The clinical pharmacology and drug interactions of bedaquiline
|
|
- Jonah Cooper
- 6 years ago
- Views:
Transcription
1 7 TH FIDSSA 2017 The clinical pharmacology and drug interactions of bedaquiline Helen McIlleron Division of Clinical Pharmacology University of Cape Town
2 20 years 2 drugs
3 conditional approval based on phase IIb clinical data in drug-resistant TB: Time to sputum-culture conversion Diacon AH et al. N Engl J Med 2014;371:
4 (limited) roll-out Indications - Pre-XDR, XDR, insufficient tolerated and effective drugs ± 8200 patients had bedaquiline before March 2017, 60% in South Africa scant use in children and adolescents (Achar et al., Emerging Infect Dis 2017) very few pregnant women outcomes - retrospective multicentre study, n=428, 46% XDR-TB (Borisov et al., Eur Respir J 2017; 49: ) median time to culture conversion(cc): 60 (33-90)d 3 month CC: 81% end of treatment CC: 92% development of resistance is a concern, and is potentially an indicator of sub-optimal use
5 basics PK in patients PK-PD DDIs
6 bedaquiline diarylquinoline lipophilic, basic cationic amphiphilic (CAD) phospholipidosis protein binding >99.9% M6 (aldehyde) M2 CYP3A4 CYP2C8, -18, -19 CYP1A1 N-didesmethyl BDQ (M3) hydroxyl metabolites Smyej et al., Toxicologic Pathology 2017, Vol. 45(5) ; Nan Zheng et al. J Pharmacol Exp Ther 2011;336:
7 bedaquiline s target - mycobacterial ATP synthase Image: Dheda et al., Int J Tuberc Lung Dis 2016; 20(12):S24 S32
8 % 0 MIC, mg/l MICs for baseline isolates from patients with DR-TB ( phase 2b studies, n=347; Chinese XDR-TB patients, n=90) Villellas C et al., J Antimicrob Chemother 2017; 72: ; Pang et al., Antimicrob Agents Chemother 2017; 61:e
9 resistance mechanisms - target mutations in atpe - nontarget mutations in Rv0678 Andries K, PLoS ONE 9(7): e102135; image- Dheda et al., Int J Tuberc Lung Dis 2016; 20(12):S24 S32
10 PK high variability in plasma concentrations Loading dose (400 mg/d x 14 d) maintenance (200 mg 3 x/week) to 6-months terminal t 1/2 ± 5 months Healan AM et al., Antimicrob Agents Chemother 2017; doi: /aac post-treatment exposures Svensson EM et al., CPT Pharmacometrics Syst. Pharmacol. 2016; 5:
11 concomitant FOOD PK + albumin - exposure weight - age - African - Svensson EM et al., CPT Pharmacometrics Syst. Pharmacol. 2016; 5:
12 bedaquiline PK efficacy Bedaquiline AUC (mg.h/l) in MDR-TB patients OBR only 0 bedaquiline + OBR 17.4 (L) (H) Svensson EM, Karlsson MO. J Antimicrob Chemother. 2017; doi: /jac/dkx317.
