Annexes to the EMA Annual Report 2009
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London, 29 May 2009 Doc.Ref
European Medicines Agency Pre-Authorisation Evaluation of Medicines for Human Use London, 29 May 2009 Doc.Ref. EMEA/CHMP/282149/2009 COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE SUMMARY OF POSITIVE OPINION* for VEDROP International Nonproprietary Name (INN): tocofersolan On 29 May 2009 the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending to grant a marketing authorisation under exceptional circumstances for the medicinal product Vedrop, 50 mg/ml, oral solution indicated in vitamin E deficiency due to digestive malabsorption in paediatric patients suffering from congenital chronic cholestasis or hereditary chronic cholestasis. The applicant for this medicinal product is Orphan Europe S.A.R.L. The active substance of Vedrop is tocofersolan, an alimentary tract and metabolism medicinal product (ATC code A11 HA08, other plain vitamin preparations). Tocofersolan, is vitamin E that has been made water-soluble by attaching it to polyethylene glycol 1000, and thereby can be absorbed from the gut in patients who have difficulty absorbing fats and vitamin E from the diet due congenital chronic or hereditary chronic cholestasis. The use of vitamin E preparations in this population helps to prevent neurological deterioration due to vitamin E deficiency. The benefits with Vedrop are improvement or stabilisation of neurological abnormalities due to vitamin E deficiency in patients with congenital chronic or hereditary chronic cholestasis. The most common side effect is diarrhoea. A pharmacovigilance plan for Vedrop, as for all medicinal products, will be implemented as part of the marketing authorisation. The approved indication is: “Vedrop is indicated in vitamin E deficiency due to digestive malabsorption in paediatric patients suffering from congenital chronic cholestasis or hereditary chronic cholestasis, from birth (in term newborns) to 16 or 18 years of age, depending on the region”. -
Unique Binding Behavior of the Recently Approved Angiotensin II Receptor Blocker Azilsartan Compared with That of Candesartan
Hypertension Research (2013) 36, 134–139 & 2013 The Japanese Society of Hypertension All rights reserved 0916-9636/13 www.nature.com/hr ORIGINAL ARTICLE Unique binding behavior of the recently approved angiotensin II receptor blocker azilsartan compared with that of candesartan Shin-ichiro Miura1,2,3, Atsutoshi Okabe4, Yoshino Matsuo1, Sadashiva S Karnik3 and Keijiro Saku1,2 The angiotensin II type 1 (AT1) receptor blocker (ARB) candesartan strongly reduces blood pressure (BP) in patients with hypertension and has been shown to have cardioprotective effects. A new ARB, azilsartan, was recently approved and has been shown to provide a more potent 24-h sustained antihypertensive effect than candesartan. However, the molecular interactions of azilsartan with the AT1 receptor that could explain its strong BP-lowering activity are not yet clear. To address this issue, we examined the binding affinities of ARBs for the AT1 receptor and their inverse agonist activity toward the production of inositol phosphate (IP), and we constructed docking models for the interactions between ARBs and the receptor. Azilsartan, unlike candesartan, has a unique moiety, a 5-oxo-1,2,4-oxadiazole, in place of a tetrazole ring. Although the results regarding the binding affinities of azilsartan and candesartan demonstrated that these ARBs interact with the same sites in the AT1 receptor (Tyr113,Lys199 and Gln257), the hydrogen bonding between the oxadiazole of azilsartan-Gln257 is stronger than that between the tetrazole of candesartan-Gln257, according to molecular docking models. An examination of the inhibition of IP production by ARBs using constitutively active mutant receptors indicated that inverse agonist activity required azilsartan– Gln257 interaction and that azilsartan had a stronger interaction with Gln257 than candesartan. -
