapeutic safety and effectiveness and compile the evidence needed for the Food and Drug • Obtain expert medical care at leading health care Administration to approve treatments.
    [Show full text]
  • Association of Oral Anticoagulants and Proton Pump Inhibitor Cotherapy with Hospitalization for Upper Gastrointestinal Tract Bleeding
    Supplementary Online Content Ray WA, Chung CP, Murray KT, et al. Association of oral anticoagulants and proton pump inhibitor cotherapy with hospitalization for upper gastrointestinal tract bleeding. JAMA. doi:10.1001/jama.2018.17242 eAppendix. PPI Co-therapy and Anticoagulant-Related UGI Bleeds This supplementary material has been provided by the authors to give readers additional information about their work. Downloaded From: https://jamanetwork.com/ on 10/02/2021 Appendix: PPI Co-therapy and Anticoagulant-Related UGI Bleeds Table 1A Exclusions: end-stage renal disease Diagnosis or procedure code for dialysis or end-stage renal disease outside of the hospital 28521 – anemia in ckd 5855 – Stage V , ckd 5856 – end stage renal disease V451 – Renal dialysis status V560 – Extracorporeal dialysis V561 – fitting & adjustment of extracorporeal dialysis catheter 99673 – complications due to renal dialysis CPT-4 Procedure Codes 36825 arteriovenous fistula autogenous gr 36830 creation of arteriovenous fistula; 36831 thrombectomy, arteriovenous fistula without revision, autogenous or 36832 revision of an arteriovenous fistula, with or without thrombectomy, 36833 revision, arteriovenous fistula; with thrombectomy, autogenous or nonaut 36834 plastic repair of arteriovenous aneurysm (separate procedure) 36835 insertion of thomas shunt 36838 distal revascularization & interval ligation, upper extremity 36840 insertion mandril 36845 anastomosis mandril 36860 cannula declotting; 36861 cannula declotting; 36870 thrombectomy, percutaneous, arteriovenous
    [Show full text]
  • Five Years of the Cipa Project (2013–2018) REVIEW - What Did We Learn? Dong-Seok Yim* Department of Clinical Pharmacology and Therapeutics, Seoul St
    2018;26(4):145-149 TCP Transl Clin Pharmacol https://doi.org/10.12793/tcp.2018.26.4.145 Five years of the CiPA project (2013–2018) REVIEW - what did we learn? Dong-Seok Yim* Department of Clinical Pharmacology and Therapeutics, Seoul St. Mary’s Hospital, Seoul 06591, Korea, PIPET (Pharmacometrics Institute for Practical Education and Training), College of Medicine, The Catholic University of Korea, Seoul 06591, Korea *Correspondence: D. S. Yim; Tel: +82-2-2258-7327, E-mail: [email protected] Cases of drug-induced QT prolongation and sudden cardiac deaths resulted in market withdrawal Keywords of many drugs and world-wide regulatory changes through accepting the ICH guidelines E14 and Cardiomyocytes, S7B. However, because the guidelines were not comprehensive enough to cover the electrophysi- CiPA, hERG, ological changes by drug-induced cardiac ion channel blocking, CiPA was initiated by experts in In silico, governments and academia in the USA, Europe, and Japan in 2013. Five years have passed since the JT peak launch of the CiPA initiative that aimed to improve the current ICH guidelines. This report reviews pISSN: 2289-0882 the current achievements of the CiPA initiative and explores unresolved issues. eISSN: 2383-5427 tive include the regulators FDA, European Medicines Agency, Background Health Canada, Japan’s Pharmaceuticals and Medical Devices Cases of drug-induced torsade de Pointes (TdP) that were Agency, industry, and academia. The initiative also coordinates reported in the 1990s and 2000s resulted in the market with- with several organizations such as the Health and Environmen- drawal of many drugs.[1] Because QTc interval prolongation tal Science Institute, the Safety Pharmacology Society, and the by blocking the cardiac hERG channel was reported to provoke Cardiac Safety Research Consortium.
