DOCSLIB.ORG

European Patent Office

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Europäisches Patentamt *EP001336407A1* (19) European Patent Office Office européen des brevets (11) EP 1 336 407 A1 (12) EUROPEAN PATENT APPLICATION published in accordance with Art. 158(3) EPC (43) Date of publication: (51) Int Cl.7: A61K 31/4178, A61K 31/54, 20.08.2003 Bulletin 2003/34 A61K 45/00, A61P 9/12 (21) Application number: 01982846.6 (86) International application number: PCT/JP01/10095 (22) Date of filing: 19.11.2001 (87) International publication number: WO 02/041890 (30.05.2002 Gazette 2002/22) (84) Designated Contracting States: (72) Inventors: AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU • SADA, Toshio SANKYO COMPANY, LIMITED MC NL PT SE TR Shinagawa-ku, Tokyo 140-8710 (JP) • MIZUNO, Makoto SANKYO COMPANY, LIMITED (30) Priority: 21.11.2000 JP 2000354327 Shinagawa-ku, Tokyo 140-8710 (JP) 31.05.2001 JP 2001164009 (74) Representative: (71) Applicant: Sankyo Company, Limited Gibson, Christian John Robert et al Tokyo 103-8426 (JP) MARKS & CLERK, 57/60 Lincoln’s Inn Fields London WC2A 3LS (GB) (54) MEDICINAL COMPOSITIONS (57) [Constitution] EP 1 336 407 A1 Printed by Jouve, 75001 PARIS (FR) (Cont. next page) EP 1 336 407 A1 A pharmaceutical composition comprises an angiotensin II receptor antagonist selected from among compounds having the above general formula (I), pharmacologically acceptable salts thereof, pharmacologically acceptable esters thereof and pharmacologically acceptable salts of said esters, and one or more diuretics. [Effects] The pharmaceutical composition of present invention has an excellent hypotensive effect and low toxicity, and therefore is useful as a medicament for preventing or treating hypertension or heart diseases. 2 EP 1 336 407 A1 Description [Technical field] 5 [0001] The present invention relates to a pharmaceutical composition containing a specific angiotensin II receptor antagonist and one or more diuretics as the active ingredients (particularly a pharmaceutical composition for preventing or treating hypertension), the use of a specific angiotensin II receptor antagonist and one or more diuretics for manu- facturing the pharmaceutical composition (particularly a pharmaceutical composition for preventing or treating hyper- tension), and a method for preventing or treating (particularly treating) diseases (particularly hypertension) by the ad- 10 ministration of a pharmaceutical composition to warm-blooded animals (particularly humans) comprising effective dos- es of a specific angiotensin II receptor antagonist and one or more diuretics. [Background art] 15 [0002] It is known that co-administration of an angiotensin II receptor antagonist and a diuretic is an effective therapy for the prevention or treatment of hypertension (particularly treatment). These pharmaceutical compositions are de- scribed, for example, in WO89/6233, Japanese Patent Application Kokai No. Hei 3-27362 and the like. [0003] However, the effects of a pharmaceutical composition containing a specific angiotensin II receptor antagonist, such as CS-866, and a diuretic remain unknown. 20 [Disclosure of the invention] [0004] Considering that prevention and/or treatment of hypertension are important, the present inventors investigated combinations of various drugs and found that a pharmaceutical composition containing a specific angiotensin II receptor 25 antagonist, such as CS-866, and one or more diuretics exerts excellent anti-hypertensive effects and hence may be useful as a preventative and/or therapeutic agent for hypertension. [0005] The present invention provides a pharmaceutical composition containing a specific angiotensin II receptor antagonist and one or more diuretics as the active ingredients (particularly pharmaceutical compositions for preventing or treating hypertension), the use of a specific angiotensin II receptor antagonist and one or more diuretics for manu- 30 facturing the pharmaceutical compositions (particularly pharmaceutical compositions for preventing or treating hyper- tension), a method for preventing or treating (particularly treating) diseases (particularly hypertension) by the admin- istration of a specific angiotensin II receptor antagonist and one or more diuretics to warm-blooded animals (particularly humans) at effective doses, and a pharmaceutical composition for administering simultaneously or sequentially a spe- cific angiotensin II receptor antagonist and one or more diuretics for preventing or treating hypertension. 35 [0006] The active ingredients of the pharmaceutical composition of this invention include an angiotensin II acceptor antagonist selected from the group consisting of a compound having the following formula (I), pharmacologically ac- ceptable salts thereof, pharmacologically acceptable esters thereof and pharmacologically acceptable salts of said esters; and one or more diuretics. 