DOCSLIB.ORG

Efficacy of Bezlotoxumab, the Monoclonal Antibody Targeting C. Difficile Toxin B, for Prevention of C. Difficile Infection

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Efficacy of Bezlotoxumab, the Monoclonal Antibody Targeting C. Difficile Toxin B, for Prevention of C. Difficile Infection EP0176 European Congress of Clinical Microbiology and Efficacy of Bezlotoxumab, the Monoclonal Antibody Gerding DN1; Kelly CP2; Rahav G3; Lee C4; Dubberke E5; Infectious Diseases Kumar P6; Eves K7; Pedley A7; Tipping R7; Guris D7; Kartsonis N7; Dorr MB7 (ECCMID) 2016 Targeting C. difficile Toxin B, for Prevention of RAI Amsterdam, 1Hines VA Hospital, Hines, IL, USA; 2BIDMC & Harvard Medical School, Boston, MA, USA; Amsterdam, C. difficile Infection (CDI) Recurrence in Patients at High 3Sheba Medical Center, Tel Hashomer, Israel; 4St. Joseph’s Healthcare, Hamilton, ON, Canada; The Netherlands 5Washington University School of Medicine, St Louis, MO, USA; 6Georgetown University School of Medicine, April 09–12, 2016 Risk of Recurrence or CDI-Related Adverse Outcomes Washington, DC, USA; 7Merck & Co., Inc., Kenilworth, NJ, USA Outcome Measures Figure 2. CDI recurrence rates (A) and difference between bezlotoxumab and • The 95% Cl for the difference in recurrence rates between bezlotoxumab and Introduction and Purpose • CDI recurrence: A new episode of diarrhea associated with a positive stool test placebo (B) for subjects in high-risk groups placebo excluded zero for all high-risk groups except subjects infected with the 027 ribotype and subjects infected with any strain associated with poor outcomes for toxigenic C. difficile after clinical cure of baseline episode and within 12 weeks A) • It has been estimated that Clostridium difficile causes 172,000 infections each following study medication infusion Bezlotoxumab Placebo (027, 078, or 244 ribotypes) year across the 27 countries of the European Union among individuals 2 years 45 42% • Among subjects with 1 risk factors, recurrent CDI occurred in 17% (100/588) of of age1,2 However, these data do not take into account a recently documented • Global cure: Clinical cure of initial episode and no recurrent CDI within 12 weeks 41% 40 bezlotoxumab recipients and 30% (174/582) of placebo recipients 70% increase in incidence of C. difficile infection (CDI) and considerable potential following study infusion t 35 34% 3 32% Global Cure for missed diagnoses across Europe Data Analysis 31% 30 29% 28% 27% • Across the two trials, treatment with bezlotoxumab conferred a 9.7% increase in • Although antibiotic treatment of primary CDI is often successful, up to 35% of • Endpoints were estimated from the pooled MODIFY dataset for subjects in the 25% 25 24% patients experience CDI recurrence after completing initial antibiotic therapy.4,5 bezlotoxumab and placebo groups who had the following risk factors for CDI 22% 22% incidence of global cure versus placebo (P 0.0001) 20 After first recurrence, patients have a 45% probability of a second recurrence, recurrence: age 65 years, 1 CDI episodes in the past 6 months, 2 previous 17% • Global cure rates for bezlotoxumab were consistently higher than placebo across 15% 15% with the risk increasing with further recurrences6 CDI episodes, immunocompromised, severe CDI (Zar 2), or infected with a 15 all high-risk groups (Figure 3) 11% strain associated with poor outcomes (027, 078, or 244 ribotype) % subjects, full analysis se 10 • Risk factors for CDI recurrence or CDI-related adverse outcomes include: age • The largest increases in global cure were in subjects 65 years of age (16.2%) 65 years,3,7 history of CDI,4,5 compromised immunity,8,9 clinically severe CDI • 95% confidence intervals (CIs) for the difference between treatment groups were 5 and those who were immunocompromised at