13 safety Guglielmetti L et al., Eur Respir J 2017; 49: % of 428 discontinued bedaquiline (Borisov et al. - multicentre retrospective study ) - 52% on clofazimine - 58% on moxifloxacin - 46% on amikacin/kanamycin - 82% on linezolid 1 cardiac arrythmia-related death/428 - hypokalaemia ±10% experience QTcF > 500 ms Pym AS et al., Eur Resp J : with delamanid - 2/5 patients had asymptomatic QT prolongation (Maryandyshev et al. Emerging Infect Dis 2017) ACTG 5343 ongoing
14 Diacon et al., AJRCCM 2015; 191(8): time-dependent QT-interval changes change in QTcB interval from baseline over time in combination regimens x 14 days
15 PK drug-drug interactions 1 st -line TB drugs rifampicin, rifapentine, isoniazid/ pyrazinamide 2 nd -line TB drugs rifabutin ART efavirenz, nevirapine, lopinavir/r
16 effects of rifampicin and rifapentine - in daily 600 mg doses BDQ BDQ +RIF BDQ +RPE Adjusted doses with rifampicin: BDQ 1000 mg/d *14d then 1000 mg 3x/wk Svensson EM et al., Antimicrob Chemother 2015; 70:
17 van Heeswijk et al., ICAAC 2007 single dose bedaquiline, by rifabutin - AUC 10% Healan AM et al., Antimicrob Agents Chemother 2017; doi: /aac PK of bedaquiline, by INH/PZA combined, in 22 HNVs BDQ AUC 13% M2 AUC 30% INH AUC 7% PZA AUC 8% daily doses: 5d >7d 10 d 5d PZA 2 g INH 300 mg BDQ 400 mg
18 Svensson EM et al. AAC 2013;57(6): bedaquiline drug-drug interactions with ARVs efavirenz reduces bedaquiline exposure by 18% for single dose, by >50% at steady state! - cumulative effects bedaquiline M2 18
19 Bedaquiline and M2 concentrations over time, without ART, and with lopinavir- and nevirapine-based ART, respectively. 400 mg daily x 14 d 200 mg 3 x/week 300 mg daily x 14 d 100 mg 3 x/week Brill MJ et al., Int J Antimicrob Agents Feb;49(2):
20 impact of DDIs on bedaquiline efficacy Proportion patients without SCC at 20 w 12.3% 16.3% 8.4% 19.8% 25.3% Svensson EM et al. 9th International Workshop on Clinical Pharmacology of TB Drugs, Liverpool,
21 conclusions Bedaquiline has transformed outcomes in patients with otherwise weak regimens Appears to be relatively safe Dosing, treatment duration and companion drugs need to be optimized to reduce the emergence of resistance Understanding the PK-PD relationships will contribute to optimized use
Drug Interactions with ART and New TB drugs: What Do We Know?
Drug Interactions with ART and New TB drugs: What Do We Know? HIV/TB Research Frontiers Meeting 20 th Conference on Retroviruses and Opportunistic Infections 3 March 2013 Presented by: Kelly Dooley MD,
More informationHot Issues in Tuberculosis: Treatment of Latent TB Infection and New TB Drugs
Slide 1 Hot Issues in Tuberculosis: Treatment of Latent TB Infection and New TB Drugs Constance A. Benson, M.D. Professor of Medicine Division of Infectious Diseases University of California, San Diego
More informationA model-based analysis to describe bedaquiline s exposure-response relationship and predict the impact of drugdrug interactions
9th International Workshop on Clinical Pharmacology of TB Drugs 24 October 2016, Liverpool, UK A model-based analysis to describe bedaquiline s exposure-response relationship and predict the impact of
More informationCompassionate use of bedaquiline in highly drug-resistant tuberculosis patients in Mumbai, India
AGORA RESEARCH LETTER Compassionate use of bedaquiline in highly drug-resistant tuberculosis patients in Mumbai, India To the Editor: Bedaquiline, a mycobacterial ATP synthase inhibitor [1], is the first
More informationBedaquiline and delamanid combination as part of a MDR-TB treatment regimen: Current evidence and practices