40 45 50 55 3 EP 1 336 407 A1 5 10 15 20 25 [0007] The compound of formula (I), a salt thereof and the like are known compounds, for example, described in the specification of Japanese Patent Application Kokai No. Hei 5-78328 etc. and the chemical name of the compound of formula (I) is 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[2'-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]imidazol-5-carboxylic acid. 30 [0008] The "pharmacologically acceptable salt" of the compound of formula (I), which is an active ingredient of this invention, includes an alkali metal salt such as sodium salt, potassium salt or lithium salt; an alkaline earth metal salt such as calcium salt or magnesium salt; a metal salt such as aluminum salt, iron salt, zinc salt, copper salt, nickel salt or cobalt salt; or an amine salt such as ammonium salt, t-octylamine salt, dibenzylamine salt, morpholine salt, glu- cosamine salt, phenylglycine alkyl ester salt, ethylenediamine salt, N-methylglucamine salt, guanidine salt, diethyl- 35 amine salt, triethylamine salt, dicyclohexylamine salt, N,N'-dibenzylethylenediamine salt, chloroprocaine salt, procaine salt, diethanolamine salt, N-benzylphenethylamine salt, piperazine salt, tetramethylammonium salt or tris(hydroxyme- thyl)aminomethane salt. An alkali metal salt is preferable and the sodium salt is particularly preferable. [0009] The "pharmacologically acceptable ester" of the compound of formula (I), which is an active ingredient of this invention, is a compound esterified at the carboxyl moiety of the compound of formula (I). A group forming said ester 40 is a group which can be cleaved by a biological process such as hydrolysis in vivo. Such groups include, for example, a(C1-C4)alkoxy-(C1-C4)alkyl group such as methoxymethyl, 1-ethoxyethyl, 1-methyl-1-methoxyethyl, 1-(isopropoxy) ethyl, 2-methoxyethyl, 2-ethoxyethyl, 1,1-dimethyl-1-methoxymethyl, ethoxymethyl, propoxymethyl, isopropoxymethyl, butoxymethyl or t-butoxymethyl; a (C1-C4)alkoxylated (C1-C4)alkoxy-(C1-C4)alkyl group such as 2-methoxyethoxyme- thyl; a (C6-C10)aryloxy-(C1-C4)alkyl group such as phenoxymethyl; a halogenated (C1-C4)alkoxy-(C1-C4)alkyl group 45 such as 2,2,2-trichloroethoxymethyl or bis(2-chloroethoxy)methyl; a (C1-C4)alkoxycarbonyl-(C1-C4)alkyl group such as methoxycarbonylmethyl; a cyano-(C1-C4)alkyl group such as cyanomethyl or 2-cyanoethyl; a (C1-C4)alkylthiomethyl group such as methylthiomethyl or ethylthiomethyl; a (C6-C10)arylthiomethyl such as phenylthiomethyl or naphthylth- iomethyl; a (C1-C4)alkylsulfonyl-(C1-C4) lower alkyl group, which may be optionally substituted with a halogen atom (s), such as 2-methanesulfonylethyl or 2-trifluoromethanesulfonylethyl; a (C6-C10)arylsulfonyl-(C1-C4)alkyl group such 50 as 2-benzenesulfonylethyl or 2-toluenesulfonylethyl; an aliphatic (C1-C7)acyloxy-(C1-C4)alkyl group such as formy- loxymethyl, acetoxymethyl, propionyloxymethyl, butyryloxymethyl, pivaloyloxymethyl, valeryloxymethyl, isovaleryl- oxymethyl, hexanoyloxymethyl, 1-formyloxyethyl, 1-acetoxyethyl, 1-propionyloxyethyl, 1-butyryloxyethyl, 1-pivaloy- loxyethyl, 1-valeryloxyethyl, 1-isovaleryloxyethyl, 1-hexanoyloxyethyl, 2-formyloxyethyl, 2-acetoxyethyl, 2-propiony- loxyethyl, 2-butyryloxyethyl, 2-pivaloyloxyethyl, 2-valeryloxyethyl, 2-isovaleryloxyethyl, 2-hexanoyloxyethyl, 1-formy- 55 loxypropyl, 1-acetoxypropyl, 1-propionyloxypropyl, 1-butyryloxypropyl, 1-pivaloyloxypropyl, 1-valeryloxypropyl, 1-iso- valeryloxypropyl, 1-hexanoyloxypropyl, 1-acetoxybutyl, 1-propionyloxybutyl, 1-butyryloxybutyl, 1-pivaloyloxybutyl, 1-acetoxypentyl, 1-propionyloxypentyl, 1-butyryloxypentyl, 1-pivaloyloxypentyl, or 1-pivaloyloxyhexyl; a (C5-C6)cy- cloalkylcarbonyloxy-(C1-C4)alkyl group such as cyclopentylcarbonyloxymethyl, cyclohexylcarbonyloxymethyl, 1-cy- 4 EP 1 336 407 A1 clopentylcarbonyloxyethyl, 1-cyclohexylcarbonyloxyethyl, 1-cyclopentylcarbonyloxypropyl, 1-cyclohexylcarbonyloxy- propyl, 1-cyclopentylcarbonyloxybutyl or 1-cyclohexylcarbonyloxybutyl; a (C6-C10)arylcarbonyloxy-(C1-C4)alkyl group such as benzoyloxymethyl; a (C1-C6)alkoxycarbonyloxy-(C1-C4)alkyl group such as methoxycarbonyloxymethyl, 1-(methoxycarbonyloxy)ethyl, 1-(methoxycarbonyloxy)propyl, 1-(methoxycarbonyloxy)butyl, 1-(methoxycarbonyloxy) 5 pentyl, 1-(methoxycarbonyloxy)hexyl, ethoxycarbonyloxymethyl, 1-(ethoxycarbonyloxy)ethyl, 1-(ethoxycarbonyloxy) propyl, 1-(ethoxycarbonyloxy)butyl, 1-(ethoxycarbonyloxy)pentyl, 1-(ethoxycarbonyloxy)hexyl, propoxycarbony- loxymethyl, 1-(propoxycarbonyloxy)ethyl, 1-(propoxycarbonyloxy)propyl, 1-(propoxycarbonyloxy)butyl, isopropoxycar- bonyloxymethyl,1-(isopropoxycarbonyloxy)ethyl,1-(isopropoxycarbonyloxy)butyl,butoxycarbonyloxymethyl,1-(butox- ycarbonyloxy)ethyl, 1-(butoxycarbonyloxy)propyl, 1-(butoxycarbonyloxy)butyl,
Recommended publications
  • In Silico Methods for Drug Repositioning and Drug-Drug Interaction Prediction