study entry (15.3%) n= 390 405 216 219 100 126 169 145 122 125 102 115 89 100 781 773 (Zar score 2),10 and infection with a strain associated with poor outcomes calculated using Miettinen and Nurminen’s method 0 Age у65 у1 CDI у2 previous Immuno- Severe 027, 078, 027 strain Overall 7,11-13 14 15,16 Safety Outcomes (027, 078, or 244 ) episodes in past CDI compromized CDI (Zar or 244 strain 6 months episodes score у2) • Bezlotoxumab was generally well tolerated. The types and incidence of • MODIFY I and MODIFY II were global, randomized, double-blind, placebo-controlled B) adverse events (AEs) and serious AEs were similar across the bezlotoxumab trials of the efficacy and safety of bezlotoxumab (a human monoclonal antibody Results Bezlotoxumab Placebo Difference, %Absolute difference and placebo groups against C. difficile toxin B) alone and in combination with actoxumab (a human % (n/N) % (n/N) Absolute Relative % (95% CI) monoclonal antibody against C. difficile toxin A), for the prevention of CDI Study Population All subjects 16.5 (129/781) 26.6 (206/773) -10.1 -38.0 • AEs were generally as expected considering the underlying disease severity, Age у65 15.4 (60/390) 31.4 (127/405) -16.0 -50.9 baseline co-morbidities, and age of the population studied recurrence in adults receiving antibiotic treatment (standard of care [SOC]) • A total of 1554 subjects were included in the full analysis set for the pooled for primary or recurrent CDI17 analysis. Baseline demographics and characteristics were similar in the у1 CDI episodes in past 6 months 25.0 (54/216) 41.1 (90/219) -16.1 -39.2 – In both studies, bezlotoxumab substantially reduced CDI recurrence and had a bezlotoxumab (n= 781) and placebo (n= 773) pooled analysis groups (Table 1). у2 previous CDI episodes 29.0 (29/100) 42.1 (53/126) -13.1 -31.1 safety profile similar to placebo. The actoxumab arm of MODIFY I was dropped Immunocompromized 15.4 (26/169) 28.3 (41/145) -12.9 -45.6 Conclusions • The majority of subjects (76%) had at least one risk factor for CDI recurrence or from further study following interim analysis due to lack of efficacy and higher Severe CDI (Zar score у2) 10.7 (13/122) 22.4 (28/125) -11.7 -52.4 CDI-related adverse outcomes rate of serious adverse events and deaths compared with placebo 027, 078, or 244 strain 21.6 (22/102) 32.3 (37/115) -10.6 -33.0 • Bezlotoxumab, a monoclonal antibody targeting C. difficile toxin B, was efficacious in reducing CDI recurrence rates through 12 weeks when – Results for the combination of actoxumab and bezlotoxumab were similar to Table 1. Subject baseline characteristics 027 strain 23.6 (21/89) 34.0 (34/100) -10.4 -30.6 17 given to adults receiving SOC antibiotics for CDI (MODIFY I and II) bezlotoxumab alone. Thus, the addition of actoxumab did not improve efficacy. Bezlotoxumab Placebo -30 -20 -10 0 Therefore, only the bezlotoxumab alone versus placebo data are presented here (N=781) (N=773) • This pooled analysis showed that in key subpopulations at high risk for CDI recurrence and/or CDI-related adverse outcomes, bezlotoxumab Favors bezlotoxumab Favors placebo Number of subjects (%) CDI = C. difficile infection; CI = confidence interval. reduced CDI recurrence and increased rates of global cure compared Objective Subject characteristics with placebo Inpatient 530 (67.9) 520 (67.3) Figure 3. Global cure rates (A) and difference between bezlotoxumab and • To assess the efficacy of bezlotoxumab in subjects at increased risk for CDI Female 442 (56.6) 449 (58.1) placebo (B) for subjects in high-risk groups References recurrence or CDI-related adverse outcomes using pooled data from the MODIFY 65 years of age 390 (49.9) 405 (52.4) A) 1. Barbut F, et al. Clostridium Difficile infection in Europe: a CDI Europe report. 