Edarbi Generic Name: Azilsartan Manufacturer1
Brand Name: Edarbi Generic Name: azilsartan Manufacturer1: Takeda Pharmaceutical Company Drug Class1,2,3,4,5: Anti‐hypertensive, Angiotensin II receptor blocker Uses: Labeled Uses1,2,3,4,5: Hypertension, alone or as adjunctive therapy with other antihypertensives Unlabeled Uses: 1,2,3,4,5 Mechanism of Action : Azilsartan inhibits the binding of angiotensin II to AT1 receptor. This blocks the vasoconstrictor and aldosterone‐secreting effects of angiotensin II. Pharmacokinetics1,2,3,4,5: Absorption: Tmax 1.5‐3 hours Vd 16 L t1/2 11 hours Clearance 2.3 mL/min Protein binding >99% Bioavailability 60% Metabolism: Azilsartan is metabolized via O‐dealkylation and decarboxylation into two primary metabolites. CYP2C9 is the major enzyme responsible for azilsartan metabolism. Elimination: Azilsartan is eliminated through the feces (55%) and the urine (42%). Only 15% is eliminated as the unchanged drug. Efficacy: Bakris GL, Sica D, Weber M, White WB, Roberts A, Perez A, Cao C, et al. The comparative effects of azilsartan medoxomil and olmesartan on ambulatory and clinic blood pressure. Journal of Clinical Hypertension. 2001;13(2):81‐88. Study Design: Randomized, double‐blind, multicenter, parallel group, placebo‐controlled study design Description of Study: Methods: One thousand two hundred seventy‐five patients meeting the criteria of primary hypertension were randomized to receive either placebo, 40mg of olmesartan, or 20mg, 40mg, or 80mg of azilsartan for six weeks. The primary end point, change in 24 hour mean systolic blood pressure at week six, was assessed by ambulatory blood pressure monitoring performed at baseline and the final visit. The key secondary endpoint was change in trough sitting clinic systolic blood pressure at week six. -
Efficacy and Safety of Azilsartan Medoxomil, an Angiotensin Receptor
Juhasz et al. Clinical Hypertension (2018) 24:2 DOI 10.1186/s40885-018-0086-4 RESEARCH Open Access Efficacy and safety of azilsartan medoxomil, an angiotensin receptor blocker, in Korean patients with essential hypertension Attila Juhasz1,5, Jingtao Wu2, Michie Hisada2, Tomoka Tsukada3,6 and Myung Ho Jeong4* Abstract Background: This was a phase 3, randomized, double-blind, placebo-controlled study. Methods: Adult Korean patients with essential hypertension and a baseline mean sitting clinic systolic blood pressure (scSBP) ≥150 and ≤180 mmHg were randomized to 6-week treatment with placebo (n = 65), azilsartan medoxomil (AZL-M) 40 mg (n = 132), or AZL-M 80 mg (n = 131). The primary endpoint was the change from baseline to week 6 in trough scSBP. Results: The least-squares mean (standard error) change from baseline in trough scSBP in the placebo, AZL-M 40-mg, and 80-mg groups at week 6 were − 8.8 (2.00), − 22.1 (1.41), and − 23.7 (1.40) mmHg, respectively (p < 0.001 for AZL-M 40 and 80 mg vs placebo). No clinically meaningful heterogeneity in efficacy was observed between subgroups (age, sex, diabetes status) and the overall population. Treatments were well tolerated and adverse events were similar between groups. Conclusions: Results of this study confirm a positive benefit-risk profile of AZL-M for essential hypertension in Korean adults. Trial registration: Clinicaltrial.gov; identifier number: NCT02203916. Registered July 28, 2014 (retrospectively registered) Keywords: Hypertension, Azilsartan medoxomil, Angiotensin II receptor antagonist, Blood pressure, Korea Background cerebrovascular and cardiovascular disease, which are now Hypertension is a leading cause of preventable death in the second and third most common causes of death in developed nations and of increasing prevalence in develop- Korea, respectively [11]. -
Azilsartan, but Not Candesartan Improves Left Ventricular Diastolic Function in Patients with Hypertension and Heart Failure*