    In Silico Methods for Drug Repositioning and Drug-Drug Interaction Prediction

    In silico Methods for Drug Repositioning and Drug-Drug Interaction Prediction Pathima Nusrath Hameed ORCID: 0000-0002-8118-9823 Submitted in total fulfilment of the requirements for the degree of Doctor of Philosophy Department of Mechanical Engineering THE UNIVERSITY OF MELBOURNE May 2018 Copyright © 2018 Pathima Nusrath Hameed All rights reserved. No part of the publication may be reproduced in any form by print, photoprint, microfilm or any other means without written permission from the author. Abstract Drug repositioning and drug-drug interaction (DDI) prediction are two fundamental ap- plications having a large impact on drug development and clinical care. Drug reposi- tioning aims to identify new uses for existing drugs. Moreover, understanding harmful DDIs is essential to enhance the effects of clinical care. Exploring both therapeutic uses and adverse effects of drugs or a pair of drugs have significant benefits in pharmacology. The use of computational methods to support drug repositioning and DDI prediction en- able improvements in the speed of drug development compared to in vivo and in vitro methods. This thesis investigates the consequences of employing a representative training sam- ple in achieving better performance for DDI classification. The Positive-Unlabeled Learn- ing method introduced in this thesis aims to employ representative positives as well as reliable negatives to train the binary classifier for inferring potential DDIs. Moreover, it explores the importance of a finer-grained similarity metric to represent the pairwise drug similarities. Drug repositioning can be approached by new indication detection. In this study, Anatomical Therapeutic Chemical (ATC) classification is used as the primary source to determine the indications/therapeutic uses of drugs for drug repositioning.
  • Summary of Product Characteristics