2013. http://www.multivu.com/assets/60637/ I and MODIFY II studies 1 CDI episodes in past 6 months 216 (27.7) 219 (28.3) Bezlotoxumab Placebo documents/60637-CDI-HCP-Report-original.pdf. 2. Bauer MP, et al. Lancet. 2011;377(9759):63–73. 70 66% 2 previous CDI episodes 100 (12.8) 126 (16.3) 64% 64% 3. Davies KA, et al. Lancet Infect Dis. 2014;14(12):1208-1219. 4. Aslam S, et al. Lancet Infect Dis. 2005;5(9):549–557. Severe CDI (Zar score 2) 122 (15.6) 125 (16.2) 60 57% 56% 54% 55% 54% Methods 52% 5. Kelly CP, LaMont JT. N Engl J Med. 2008;359(18):1932–1940. a 50% 49% Immunocompromized 169 (21.6) 145 (18.8) 50 48% 6. Sheitoyan-Pesant C, et al. Clin Infect Dis. 2016;62(5):574-580. 46% 45% b 42% PCR ribotype (N=490) (N=486) 40% 7. Lessa FC, et al. N Engl J Med. 2015;372(9):825–834. MODIFY I (MK-3415A-001, NCT01241552) and II (MK-3415A-002, NCT01513239) 40 • 8. Morrison M, et al. Clin Infect Dis. 2011;53(12):1173–1178. Most common strainsc 210 (42.9) 233 (47.9) were randomized, double-blind, placebo-controlled, multicenter, Phase 3 trials 9. See I, et al. Clin Infect Dis. 2014;58(10):1394–1400. 30 conducted from 01-Nov-2011 through 22-May-2015 at 322 sites in 30 countries. 027, 078, or 244 strain 102 (20.8) 115 (23.7) 10. Zar FA, et al. Clin Infect Dis. 2007;45(3):302–307. 20 11. Abou Chakra CN, et al. PLoS One. 2012;7(1):e30258. 027 strain 89 (18.2) 100 (20.6) • The design of both studies is summarized in Figure 1 % subjects, full analysis set 12. Inns T, et al. J Hosp Infect. 2013;84(3):235–241. a 10 Figure 1. Trial design flow diagram Defined on the basis of a subject’s medical history or use of immunosuppressive therapy. 13. Rao K, et al. Clin Infect Dis. 2015;61(2):233–241. bDenominator is subjects in the full analysis population with a positive culture. n= 251 195 117 92 100 126 111 73 69 61 102 115 50 45 781 773 14. Walker AS, et al. Clin Infect Dis. 2013;56(11):1589–1600. cMost common strains: ribotypes 027, 014, 002, 001, 106, or 020.
Load more

Recommended publications
  • Where Do Novel Drugs of 2016 Fit In?
    FORMULARY JEOPARDY: WHERE DO NOVEL DRUGS OF 2016 FIT IN? Maabo Kludze, PharmD, MBA, CDE, BCPS, Associate Director Elizabeth A. Shlom, PharmD, BCPS, SVP & Director Clinical Pharmacy Program Acurity, Inc. Privileged and Confidential August 15, 2017 Privileged and Confidential Program Objectives By the end of the presentation, the pharmacist or pharmacy technician participant will be able to: ◆ Identify orphan drugs and first-in-class medications approved by the FDA in 2016. ◆ Describe the role of new agents approved for use in oncology patients. ◆ Identify and discuss the role of novel monoclonal antibodies. ◆ Discuss at least two new medications that address public health concerns. Neither Dr. Kludze nor Dr. Shlom have any conflicts of interest in regards to this presentation. Privileged and Confidential 2016 NDA Approvals (NMEs/BLAs) ◆ Nuplazid (primavanserin) P ◆ Adlyxin (lixisenatide) ◆ Ocaliva (obeticholic acid) P, O ◆ Anthim (obitoxaximab) O ◆ Rubraca (rucaparib camsylate) P, O ◆ Axumin (fluciclovive F18) P ◆ Spinraza (nusinersen sodium) P, O ◆ Briviact (brivaracetam) ◆ Taltz (ixekizumab) ◆ Cinqair (reslizumab) ◆ Tecentriq (atezolizumab) P ◆ Defitelio (defibrotide sodium) P, O ◆ Venclexta (venetoclax) P, O ◆ Epclusa (sofosburvir and velpatasvir) P ◆ Xiidra (lifitigrast) P ◆ Eucrisa (crisaborole) ◆ Zepatier (elbasvir and grazoprevir) P ◆ Exondys 51 (eteplirsen) P, O ◆ Zinbyrta (daclizumab) ◆ Lartruvo (olaratumab) P, O ◆ Zinplava (bezlotoxumab) P ◆ NETSTPOT (gallium Ga 68 dotatate) P, O O = Orphan; P = Priority Review; Red = BLA Privileged and Confidential History of FDA Approvals Privileged and Confidential Orphan Drugs ◆FDA Office of Orphan Products Development • Orphan Drug Act (1983) – drugs and biologics . “intended for safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the U.S.