Bedaquiline and delamanid combination as part of a MDR-TB treatment regimen: Current evidence and practices Cathy Hewison, Médecins Sans Frontières RESIST-TB 5 th April 2018 Outline Current recommendations
More informationMultiple Drug-resistant Tuberculosis: a Threat to Global - and Local - Public Health
Multiple Drug-resistant Tuberculosis: a Threat to Global - and Local - Public Health C. Robert Horsburgh, Jr. Boston University School of Public Health Background Outline Why does drug resistance threaten
More informationDosage and Administration
SIRTURO product information for healthcare providers 2 WARNINGS: An increased risk of death was seen in the SIRTURO (bedaquiline) treatment group (9/79, 11.4%) compared to the placebo treatment group (2/81,
More informationSirturo: a new treatment against multidrug resistant tuberculosis
Sirturo: a new treatment against multidrug resistant tuberculosis TB is an on-going problem WHO estimated incidence of new TB cases 2009 Global Tuberculosis Control: WHO report 2010. Available at: http://www.who.int/tb/publications/global_report/2010/en/index.html
More informationNew TB Medications. National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention New TB Medications Neha Shah MD MPH Field Medical Officer Tuberculosis Control Branch California Department of Public Health Centers
More informationNew Drugs, New Treatments, Shorter Regimens
New Drugs, New Treatments, Shorter Regimens Sarah K. Brode, MD MPH FRCP(C) West Park Healthcare Centre, University Health Network, University of Toronto TB Elimination: Back to Basics November 16, 2016
More informationMultidrug-resistant tuberculosis in children
Multidrug-resistant tuberculosis in children James Seddon Clinical Lecturer Imperial College London UCL-TB and LSHTM TB Centre World TB Day 2015 24th March 2015 Outline Burden Recent studies Preventive
More informationTRAITEMENT DE MYCOBACTERIUM TUBERCULOSIS MULTIRÉSISTANT
TRAITEMENT DE MYCOBACTERIUM TUBERCULOSIS MULTIRÉSISTANT LORENZO GUGLIELMETTI RICAI, 18 DÉCEMBRE 2017 CNR des Mycobactéries OUTLINE Introduction New regimens and new drugs New drugs in France Future perspectives
More informationHA Convention 2016 : Special Topic Session 3 May 2016
HA Convention 2016 : Special Topic Session 3 May 2016 Diagnosis and Management of TB in Adults Dr. Thomas Mok COS(RMD), KH Tuberculosis An airborne infectious disease caused by Mycobacterium tuberculosis
More informationNew Frontiers: Innovation and Access
8 th Regional TB Symposium - Tashkent, Uzbekistan New Frontiers: Innovation and Access New Guidelines: An Opportunity for National Programmes and Patients: Evidence for new WHO recommendations on MDR-TB
More informationUsing delamanid in MDR-TB Francis Varaine MSF
Using delamanid in MDR-TB Francis Varaine MSF Symposium on new treatment and approaches to Tuberculosis Yerevan TB February 2015 A new anti-tb drug Nitro-dihydro-imidazo-oxazole derivative Mechanism of
More information11 th Intl Workshop on Clinical Pharmacology of HIV. TB ARV interactions. Helen McIlleron, Div. Clin. Pharm., Univ. Cape Town, South Africa
11 th Intl Workshop on Clinical Pharmacology of HIV TB ARV interactions Helen McIlleron, Div. Clin. Pharm., Univ. Cape Town, South Africa Antituberculosis DRUGS std. short course chemother. rifampicin
More informationPAEDIATRIC TB TRIAL UPDATE
PAEDIATRIC TB TRIAL UPDATE ANNEKE C. HESSELING PROFESSOR IN PAEDIATRICS AND CHILD HEALTH DIRECTOR: DESMOND TUTU TB CENTRE DEPARTMENT OF PAEDIATRICS AND CHILD HEALTH STELLENBOSCH UNIVERSITY, SOUTH AFRICA
More informationDevelopment of New Regimens for Tuberculosis Zhenkun Ma, Ph.D.