    Summary of Product Characteristics

    Sandoz Business use only Page 1 of 9 1.3.1 spc-label-pl - common-spc – 11,006 20191218 (DE/H/1772/001-002-003 – 155347 - validation) TORASEMIDE 100 MG, 200 MG, 50 MG, TABLET 721-6534.01, 721-6535.01, 721-6536.01 SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE MEDICINAL PRODUCT [Nationally completed name] 50 mg tablets [Nationally completed name] 100 mg tablets [Nationally completed name] 200 mg tablets 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each tablet contains 50 mg of torasemide. Each tablet contains 100 mg of torasemide. Each tablet contains 200 mg of torasemide. For excipients, see section 6.1 3. PHARMACEUTICAL FORM Tablet. 50 mg tablets: White to off-white round tablet. 100 mg tablets: White to off-white round tablet with break notch. The tablet can be divided into equal doses. 200 mg tablets: White to off-white round tablet with cross break notch on both sides. The tablet can be divided into four equal doses. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications The administration of [Nationally completed name] 50 mg/- 100 mg/- 200 mg tablets is exclusively indicated in patients with highly reduced renal function (creatinine clearance less than 20 ml/min and/or serum creatinine concentration greater than 6 mg/dl). For maintenance of residual diuresis in case of severe renal insufficiency – even on dialysis if there is a considerable residual diuresis (more than 200 ml/24 hours) – if oedemas, effusions and/or hypertension exist. Note: [Nationally completed name] 50 mg/- 100 mg/- 200 mg tablets tablets are to be used only in case of highly impaired and not in normal renal function.
  • Comprehensive Screening of Diuretics in Human Urine Using Liquid Chromatography Tandem Mass Spectrometry

    Comprehensive Screening of Diuretics in Human Urine Using Liquid Chromatography Tandem Mass Spectrometry

    id5246609 pdfMachine by Broadgun Software - a great PDF writer! - a great PDF creator! - http://www.pdfmachine.com http://www.broadgun.com AAnnaallyyttiiccaaISllS N : 0974-7419 Volume 13 Issue 7 CCHHEEAnMM IndIIiSaSnT TJoRuRrnYaYl Full Paper ACAIJ, 13(7) 2013 [270-283] Comprehensive screening of diuretics in human urine using liquid chromatography tandem mass spectrometry Shobha Ahi1, Alka Beotra1*, G.B.K.S.Prasad2 1National Dope Testing Laboratory, Ministry of Youth Affairs and Sports, CGO Complex, Lodhi Road, New Delhi,-110003, (INDIA) 2SOS in Biochemistry, Jiwaji University, Gwalior, (INDIA) E-mail : [email protected] ABSTRACT KEYWORDS Diuretics are drugs that increase the rate of urine flow and sodium excretion Doping, diuretics; to adjust the volume and composition of body fluids. There are several LC-MS/MS; WADA; major categories of this drug class and the compounds vary greatly in Drugs of abuse. structure, physicochemical properties, effects on urinary composition and renal haemodynamics, and site mechanism of action. Diuretics are often abused by athletes to excrete water for rapid weight loss and to mask the presence of other banned substances. Because of their abuse by athletes, ’s (WADA) diuretics have been included in the World Anti-Doping Agency list of prohibited substances. The diuretics are routinely screened by anti- doping laboratories as the use of diuretics is banned both in-competition and out-of-competition. This work provides an improved, fast and selective –tandem mass spectrometric (LC/MS/MS) method liquid chromatography for the screening of 22 diuretics and probenecid in human urine. The samples preparation was performed by liquid-liquid extraction. The limit of detection (LOD) for all substances was between 10-20 ng/ml or better.
  • New Prohibited Substances Addition to Procedures Using Triple Quadrupole LC/MS2 Technique

    New Prohibited Substances Addition to Procedures Using Triple Quadrupole LC/MS2 Technique