    [Show full text]
  • Bezlotoxumab (Zinplava®)
    Zinplava Swiss Risk Management Plan Summary V1.5 Swiss Summary of the Risk Management Plan (RMP) for Zinplava® (Bezlotoxumab 1000mg) Concentrate for solution for infusion Version 1.5 (November 2016) The Risk Management Plan (RMP) is a comprehensive document submitted as part of the application dossier for market approval of a medicine. The RMP summary contains information on the medicine's safety profile and explains the measures that are taken in order to further investigate and follow the risks as well as to prevent or minimise them. The RMP summary of Zinplava® is a concise document and does not claim to be exhaustive. As the RMP is an international document, the summary might differ from the “Arzneimittelinformation / Information sur le médicament” approved and published in Switzerland, e.g. by mentioning risks occurring in populations or indications not included in the Swiss authorisation. Please note that the reference document which is valid and relevant for the effective and safe use of Zinplava® in Switzerland is the “Arzneimittelinformation / Information sur le médicament” (see www.swissmedicinfo.ch) approved and authorized by Swissmedic. MSD Merck Sharp & Dohme AG is fully responsible for the accuracy and correctness of the content of the published summary RMP of Zinplava®. Zinplava Swiss Risk Management Plan Summary V1.5 1 Elements for Summary Tables in the EPAR 1.1 Summary Table of Safety Concerns Table 1 Summary of Safety Concerns Important identified risks None Important potential risks Infusion-related Reactions Including
    [Show full text]
  • Revenue Codes with Special Linkages
    INDIANA HEALTH COVERAGE PROGRAMS PROVIDER CODE TABLES Revenue Codes with Special Procedure Code Linkages Note: Due to possible changes in Indiana Health Coverage Programs (IHCP) policy or national coding updates, inclusion of a code on the code tables does not necessarily indicate current coverage. See IHCP Banner Pages and Bulletins and the IHCP Fee Schedules for updates to coding, coverage, and benefit information. For information about using this code table, see the Claim Submission and Processing provider reference module. Table 1 – Procedure Codes Linked to Revenue Code 260 – IV Therapy – General Table 2 – Procedure Codes Linked to Revenue Code 274 – Prosthetic/Orthotic Devices Table 3 – Procedure Codes Linked to Revenue Code 636 – Drugs Requiring Detailed Coding Table 4 – Procedure Code Linked to Revenue Code 724 – Labor Room/Delivery – Birthing Center Table 5 – Procedure Codes Linked to Revenue Code 920 – Other Diagnostic Services – General Table 6 – Procedure Codes Linked to Revenue Code 929 – Other Diagnostic Services Table 7 – Procedure Codes Linked to Revenue Code 940 – Other Therapeutic Services – General Table 8 – Procedure Codes Linked to Revenue Codes for Managed Care Billing Only (Revenue Codes 912, 913, and 960) Published: September 16, 2021 1 Indiana Health Coverage Programs Revenue Codes with Special Procedure Code Linkages Table 1 – Procedure Codes Linked to Revenue Code 260 – IV Therapy – General Reviewed/Updated: June 8, 2021 Note: The procedure codes in this table may be billed with revenue code 260 to receive separate reimbursement when billed on the same date of service as a treatment room revenue code. Injection administration (including vaccine administration) is included in the reimbursement for treatment rooms.