International Journal of Gerontology 9 (2015) 201e205 Contents lists available at ScienceDirect International Journal of Gerontology journal homepage: www.ijge-online.com Original Article Azilsartan, but not Candesartan Improves Left Ventricular Diastolic Function in Patients with Hypertension and Heart Failure* Mari Sakamoto 1, Masanori Asakura 1, 2, Atsushi Nakano 2, Hideaki Kanzaki 1, Yasuo Sugano 1, Makoto Amaki 1, Takahiro Ohara 1, Takuya Hasegawa 1, * Toshihisa Anzai 1, Masafumi Kitakaze 1, 2 1 Department of Cardiovascular Medicine, 2 Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center, Suita, Japan article info summary Article history: Background: Diastolic dysfunction is a major cause of heart failure (HF) with a preserved ejection fraction Received 1 June 2015 (HFpEF); however, there is no clear strategy for treating diastolic dysfunction. Myocardial and vascular Received in revised form abnormalities may cause HFpEF, which indicates that correcting both abnormalities may specifically 4 June 2015 improve the severity of diastolic dysfunction. Candesartan primarily affects the myocardium, but Accepted 8 June 2015 azilsartan affects the myocardium and the aortic vasculature. This study was undertaken to test the Available online 14 December 2015 hypothesis that azilsartan, but not candesartan, improves left ventricular (LV) diastolic dysfunction in patients with hypertension and HFpEF. Keywords: angiotensin receptor blocker, Methods: Among patients with HF in our database, the patients who received azilsartan or candesartan fi brain natriuretic peptide, were retrospectively screened. Fifteen patients treated with azilsartan were identi ed, and sex-matched diastolic dysfunction, patients who received candesartan were blindly selected. echocardiography, Results: At baseline, there were no significant differences between the two groups in clinical findings, heart failure echocardiographic parameters, and plasma brain natriuretic peptide levels. -
Myocardial Metabolism in Heart Failure: Purinergic Signalling and Other
Accepted Manuscript Myocardial metbolism in heart failure: Purinergic signalling and other metabolic concepts Andreas L. Birkenfeld, Jens Jordan, Markus Dworak, Tobias Merkel, Geoffrey Burnstock PII: S0163-7258(18)30153-0 DOI: doi:10.1016/j.pharmthera.2018.08.015 Reference: JPT 7270 To appear in: Pharmacology and Therapeutics Please cite this article as: Andreas L. Birkenfeld, Jens Jordan, Markus Dworak, Tobias Merkel, Geoffrey Burnstock , Myocardial metbolism in heart failure: Purinergic signalling and other metabolic concepts. Jpt (2018), doi:10.1016/j.pharmthera.2018.08.015 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ACCEPTED MANUSCRIPT Myocardial metbolism in heart failure: Purinergic signalling and other metabolic concepts Andreas L. Birkenfeld MD1,2,3,4, Jens Jordan MD5, Markus Dworak PhD6, Tobias Merkel PhD6 and Geoffrey Burnstock PhD7,8. Affiliations 1Medical Clinic III, Universitätsklinikum "Carl Gustav Carus", Technische Universität Dresden, Dresden, Germany 2Paul Langerhans Institute Dresden of the Helmholtz Center Munich at University Hospital and Faculty of Medicine, Dresden, German Center for Diabetes Research -
Estonian Statistics on Medicines 2016 1/41
Estonian Statistics on Medicines 2016 ATC code ATC group / Active substance (rout of admin.) Quantity sold Unit DDD Unit DDD/1000/ day A ALIMENTARY TRACT AND METABOLISM 167,8985 A01 STOMATOLOGICAL PREPARATIONS 0,0738 A01A STOMATOLOGICAL PREPARATIONS 0,0738 A01AB Antiinfectives and antiseptics for local oral treatment 0,0738 A01AB09 Miconazole (O) 7088 g 0,2 g 0,0738 A01AB12 Hexetidine (O) 1951200 ml A01AB81 Neomycin+ Benzocaine (dental) 30200 pieces A01AB82 Demeclocycline+ Triamcinolone (dental) 680 g A01AC Corticosteroids for local oral treatment A01AC81 Dexamethasone+ Thymol (dental) 