    Poster MANFRED DONIKE WORKSHOP Pop V, Bican G, Pop A, Lamor M, Zorio M New prohibited substances addition to procedures using triple quadrupole LC/MS2 technique Romanian Doping Control Laboratory, Bucharest, ROMANIA Abstract New substances are added each year to the different classes of substances of WADA’s Prohibited List and have to be included in the test menu of each accredited doping control laboratory. For the analysis of some of these compounds the technique of choice is the LC/MS2 technique. Furthermore, with the decrease of MRPL levels, for stimulants from 500 ng/mL to 100 ng/mL and for narcotics from 200 ng/mL to 50 ng/mL, beginning from the entering in force on 1 January 2013 of the new WADA Technical Document TD2013MRPL, some of the compounds analyzed by the current GC/MS based procedure for stimulants and narcotics needed to be transferred to the LC/MS2 based procedure in order to lower their limit of detection. This paper-work presents the optimal conditions for preparation, separation and identification of new substances introduced to the LC/MS2 technique based procedures during the year 2012. Introduction Liquid chromatography coupled with mass spectrometry is increasingly used in doping control laboratories [1]. The current work presents the optimization of the LC/MS2 detection parameters and the introduction of the prohibited substances in the existent procedures, depending on the characteristics of the studied compounds. The studied compounds are benzthiazide, cyclopenthiazide, cyclothiazide, epitizide, hydroflumethiazide and polythiazide (thiazide diuretic compounds), tramadol and its O-desmethyl metabolite (narcotic compound from the monitoring program [2]), cyclazodone, pentetrazole, prolintane, propylhexedrine and selegiline (stimulants transferred from the GC/MS- to the LC/MS2-based procedure due to the decreasing of the MRPL levels for stimulants and narcotics [3]).
  • Drugs and Life-Threatening Ventricular Arrhythmia Risk: Results from the DARE Study Cohort

    Drugs and Life-Threatening Ventricular Arrhythmia Risk: Results from the DARE Study Cohort

    Open Access Research BMJ Open: first published as 10.1136/bmjopen-2017-016627 on 16 October 2017. Downloaded from Drugs and life-threatening ventricular arrhythmia risk: results from the DARE study cohort Abigail L Coughtrie,1,2 Elijah R Behr,3,4 Deborah Layton,1,2 Vanessa Marshall,1 A John Camm,3,4,5 Saad A W Shakir1,2 To cite: Coughtrie AL, Behr ER, ABSTRACT Strengths and limitations of this study Layton D, et al. Drugs and Objectives To establish a unique sample of proarrhythmia life-threatening ventricular cases, determine the characteristics of cases and estimate ► The Drug-induced Arrhythmia Risk Evaluation study arrhythmia risk: results from the the contribution of individual drugs to the incidence of DARE study cohort. BMJ Open has allowed the development of a cohort of cases of proarrhythmia within these cases. 2017;7:e016627. doi:10.1136/ proarrhythmia. Setting Suspected proarrhythmia cases were referred bmjopen-2017-016627 ► These cases have provided crucial safety by cardiologists across England between 2003 and 2011. information, as well as underlying clinical and ► Prepublication history for Information on demography, symptoms, prior medical and genetic data. this paper is available online. drug histories and data from hospital notes were collected. ► Only patients who did not die as a result of the To view these files please visit Participants Two expert cardiologists reviewed data the journal online (http:// dx. doi. proarrhythmia could be included. for 293 referred cases: 130 were included. Inclusion org/ 10. 1136/ bmjopen- 2017- ► Referral of cases by cardiologists alone may have criteria were new onset or exacerbation of pre-existing 016627).
  • Diuretics in Clinical Practice. Part I: Mechanisms of Action, Pharmacological Effects and 1

    Diuretics in Clinical Practice. Part I: Mechanisms of Action, Pharmacological Effects and 1