    [Show full text]
  • 761046Orig1s000
    CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 761046Orig1s000 MICROBIOLOGY/VIROLOGY REVIEW(S) Division of Anti-Infective Products Clinical microbiology Review BLA761046 Bezlotoxumab BLA: 761046 Date Submitted: 11-22-15 Date Received by CDER: 11-23-15 Date Assigned: 12-1-15 Date Completed: 4-19-16 Reviewer: Kerian Grande Roche, Ph.D. APPLICANT: Merck Sharp and Dohme Corp., a subsidiary of Merck and Co., Inc. (Merck) DRUG PRODUCT NAMES: Proprietary: Bezlotoxumab Nonproprietary: CDB1, MK6072 Antibody Class: IgG1/kappa isotype subclass Molecular Weight: 148.2 kDa DRUG CATEGORY: Human monoclonal antibody to C. difficile Toxin B PROPOSED INDICATION: Prevention of Clostridium difficile infection (CDI) recurrence in patients 18 years or older receiving antibiotic therapy for CDI PROPOSED DOSAGE FORM, STRENGTH, ROUTE OF ADMINISTRATION AND DURATION OF TREATMENT: MK-6072 drug product is a sterile, aqueous solution. Vials contain a target deliverable dose of 40 mL of 25mg/mL MK-6072 for a total of 1000 mg per vial. MK-6072 drug product is diluted (b) (4) prior to administration. The recommended dose of bezlotoxumab is 10 mg/kg by intravenous infusion over 60 minutes in one dose. DISPENSED: Rx RELATED PRODUCTS: N/A REMARKS: This submission is for an original Biologics License Application (BLA) for bezlotoxumab injection for intravenous use. Bezlotoxumab (MK-6072) is a fully human monoclonal antibody (mAb) of the IgG1/kappa isotype subclass that binds to Clostridium difficile (C. difficile) toxin B. CONCLUSIONS AND RECOMMENDATIONS: From clinical microbiology perspective, this BLA submission is approvable pending an accepted version of the labeling. See FDA’s proposed version of the microbiology section of the labeling below (this may not be the final Agency label as discussions are still ongoing).
    [Show full text]
  • Medicines/Pharmaceuticals of Animal Origin V3.0 November 2020
    Medicines/pharmaceuticals of animal origin V3.0 November 2020 Medicines/pharmaceuticals of animal origin - This guideline provides information for all clinical staff within Hospital and Health Services (HHS) on best practice for avoidance of issues related to animal products. Medicines/pharmaceuticals of animal origin - V3.0 November 2020 Published by the State of Queensland (Queensland Health), November 2020 This document is licensed under a Creative Commons Attribution 3.0 Australia licence. To view a copy of this licence, visit creativecommons.org/licenses/by/3.0/au © State of Queensland (Queensland Health) 2020 You are free to copy, communicate and adapt the work, as long as you attribute the State of Queensland (Queensland Health). For more information contact: Medication Services Queensland, Queensland Health, GPO Box 48, Brisbane QLD 4001, email [email protected] An electronic version of this document is available at https://www.health.qld.gov.au/__data/assets/pdf_file/0024/147507/qh-gdl-954.pdf Disclaimer: The content presented in this publication is distributed by the Queensland Government as an information source only. The State of Queensland makes no statements, representations or warranties about the accuracy, completeness or reliability of any information contained in this publication. The State of Queensland disclaims all responsibility and all liability (including without limitation for liability in negligence) for all expenses, losses, damages and costs you might incur as a result of the information being inaccurate
    [Show full text]
  • CDER Therapeutic Biologic Products List
    CDER Therapeutic Biologic Products This list is intended to include all the Center for Drug Evaluation and Research (CDER) user fee billable therapeutic biological products and potencies approved under Section 351 of the Public Health Service Act. The Orange Book includes a section entitled "Drug Products with Approval under Section 505 of the Act Administered by CBER." Included on that list are several products that have been transferred to CDER which would be considered billable also. Program fees are assessed for each potency in which the approved (non-revoked, non-suspended) product is manufactured in final dosage form. When evaluating the specific strength or potency of a drug in final dosage form for purposes of assessing program fees for liquid parenteral biological products, CDER intends to take into consideration both the total amount of drug substance in mass or units of activity in a product and the concentration of drug substance (mass or units of activity per unit volume of product). Biologic products considered to have a different strength or potency in a final dosage form will be given separate entries in the Biologics List and assessed separate program fees. An auto-injector that has the same strength or potency as a prefilled syringe or vial will generally be assessed a separate prescription drug program fee. In certain circumstances, products which have been discontinued from marketing but are still licensed are not assessed program fees. Those products are identified on the CDER Discontinued Biologic Product List section. The potency information contained in this list is based on information in our database.