3094 ml A01AD Other agents for local oral treatment A01AD80 Lidocaine+ Cetylpyridinium chloride (gingival) 227150 g A01AD81 Lidocaine+ Cetrimide (O) 30900 g A01AD82 Choline salicylate (O) 864720 pieces A01AD83 Lidocaine+ Chamomille extract (O) 370080 g A01AD90 Lidocaine+ Paraformaldehyde (dental) 405 g A02 DRUGS FOR ACID RELATED DISORDERS 47,1312 A02A ANTACIDS 1,0133 Combinations and complexes of aluminium, calcium and A02AD 1,0133 magnesium compounds A02AD81 Aluminium hydroxide+ Magnesium hydroxide (O) 811120 pieces 10 pieces 0,1689 A02AD81 Aluminium hydroxide+ Magnesium hydroxide (O) 3101974 ml 50 ml 0,1292 A02AD83 Calcium carbonate+ Magnesium carbonate (O) 3434232 pieces 10 pieces 0,7152 DRUGS FOR PEPTIC ULCER AND GASTRO- A02B 46,1179 OESOPHAGEAL REFLUX DISEASE (GORD) A02BA H2-receptor antagonists 2,3855 A02BA02 Ranitidine (O) 340327,5 g 0,3 g 2,3624 A02BA02 Ranitidine (P) 3318,25 g 0,3 g 0,0230 A02BC Proton pump inhibitors 43,7324 A02BC01 Omeprazole -
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 . -
Adenosine A1 Receptor Antagonists in Clinical Research and Development Berthold Hocher1,2
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector mini review http://www.kidney-international.org & 2010 International Society of Nephrology Adenosine A1 receptor antagonists in clinical research and development Berthold Hocher1,2 1Institute of Nutritional Science, University of Potsdam, Potsdam, Germany and 2Center for Cardiovascular Research/Department of Pharmacology and Toxicology, Charite´, Campus Mitte, Berlin, Germany Selective adenosine A1 receptor antagonists targeting renal Various lines of evidence implicate impaired renal function as microcirculation are novel pharmacologic agents that are a risk factor in patients with congestive heart failure (CHF). currently under development for the treatment of acute Conventional diuretics may aggravate renal dysfunction and heart failure as well as for chronic heart failure. Despite can result in neurohumoral activation and activation of the several studies showing improvement of renal function TGF mechanism in the kidney.1 Impaired kidney function and/or increased diuresis with adenosine A1 antagonists, might not just be a risk factor, but is also currently observed particularly in chronic heart failure, these findings were as having a role—and thus potentially as target—in disease not confirmed in a large phase III trial in acute heart failure progression of heart failure patients.1 Evolving new ther- patients. However, lessons can be learned from these and apeutic strategies that enhance renal function include other studies, and there might still be a potential role for administration of B-type natriuretic peptide, adenosine the clinical use of adenosine A1 antagonists. and vasopressin antagonists, and ultrafiltration methods. We review the role of adenosine A1 receptors in the Prospective studies are needed to evaluate whether these new regulation of renal function, and emerging data regarding renal-enhancing strategies will improve patient outcome in the safety and efficacy of A1 adenosine receptor antagonists CHF. -
Illinois College Jacksonville, Illinois
TRANSACTIONS OF THE ILLINOIS STATE ACADEMY OF SCIENCE Supplement to Volume 106 105th Annual Meeting April 5-6, 2013 Illinois College Jacksonville, Illinois Illinois State Academy of Science Founded 1907 Affiliated with the Illinois State Museum, Springfield, Illinois TABLE OF CONTENTS Schedule of Events 3 Presentation Schedules At-a-Glance 4 ORAL AND POSTER PRESENTATION SESSIONS Oral Presentation Sessions: Title and Author Listings Session 1: Physics, Mathematics, & Astronomy 5 Session 2: Botany 5 Session 3: Cell, Molecular, & Developmental Biology 7 Session 4: Chemistry & Computer Science 8 Session 5: Environmental Science/Zoology 9 Session 6: Health Sciences, Microbiology, and STEM Education 10 Session 7: Zoology 11 Poster