    Review Diuretics in clinical practice. Part I: mechanisms of action, pharmacological effects and 1. Introduction clinical indications of diuretic 2. Principles of diuretic action and classification of diuretic compounds compounds † 3. Carbonic anhydrase inhibitors Pantelis A Sarafidis , Panagiotis I Georgianos & Anastasios N Lasaridis Aristotle University of Thessaloniki, AHEPA Hospital, Section of Nephrology and Hypertension, 4. Osmotic diuretics 1st Department of Medicine, Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece 5. Loop diuretics 6. Thiazides and thiazide-related Importance of the field: Diuretics are among the most important drugs of our diuretics therapeutic armamentarium and have been broadly used for > 50 years, 7. Potassium-retaining diuretics providing important help towards the treatment of several diseases. Although all diuretics act primarily by impairing sodium reabsorption in the renal 8. Conclusion tubules, they differ in their mechanism and site of action and, therefore, in 9. Expert opinion their specific pharmacological properties and clinical indications. Loop diure- tics are mainly used for oedematous disorders (i.e., cardiac failure, nephrotic syndrome) and for blood pressure and volume control in renal disease; thiazides and related agents are among the most prescribed drugs for hypertension treatment; aldosterone-blockers are traditionally used for primary or secondary aldosteronism; and other diuretic classes have more specific indications. Areas covered in this review: This article discusses the mechanisms of action, pharmacological effects and clinical indications of the various diuretic classes For personal use only. used in everyday clinical practice, with emphasis on recent knowledge sug- gesting beneficial effects of certain diuretics on clinical conditions distinct from the traditional indications of these drugs (i.e., heart protection for aldosterone blockers).
  • DIURETICS Diuretics Are Drugs That Promote the Output of Urine Excreted by the Kidneys

    DIURETICS Diuretics Are Drugs That Promote the Output of Urine Excreted by the Kidneys

    DIURETICS Diuretics are drugs that promote the output of urine excreted by the Kidneys. The primary action of most diuretics is the direct inhibition of Na+ transport at one or more of the four major anatomical sites along the nephron, where Na+ reabsorption takes place. The increased excretion of water and electrolytes by the kidneys is dependent on three different processes viz., glomerular filtration, tubular reabsorption (active and passive) and tubular secretion. Diuretics are very effective in the treatment of Cardiac oedema, specifically the one related with congestive heart failure. They are employed extensively in various types of disorders, for example, nephritic syndrome, diabetes insipidus, nutritional oedema, cirrhosis of the liver, hypertension, oedema of pregnancy and also to lower intraocular and cerebrospinal fluid pressure. Therapeutic Uses of Diuretics i) Congestive Heart Failure: The choice of the diuretic would depend on the severity of the disorder. In an emergency like acute pulmonary oedema, intravenous Furosemide or Sodium ethacrynate may be given. In less severe cases. Hydrochlorothiazide or Chlorthalidone may be used. Potassium-sparing diuretics like Spironolactone or Triamterene may be added to thiazide therapy. ii) Essential hypertension: The thiazides usually sever as primary antihypertensive agents. They may be used as sole agents in patients with mild hypertension or combined with other antihypertensives in more severe cases. iii) Hepatic cirrhosis: Potassium-sparing diuretics like Spironolactone may be employed. If Spironolactone alone fails, then a thiazide diuretic can be added cautiously. Furosemide or Ethacrymnic acid may have to be used if the oedema is regractory, together with spironolactone to lessen potassium loss. Serum potassium levels should be monitored periodically.
  • Extracts from PRAC Recommendations on Signals Adopted at the 9-12 March 2020 PRAC

    Extracts from PRAC Recommendations on Signals Adopted at the 9-12 March 2020 PRAC

    6 April 20201 EMA/PRAC/111218/2020 Corr2,3 Pharmacovigilance Risk Assessment Committee (PRAC) New product information wording – Extracts from PRAC recommendations on signals Adopted at the 9-12 March 2020 PRAC The product information wording in this document is extracted from the document entitled ‘PRAC recommendations on signals’ which contains the whole text of the PRAC recommendations for product information update, as well as some general guidance on the handling of signals. It can be found here (in English only). New text to be added to the product information is underlined. Current text to be deleted is struck through. 1. Immune check point inhibitors: atezolizumab; cemiplimab; durvalumab – Tuberculosis (EPITT no 19464) IMFINZI (durvalumab) Summary of product characteristics 4.4. Special warnings and precautions for use Immune-mediated pneumonitis [..] Patients with sSuspected pneumonitis should be evaluated confirmed with radiographic imaging and other infectious and disease-related aetiologies excluded, and managed as recommended in section 4.2. LIBTAYO (cemiplimab) Summary of product characteristics 1 Expected publication date. The actual publication date can be checked on the webpage dedicated to PRAC recommendations on safety signals. 2 A footnote was deleted on 8 April 2020 for the signal on thiazide and thiazide-like diuretics (see page 3). 3 A minor edit was implemented in the product information of the signal on thiazide and thiazide-like diuretics on 5 June 2020 (see page 4). Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 An agency of the European Union © European Medicines Agency, 2020.
  • Diuretic-Induced Hyponatraemia in Elderly Hypertensive Women