    [Show full text]
  • ENTRY WATCH 2016 Published by the Patented Medicine Prices Review Board June 2018 Meds Entry Watch, 2016 Is Available in Electronic Format on the PMPRB Website
    MEDS ENTRY WATCH 2016 Published by the Patented Medicine Prices Review Board June 2018 Meds Entry Watch, 2016 is available in electronic format on the PMPRB website. Une traduction de ce document est également disponible en français sous le titre : Veille des médicaments mis en marché, 2016 Patented Medicine Prices Review Board Standard Life Centre Box L40 333 Laurier Avenue West Suite 1400 Ottawa, ON K1P 1C1 Tel.: 1-877-861-2350 TTY 613-288-9654 Email: [email protected] Web: www.pmprb-cepmb.gc.ca ISSN 2560-6204 Cat. No.: H79-12E-PDF © Her Majesty the Queen in Right of Canada, as represented by the NPDUIS initiative of the Patented Medicine Prices Review Board, 2018 MEDS ENTRY WATCH 2016 About the PMPRB Acknowledgements The Patented Medicine Prices Review Board This report was prepared by the Patented (PMPRB) is a respected public agency that makes Medicine Prices Review Board (PMPRB) a unique and valued contribution to sustainable as part of the National Prescription Drug spending on pharmaceuticals in Canada by: Utilization Information System (NPDUIS). ~ providing stakeholders with price, cost and The PMPRB would like to acknowledge the utilization information to help them make timely contributions of and knowledgeable drug pricing, purchasing and ~ The members of the NPDUIS Advisory reimbursement decisions; and Committee for their expert oversight and ~ acting as an effective check on the patent rights guidance in the preparation of this report. of pharmaceutical manufacturers through the ~ PMPRB NPDUIS staff for their contribution responsible and efficient use of its consumer to the analytical content of the report: protection powers.
    [Show full text]
  • FDA Briefing Document Bezlotoxumab Injection Meeting of the Antimicrobial Drugs Advisory Committee (AMDAC) June 9, 2016
    FDA Briefing Document Bezlotoxumab Injection Meeting of the Antimicrobial Drugs Advisory Committee (AMDAC) June 9, 2016 The committee will discuss biologic license application (BLA) 761046 bezlotoxumab injection, submitted by Merck Sharpe & Dohme Corp., for the proposed indication of prevention of Clostridium difficile infection (CDI) recurrence. 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 bezlotoxumab injection to this Advisory Committee in order to gain the Committee’s insights and opinions, and the background package may not include all issues relevant to the final regulatory recommendation and instead is intended to focus on issues identified by the Agency for discussion by the Advisory Committee. 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. The final determination may be affected by issues not discussed at the advisory committee meeting. 2 Table of Contents 1 Introduction ................................................................................................................