Presentation Sessions: Title and Author Listings Agriculture 13 Botany 13 Cell, Molecular, & Developmental Biology 15 Chemistry 16 Computer Science 17 Earth Science 18 Environmental Science 18 Health Sciences 19 Microbiology 19 Physics, Mathematics, & Astronomy 20 Zoology 21 1 ORAL AND POSTER PRESENTATION ABSTRACTS Oral Presentation Abstracts Session 1: Physics, Mathematics, & Astronomy 24 Session 2: Botany 25 Session 3: Cell, Molecular, & Developmental Biology 30 Session 4: Chemistry & Computer Science 35 Session 5: Environmental Science/Zoology 38 Session 6: Health Sciences, Microbiology, and STEM 42 Session 7: Zoology 45 Poster Presentation Abstracts Agriculture 50 Botany 50 Cell, Molecular, & Developmental Biology 59 Chemistry 66 Computer Science 70 Earth Science 71 Environmental Science 72 Health Sciences 74 Microbiology -
Heart Failure Guidelines
; ; ; † § ** ; ; † † * ; ; † † ; ; ¶ † ; * † * ; . 2013;128:e240–e327. † ; DOI: 10.1161/CIR.0b013e31829e8776 †‡ Circulation * †† * ; Tamara Horwich, MD, FACC Tamara ; ‖ ; Barbara Riegel, DNSc, RN, FAHA ; Barbara Riegel, ; Patrick E. McBride, MD, MPH, FACC ; Patrick † ; Wayne C. Levy, MD, FACC C. Levy, Wayne ; # † † ; Emily J. Tsai, MD, FACC ; Emily J. ; Biykem Bozkurt, MD, PhD, FACC, FAHA Bozkurt, MD, PhD, FACC, ; Biykem ; Gregg C. Fonarow, MD, FACC, FAHA MD, FACC, C. Fonarow, ; Gregg † † † * * * e240 ; Lynne W. Stevenson, MD, FACC Stevenson, W. ; Lynne ; Judith E. Mitchell, MD, FACC, FAHA ; Judith E. Mitchell, MD, FACC, † † ; Maryl R. Johnson, MD, FACC, FAHA ; Maryl R. Johnson, MD, FACC, * † * ; Donald E. Casey, Jr, MD, MPH, MBA, FACP, FAHA FACP, MD, MPH, MBA, Jr, ; Donald E. Casey, † * WRITING COMMITTEE MEMBERS Bruce L. Wilkoff, MD, FACC, FHRS MD, FACC, Wilkoff, Bruce L. Journal of the American College of Cardiology. American College of the Journal Management of Heart Failure Clyde W. Yancy, MD, MSc, FACC, FAHA, Chair FAHA, MD, MSc, FACC, Yancy, W. Clyde ACCF/AHA Practice Guideline ACCF/AHA International Society for Heart and Lung Transplantation International Society for Heart and Lung 2013 ACCF/AHA Guideline for the Guideline for ACCF/AHA 2013 W.H. Wilson Tang, MD, FACC Tang, Wilson W.H. Flora Sam, MD, FACC, FAHA Flora Sam, MD, FACC, Heart Association Task Force on Practice Guidelines Force Task Association Heart Edward K. Kasper, MD, FACC, FAHA MD, FACC, K. Kasper, Edward James L. Januzzi, MD, FACC John J.V. McMurray, MD, FACC McMurray, John J.V. Stephen A. Geraci, MD, FACC, FAHA, FCCP FAHA, A. Geraci, MD, FACC, Stephen . 2013;128:e240-e327.) is available at http://circ.ahajournals.org is available Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation Association of Cardiovascular American by the Endorsed Pamela N. -
WO 2011/089216 Al
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date t 28 July 2011 (28.07.2011) WO 2011/089216 Al (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 47/48 (2006.01) C07K 1/13 (2006.01) kind of national protection available): AE, AG, AL, AM, C07K 1/1 07 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, (21) Number: International Application DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/EP201 1/050821 HN, HR, HU, ID, J , IN, IS, JP, KE, KG, KM, KN, KP, (22) International Filing Date: KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, 2 1 January 201 1 (21 .01 .201 1) ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, (25) Filing Language: English SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, (26) Publication Language: English TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 1015 1465. 1 22 January 2010 (22.01 .2010) EP kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, (71) Applicant (for all designated States except US): AS- ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, CENDIS PHARMA AS [DK/DK]; Tuborg Boulevard TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, 12, DK-2900 Hellerup (DK).