    [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]
  • Pharmaceutical Appendix to the Tariff Schedule 2
    Harmonized Tariff Schedule of the United States (2007) (Rev. 2) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2007) (Rev. 2) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. ABACAVIR 136470-78-5 ACIDUM LIDADRONICUM 63132-38-7 ABAFUNGIN 129639-79-8 ACIDUM SALCAPROZICUM 183990-46-7 ABAMECTIN 65195-55-3 ACIDUM SALCLOBUZICUM 387825-03-8 ABANOQUIL 90402-40-7 ACIFRAN 72420-38-3 ABAPERIDONUM 183849-43-6 ACIPIMOX 51037-30-0 ABARELIX 183552-38-7 ACITAZANOLAST 114607-46-4 ABATACEPTUM 332348-12-6 ACITEMATE 101197-99-3 ABCIXIMAB 143653-53-6 ACITRETIN 55079-83-9 ABECARNIL 111841-85-1 ACIVICIN 42228-92-2 ABETIMUSUM 167362-48-3 ACLANTATE 39633-62-0 ABIRATERONE 154229-19-3 ACLARUBICIN 57576-44-0 ABITESARTAN 137882-98-5 ACLATONIUM NAPADISILATE 55077-30-0 ABLUKAST 96566-25-5 ACODAZOLE 79152-85-5 ABRINEURINUM 178535-93-8 ACOLBIFENUM 182167-02-8 ABUNIDAZOLE 91017-58-2 ACONIAZIDE 13410-86-1 ACADESINE 2627-69-2 ACOTIAMIDUM 185106-16-5 ACAMPROSATE 77337-76-9
    [Show full text]
  • Patent Application Publication ( 10 ) Pub . No . : US 2019 / 0192440 A1
    US 20190192440A1 (19 ) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2019 /0192440 A1 LI (43 ) Pub . Date : Jun . 27 , 2019 ( 54 ) ORAL DRUG DOSAGE FORM COMPRISING Publication Classification DRUG IN THE FORM OF NANOPARTICLES (51 ) Int . CI. A61K 9 / 20 (2006 .01 ) ( 71 ) Applicant: Triastek , Inc. , Nanjing ( CN ) A61K 9 /00 ( 2006 . 01) A61K 31/ 192 ( 2006 .01 ) (72 ) Inventor : Xiaoling LI , Dublin , CA (US ) A61K 9 / 24 ( 2006 .01 ) ( 52 ) U . S . CI. ( 21 ) Appl. No. : 16 /289 ,499 CPC . .. .. A61K 9 /2031 (2013 . 01 ) ; A61K 9 /0065 ( 22 ) Filed : Feb . 28 , 2019 (2013 .01 ) ; A61K 9 / 209 ( 2013 .01 ) ; A61K 9 /2027 ( 2013 .01 ) ; A61K 31/ 192 ( 2013. 01 ) ; Related U . S . Application Data A61K 9 /2072 ( 2013 .01 ) (63 ) Continuation of application No. 16 /028 ,305 , filed on Jul. 5 , 2018 , now Pat . No . 10 , 258 ,575 , which is a (57 ) ABSTRACT continuation of application No . 15 / 173 ,596 , filed on The present disclosure provides a stable solid pharmaceuti Jun . 3 , 2016 . cal dosage form for oral administration . The dosage form (60 ) Provisional application No . 62 /313 ,092 , filed on Mar. includes a substrate that forms at least one compartment and 24 , 2016 , provisional application No . 62 / 296 , 087 , a drug content loaded into the compartment. The dosage filed on Feb . 17 , 2016 , provisional application No . form is so designed that the active pharmaceutical ingredient 62 / 170, 645 , filed on Jun . 3 , 2015 . of the drug content is released in a controlled manner. Patent Application Publication Jun . 27 , 2019 Sheet 1 of 20 US 2019 /0192440 A1 FIG .
    [Show full text]
  • Mechanism of Drug-Induced Qt Interval Prolongation
    ABSTRACT Torsades de pointes (TdP) is a polymorphic ventricular tachycardia characterized by a distinctive pattern of undulating QRS complexes that twist around the isoelectric line. TdP is usually self-terminating or can subsequently degenerate into ventricular fibrillation, syncope, and sudden death. TdP has been associated with QT interval prolongation of the electrocardiogram; therefore, the QT interval has come to be recognized as a surrogate marker for the risk of TdP. International guidelines have been developed to harmonize both the preclinical and clinical studies for the evaluation of drug-induced TdP. However, currently preclinical in vitro and in vivo methods as well as biomarkers for proarrhythmias have been imperfect in predicting drug-induced TdP in humans. It is clear that relevant biomarkers together with appropriate models are needed to assess the arrhythmic risk of new chemical entities. The goal of the present dissertation is to create rabbit with myocardial failing heart as an in vivo animal model to predict TdP in humans and to determine mechanism(s) underlying TdP in this model. Electrocardiograms were recorded from bipolar transthoracic leads in 7 conscious healthy rabbits previously trained to rest quietly in slings. The RR and QT relationship, ii QT=2.4RR0.72 (r2=0.79, p < 0.001) was obtained by slowed the heart rate with 2.0 mg/kg zatebradine, and the algorithm for removing effect of heart rate on QT is QTc = QT/(RR)0.72. QTc lengthened significantly in all conscious rabbits given intravenous cisapride, dofetilide or haloperidol (p < 0.05), and QTc did not change with DMSO (vehicle control), propranolol or enalaprilat.
    [Show full text]
  • Pharmaceutical Appendix to the Harmonized Tariff Schedule
    Harmonized Tariff Schedule of the United States Basic Revision 3 (2021) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States Basic Revision 3 (2021) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 Table 1. This table enumerates products described by International Non-proprietary Names INN which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service CAS registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known.