    [Show full text]
  • Drug Consumption at Wholesale Prices in 2017 - 2020
    Page 1 Drug consumption at wholesale prices in 2017 - 2020 2020 2019 2018 2017 Wholesale Hospit. Wholesale Hospit. Wholesale Hospit. Wholesale Hospit. ATC code Subgroup or chemical substance price/1000 € % price/1000 € % price/1000 € % price/1000 € % A ALIMENTARY TRACT AND METABOLISM 321 590 7 309 580 7 300 278 7 295 060 8 A01 STOMATOLOGICAL PREPARATIONS 2 090 9 1 937 7 1 910 7 2 128 8 A01A STOMATOLOGICAL PREPARATIONS 2 090 9 1 937 7 1 910 7 2 128 8 A01AA Caries prophylactic agents 663 8 611 11 619 12 1 042 11 A01AA01 sodium fluoride 610 8 557 12 498 15 787 14 A01AA03 olaflur 53 1 54 1 50 1 48 1 A01AA51 sodium fluoride, combinations - - - - 71 1 206 1 A01AB Antiinfectives for local oral treatment 1 266 10 1 101 6 1 052 6 944 6 A01AB03 chlorhexidine 930 6 885 7 825 7 706 7 A01AB11 various 335 21 216 0 227 0 238 0 A01AB22 doxycycline - - 0 100 0 100 - - A01AC Corticosteroids for local oral treatment 113 1 153 1 135 1 143 1 A01AC01 triamcinolone 113 1 153 1 135 1 143 1 A01AD Other agents for local oral treatment 49 0 72 0 104 0 - - A01AD02 benzydamine 49 0 72 0 104 0 - - A02 DRUGS FOR ACID RELATED DISORDERS 30 885 4 32 677 4 35 102 5 37 644 7 A02A ANTACIDS 3 681 1 3 565 1 3 357 1 3 385 1 A02AA Magnesium compounds 141 22 151 22 172 22 155 19 A02AA04 magnesium hydroxide 141 22 151 22 172 22 155 19 A02AD Combinations and complexes of aluminium, 3 539 0 3 414 0 3 185 0 3 231 0 calcium and magnesium compounds A02AD01 ordinary salt combinations 3 539 0 3 414 0 3 185 0 3 231 0 A02B DRUGS FOR PEPTIC ULCER AND 27 205 5 29 112 4 31 746 5 34 258 8
    [Show full text]
  • A Abacavir Abacavirum Abakaviiri Abagovomab Abagovomabum
    A abacavir abacavirum abakaviiri abagovomab abagovomabum abagovomabi abamectin abamectinum abamektiini abametapir abametapirum abametapiiri abanoquil abanoquilum abanokiili abaperidone abaperidonum abaperidoni abarelix abarelixum abareliksi abatacept abataceptum abatasepti abciximab abciximabum absiksimabi abecarnil abecarnilum abekarniili abediterol abediterolum abediteroli abetimus abetimusum abetimuusi abexinostat abexinostatum abeksinostaatti abicipar pegol abiciparum pegolum abisipaaripegoli abiraterone abirateronum abirateroni abitesartan abitesartanum abitesartaani ablukast ablukastum ablukasti abrilumab abrilumabum abrilumabi abrineurin abrineurinum abrineuriini abunidazol abunidazolum abunidatsoli acadesine acadesinum akadesiini acamprosate acamprosatum akamprosaatti acarbose acarbosum akarboosi acebrochol acebrocholum asebrokoli aceburic acid acidum aceburicum asebuurihappo acebutolol acebutololum asebutololi acecainide acecainidum asekainidi acecarbromal acecarbromalum asekarbromaali aceclidine aceclidinum aseklidiini aceclofenac aceclofenacum aseklofenaakki acedapsone acedapsonum asedapsoni acediasulfone sodium acediasulfonum natricum asediasulfoninatrium acefluranol acefluranolum asefluranoli acefurtiamine acefurtiaminum asefurtiamiini acefylline clofibrol acefyllinum clofibrolum asefylliiniklofibroli acefylline piperazine acefyllinum piperazinum asefylliinipiperatsiini aceglatone aceglatonum aseglatoni aceglutamide aceglutamidum aseglutamidi acemannan acemannanum asemannaani acemetacin acemetacinum asemetasiini aceneuramic
    [Show full text]
  • Assessment of Efficacy of Bezlotoxumab for Prevention of Clostridium Difficile Infection Recurrence by Diagnostic Test Method