    Diuretic-Induced Hyponatraemia in Elderly Hypertensive Women

    Journal of Human Hypertension (2003) 17, 151 & 2003 Nature Publishing Group All rights reserved 0950-9240/03 $25.00 www.nature.com/jhh LETTER TO THE EDITOR Diuretic-induced hyponatraemia in elderly hypertensive women Journal of Human Hypertension there were 10 with plasma so- plasma sodium of 111 mmol/l (2003) 17, 151. doi:10.1038/ dium levels in the range 101– when inadvertently rechallenged sj.jhh.1001513 109 mmol/l. Of the 26, 11 had with thiazides, the agent this time plasma potassium levels less than being hydrochlorothiazide copre- My experience of diuretic- 3.5 mmol/l. The age range was scribed with amiloride. I now induced hyponatraemia in the 74–93 and 22 were women. Hy- utilise torasemide as an adjunc- elderly is in accordance with the drochlorothiazide was the offend- tive diuretic in patients with a observations made by the ing agent in 12 cases, having been previous history of thiazide- authors.1 In my personal series coprescribed with amiloride in induced hyponatraemia. The data of 61 cases of severe hyponatraemia 10 instances, and with triamterene presented here extend the obser- (plasma sodium o120 mmol/l), in two. Bendrofluazide was the vations I published previously on compiled over a period of 18 offending agent in nine instances, this topic. years in patients aged 465, 26 the dose being 2.5 mg/day in were attributable to thiazide seven instances (coprescribed diuretics, culprit drugs in seven with amiloride in one instance), References other cases being frusemide (three and 5.0 mg/day in the other two. 1 Sharabi Y et al.
  • Ehealth DSI [Ehdsi V2.2.2-OR] Ehealth DSI – Master Value Set

    Ehealth DSI [Ehdsi V2.2.2-OR] Ehealth DSI – Master Value Set

    MTC eHealth DSI [eHDSI v2.2.2-OR] eHealth DSI – Master Value Set Catalogue Responsible : eHDSI Solution Provider PublishDate : Wed Nov 08 16:16:10 CET 2017 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 1 of 490 MTC Table of Contents epSOSActiveIngredient 4 epSOSAdministrativeGender 148 epSOSAdverseEventType 149 epSOSAllergenNoDrugs 150 epSOSBloodGroup 155 epSOSBloodPressure 156 epSOSCodeNoMedication 157 epSOSCodeProb 158 epSOSConfidentiality 159 epSOSCountry 160 epSOSDisplayLabel 167 epSOSDocumentCode 170 epSOSDoseForm 171 epSOSHealthcareProfessionalRoles 184 epSOSIllnessesandDisorders 186 epSOSLanguage 448 epSOSMedicalDevices 458 epSOSNullFavor 461 epSOSPackage 462 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 2 of 490 MTC epSOSPersonalRelationship 464 epSOSPregnancyInformation 466 epSOSProcedures 467 epSOSReactionAllergy 470 epSOSResolutionOutcome 472 epSOSRoleClass 473 epSOSRouteofAdministration 474 epSOSSections 477 epSOSSeverity 478 epSOSSocialHistory 479 epSOSStatusCode 480 epSOSSubstitutionCode 481 epSOSTelecomAddress 482 epSOSTimingEvent 483 epSOSUnits 484 epSOSUnknownInformation 487 epSOSVaccine 488 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 3 of 490 MTC epSOSActiveIngredient epSOSActiveIngredient Value Set ID 1.3.6.1.4.1.12559.11.10.1.3.1.42.24 TRANSLATIONS Code System ID Code System Version Concept Code Description (FSN) 2.16.840.1.113883.6.73 2017-01 A ALIMENTARY TRACT AND METABOLISM 2.16.840.1.113883.6.73 2017-01
  • (12) Patent Application Publication (10) Pub. No.: US 2005/0113314 A1 Fong Et Al