    [Show full text]
  • PHARMACEUTICAL APPENDIX to the HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2008) (Rev
    Harmonized Tariff Schedule of the United States (2008) (Rev. 2) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2008) (Rev. 2) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. ABACAVIR 136470-78-5 ACIDUM GADOCOLETICUM 280776-87-6 ABAFUNGIN 129639-79-8 ACIDUM LIDADRONICUM 63132-38-7 ABAMECTIN 65195-55-3 ACIDUM SALCAPROZICUM 183990-46-7 ABANOQUIL 90402-40-7 ACIDUM SALCLOBUZICUM 387825-03-8 ABAPERIDONUM 183849-43-6 ACIFRAN 72420-38-3 ABARELIX 183552-38-7 ACIPIMOX 51037-30-0 ABATACEPTUM 332348-12-6 ACITAZANOLAST 114607-46-4 ABCIXIMAB 143653-53-6 ACITEMATE 101197-99-3 ABECARNIL 111841-85-1 ACITRETIN 55079-83-9 ABETIMUSUM 167362-48-3 ACIVICIN 42228-92-2 ABIRATERONE 154229-19-3 ACLANTATE 39633-62-0 ABITESARTAN 137882-98-5 ACLARUBICIN 57576-44-0 ABLUKAST 96566-25-5 ACLATONIUM NAPADISILATE 55077-30-0 ABRINEURINUM 178535-93-8 ACODAZOLE 79152-85-5 ABUNIDAZOLE 91017-58-2 ACOLBIFENUM 182167-02-8 ACADESINE 2627-69-2 ACONIAZIDE 13410-86-1 ACAMPROSATE
    [Show full text]
  • April Through June 2014
    April through June 2014 Undeclared Drug Ingredient Found in MV5 Days: Updated Warnings—Current Drugs The FDA is advising consumers not to purchase or use MV5 Days, a product promoted and sold for sexual en- hancement. FDA laboratory analysis confirmed that MV5 Public Notification Regarding Male Sexual En- Days contains sildenafil, the active ingredient in the FDA hancement Products: The FDA is advising consumers approved prescription drug Viagra, used to treat ED. This not to purchase or use GoldReallas, Full Throttle On De- undeclared ingredient may interact with nitrates found in mand, 3 Hard Knights, Dick’s Hard Up, Eyeful, Liu Bian Li, some prescription drugs such as nitroglycerin and may products promoted and sold for sexual enhancement on lower blood pressure to dangerous levels. Men with diabe- various websites and in some retail stores. FDA laboratory tes, high blood pressure, high cholesterol, or heart disease analysis confirmed that these products contained the fol- often take nitrates. lowing undeclared drug ingredients: MV5 Days is a product promoted and sold for sexual en- • GoldReallas: sildenafil and thiosildenafil hancement on various websites and in some retail stores. • Full Throttle On Demand: propoxyphenyl sildenafil FDA is recommending that consumers do not purchase or • 3 Hard Knights: sildenafil and thiosildenafil use MV5 Days. (5/16/14) • Dick’s Hard Up: tadalafil • Eyeful: hydroxythiohomosildenafil Lunesta—Next Day Impairments: The FDA has noti- • Liu Bian Li: sildenafil fied health professionals and their medical care organiza- These undeclared ingredients may interact with nitrates tions of a new warning that the insomnia drug Lunesta found in some prescription drugs such as nitroglycerin and (eszopiclone) can cause next-day impairment of driving may lower blood pressure to dangerous levels.
    [Show full text]
  • 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.
    [Show full text]
  • MM&M Takes a Detailed Look at Key Products in the Pipeline
    MM&M takes a detailed look at key products in the pipeline, highlighting the most promising with insights and ratings from Ptop analysts, to IPE provide an overall picture of each therapeutic’s potential value INE 2010 uerosto commodo odionul PROVOCAtiVe AGMM&M’s Pipeline 2010 drawsENTS from the best in drug development, profiling 15 agents with the highest approval probability and brightest commercial prospects. These are the prime near-term launch candidates. The report also provides updates on 202 products in a host of therapeutic areas. Marc Iskowitz reports ualitative change, rather than the quantitative kind, marks best hope to replace warfarin. Then there are the upstarts. Patients this year’s biopharmaceutical pipeline. There has been a shift with rare diseases are finally getting drugs specifically approved for Q in categories poised to yield near-term approvals. And while them. According to a new analysis by the Tufts Center for the Study not the goldmine drug marketers were hoping for, analysts expect of Drug Development, the annual rate of new product approvals the 2010 R&D seam to yield some exciting launch prospects in the worldwide for neglected diseases increased from an average of 1.8 months and years ahead. in 1975-99 to 2.6 in 2000-09. Vaccines and antiviral drugs have also Oncology, a well of innovative approvals in years past, has run seen a resurgence, with physicians talking about a possible cure for relatively dry. “In 2000-2001, we saw Avastin, Tarceva, Sutent, Nexa- hepatitis C and a number of vaccines in the pipeline for ailments var, Gleevec—drugs that revolutionized the way we think about from flu to cancer and diabetes.
    [Show full text]