    P1341 European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 2016 RAI Amsterdam, 1 2 3 4 4 4 4 4 4 Amsterdam, Wilcox MH ; Rahav G ; Dubberke E ; Gabryelski L ; Eves K ; Tipping R ; Guris D ; Kartsonis N ; Dorr MB The Netherlands Assessment of Effi cacy of Bezlotoxumab for Prevention of 1University of Leeds, Leeds, West Yorkshire, UK; 2Sheba Medical Center, Tel Hashomer, Israel; April 09–12, 2016 Clostridium diffi cile Infection Recurrence by Diagnostic Test Method 3Washington University School of Medicine, St Louis, MO, USA; 4Merck & Co., Inc., Kenilworth, NJ, USA Diagnostic Tests Table 1. Subject baseline characteristics (MODIFY I and II pooled data) • CDI recurrence rates were lower among subjects receiving bezlotoxumab compared Table 3. Diagnosis methods for the recurrent episodes of CDI (MODIFY I and II Introduction and Purpose with placebo (17% vs 27%; adjusted difference Ϫ10.0, 95% confi dence interval pooled data) • The baseline CDI episode was diagnosed based on results of stool tests performed Bezlotoxumab + SOC Placebo + SOC [–14.0,–6.0], p<0.0001) (Figure 3A) at the local laboratory Bezlotoxumab Placebo • It has been estimated that Clostridium diffi cile causes at least 172,000 infections each Number of subjects (%) Total • Among bezlotoxumab-treated subjects, CDI recurrence rates were higher when + SOC + SOC year across the 27 countries of the European Union among individuals у2 years of • Permitted diagnostic testing methods included N=335 age.1,2 However, these data do not take into account a recently documented 70% Subject characteristics (N=781) (N=773) diagnosis was made by PCR compared with toxin EIA (Figure 3B) n=129 n=206 – Cell cytotoxicity assay Local laboratory Central laboratorya Number of subjects (%) increase in incidence of C.
    [Show full text]
  • Dostupnost Antiinfektiv V České Republice
    aktuálně ročník 27 | číslo 5/2017 LÉKY A PRÁVO Dostupnost antiinfektiv v České republice MVDr. Veronika Valdová Arete‑Zoe, LLC Souhrn Valdová V. Dostupnost antiinfektiv v České republice. Remedia 2017; 27: 509–513. na Seznamu nepostradatelných léčiv Světové zdravotnické organizace figuruje 119 antiinfektiv, z nichž v České republice není registrováno 29. Dalších 10 léčiv je registrováno, ale neobchodováno. Dostupnost antibiotik a dalších nezbytných léčiv má přímý dopad na klinickou praxi. Příkladem je aktuali- zovaný postup pro léčbu sepse a septického šoku, který doporučuje deeskalaci a zacílení na identifikovaný patogen ihned po jeho identifikaci z důvodu snížení zátěže pro organismus pacienta. aktualizované léčebné postupy je nutno brát v úvahu při sestavování národních seznamů nepostradatelných léčiv. Z nepostradatelných tuberkulostatik a antivirotik chybějí v ČR některé fixní kombinace určené pro první linii léčby tuberkulózy a HIV/aIDS. Padělky léčivých přípravků a nedoléčené infekce jsou hlavními příčinami vzniku multirezistentních kmenů původce tuberkulózy. Z hyperimunních sér v ČR chybí sérum proti záškrtu. Vakcíny se potýkají s celosvětovým nedostatkem v důsledku délky a náročnosti výroby. Klíčová slova: antiinfektiva – nepostradatelná léčiva – dostupnost léčiv – nedostatek léčiv – tuberkulóza – HIV/aIDS – sepse. Summary Valdova V. Availability of antiinfectives in the Czech Republic. Remedia 2017; 27: 509–513. the World Health Organization (WHO) lists 119 antiinfectives on the list of essential medicines. Of these, 29 are not registered in the Czech Republic, and another 10 are registered but not marketed. availability of antimicrobials and other essential medicines directly affects clinical practice. One such example is the newly revised guidelines for the treatment of sepsis and septic shock, which recommends deescalation of antibiotic treatment and targeting the causative pathogen immediately after its identification to minimize toxicity to the patient’s metabolism.
    [Show full text]