    (12) Patent Application Publication (10) Pub. No.: US 2005/0113314 A1 Fong Et Al

    US 20050113314A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2005/0113314 A1 Fong et al. (43) Pub. Date: May 26, 2005 (54) CICLETANINE IN COMBINATION WITH Publication Classification ORAL ANTIDIABETIC AND/OR BLOOD LIPID-LOWERING AGENTS ASA COMBINATION THERAPY FOR DIABETES (51) Int. Cl." ..................... A61K 31/70; A61K 31/4741; AND METABOLIC SYNDROME A61K 31/426; A61K 31/155; A61K 31/175 (76) Inventors: Benson M. Fong, San Francisco, CA (52) U.S. Cl. ............................ 514/25; 514/302; 514/369; (US); Glenn V. Cornett, Palo Alto, CA 514/592; 514/635 (US) Correspondence Address: KNOBBE MARTENS OLSON & BEAR LLP 2040 MAIN STREET (57) ABSTRACT FOURTEENTH FLOOR IRVINE, CA 92614 (US) Preferred embodiments of the present invention are related to novel therapeutic drug combinations and methods for (21) Appl. No.: 10/929,108 treating and/or preventing complications in patients with (22) Filed: Aug. 27, 2004 diabetes and/or metabolic Syndrome. More particularly, aspects of the present invention are related to using a Related U.S. Application Data combination of cicletanine and an oral antidiabetic agent for treating and/or preventing complications (including microal (60) Provisional application No. 60/498,916, filed on Aug. buminuria, nephropathies, retinopathies and other compli 29, 2003. cations) in patients with diabetes or metabolic Syndrome. US 2005/0113314 A1 May 26, 2005 CICLETANNE IN COMBINATION WITH ORAL women >0.85) and/or Body Mass Index >30 kg/M); 6) ANTIDIABETIC AND/OR BLOOD micro albuminuria (urine albumin excretion: 220 ugmin' LIPID-LOWERING AGENTS ASA COMBINATION or albumin/creatinine ratio22.0 mg/mmol.
  • Heart Failure — Managing Newly Diagnosed and Decompensated

    Heart Failure — Managing Newly Diagnosed and Decompensated

    Clinical Guideline Heart failure: Managing newly diagnosed and decompensated patients admitted to hospital 1. Confirmation of Diagnosis Person with signs and symptoms suggesting heart failure Detailed history and clinical examination Consider aetiology for new diagnosis of heart Suspected diagnosis Confirmed failure or underlying cause for exacerbation of of heart failure diagnosis of heart chronic heart failure and exclude treatable Diagnosis has not failure causes. been confirmed by Diagnosis confirmed Arrange other investigations: echocardiogram by previous . CXR echocardiogram . ECG . FBC . U&Es and Creatinine . LFTs . TFTs . RBG . Cholesterol If current echocardiogram not Diagnosis confirmed by clinically relevant, echocardiogram, if possible Heart failure excluded so request repeat performed as an in-patient review diagnosis echo, if possible and adhering to Advancing performed as an in- Quality heart failure (AQHF) patient indicators Heart failure with preserved ejection Heart failure due to significant left ventricular fraction / diastolic dysfunction (EF systolic dysfunction (EF < 40%) >55%) • Update primary diagnosis on PCIS / -Update primary diagnosis on PCIS Cerner and document in casenotes /Cerner and document in casenotes. Proceed to Management of Confirmed Heart Failure Heart failure — managing newly diagnosed and decompensated patients in acute care — clinical guidelines, v1 Principal author: Dr P Saravanan Approved by Medicines Clinical Guideline Team: July 2013 Review by: July 2016 Page 1 of 27 2. Inpatient management Heart failure with preserved Heart failure due to left ventricular ejection fraction systolic dysfunction (EF < 40%) • Referral to heart failure specialist team. • Arrange admission to appropriate ward/unit Refer to Heart Failure Fluid balance: Drug management: Specialist Nurse for 1. Fluid restriction 1-2 litres in 24 1.