Development of New Regimens for Tuberculosis Chief Scientific Officer Global Alliance for TB Drug Development 40 Wall Street, 24th Floor New York, NY 10005 USA 1 Outline What are the unmet needs in TB
More informationPharmacology and Pharmacokinetics of TB Drugs Part I
Pharmacology and Pharmacokinetics of TB Drugs Part I Charles A. Peloquin, Pharm. D. Professor, and Director Infectious Disease Pharmacokinetics Laboratory College of Pharmacy and The Emerging Pathogens
More informationCurrent Status in the Development of the New Anti-Tuberculosis Drugs
National Scientific Meeting TB UPDATE IX 2017 WORKSHOP AND SYMPOSIUM Novel Management to End TB Hotel Bumi Surabaya 29-30 April 2017 Current Status in the Development of the New Anti-Tuberculosis Drugs
More informationN AB I L A I S M AI L
Evaluation of methods for generation of in vitro mutants resistant to bedaquiline, clofazimine and linezolid using Mycobacterium tuberculosis reference strains NABILA ISMAIL 1, SHAHEED V OMAR 2, NAZIR
More informationProgrammatic introduction of newer drugs for drug-resistant tuberculosis
Programmatic introduction of newer drugs for drug-resistant tuberculosis Overview, clinical considerations, ethical issues, and informed consent Dr. Vivian Cox and Dr. Sein Sein Thi USAID StopTB Partnership
More informationCLINICAL EXPERIENCE OF TREATING XDR- TB AT JOSE PEARSON TB HOSPITAL
CLINICAL EXPERIENCE OF TREATING XDR- TB AT JOSE PEARSON TB HOSPITAL BY DR LIMPHO RAMANGOAELA B.Sc.Ed(NUL),MBCHB(UKZN) 20 TH OCTOBER 2017 Livingstone Resource Centre. JOSE PEARSON TB HOSPITAL Out Line Overview
More informationBEDAQUILINE (Sirturo)
An Activist s Guide to tag@treatmentactiongroup.org www.treatmentactiongroup.org BEDAQUILINE (Sirturo) By Erica Lessem and Lindsay McKenna February 2013 I. Introduction New drugs are urgently needed to
More informationNEW DRUGS FOR TUBERCULOSIS: THE NEED, THE HOPE AND THE REALITY
NEW DRUGS FOR TUBERCULOSIS: THE NEED, THE HOPE AND THE REALITY Neil W. Schluger, M.D. Professor of Medicine, Epidemiology and Environmental Health Sciences Columbia University Global tuberculosis incidence
More informationFinal Results from Stage 1 of a Double-Blind, Placebo- Controlled Trial with TMC207 in Patients with Multi- Drug Resistant (MDR)
Final Results from Stage 1 of a Double-Blind, Placebo- Controlled Trial with TMC207 in Patients with Multi- Drug Resistant (MDR) Tuberculosis (TB). AH Diacon*, A Pym**, MP Grobusch, G. Churchyard, T De
More informationPharmacokinetics and doses of antituberculosis drugs in children
Pharmacokinetics and doses of antituberculosis drugs in children HS Schaaf Desmond Tutu TB Centre Department of Paediatrics and Child Health Stellenbosch University Declarations I have no conflict of interest
More informationVC 2016 ASCPT All rights reserved
Citation: CPT Pharmacometrics Syst. Pharmacol. (2016) 5, 682 691; VC 2016 ASCPT All rights reserved doi:.02/psp4.12147 ORIGINAL ARTICLE Population Pharmacokinetics of Bedaquiline and Metabolite M2 in Patients
More informationNewer anti-tb drugs and regimens. DM Seminar
Newer anti-tb drugs and regimens DM Seminar 31-10-14 Why are newer drugs/regimens needed? Problems with current drugs/regimens Drug resistance Drug interaction of anti-tubercular drugs with ART Long duration
More informationTBTC research update: are we ready for 3 month treatment? 2009 TBTC Recompetition. NTCA presentation outline
TBTC research update: are we ready for 3 month treatment? Stefan Goldberg, MD Project officer, TBTC Studies 27, 28, 29 Tuberculosis Trials Consortium (TBTC) CDC Division of TB Elimination NTCA breakout
More informationTB Updates for the Physician Rochester, Minnesota June 19, 2009
TB Updates for the Physician Rochester, Minnesota June 19, 2009 Recent Findings & Activities of the Tuberculosis Trials Consortium (TBTC) Bill Burman Denver TBTC Unit & Denver Public Health Recent findings
More informationPharmacometric Models to Improve Treatment of Tuberculosis
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy 214 Pharmacometric Models to Improve Treatment of Tuberculosis ELIN M SVENSSON ACTA UNIVERSITATIS UPSALIENSIS UPPSALA
More informationWhat He Said: Rifampin versus Rifapentine
What He Said: Rifampin versus Rifapentine Charles A. Peloquin, Pharm.D. Director Infectious Disease Pharmacokinetics Laboratory Professor, College of Pharmacy & The Emerging Pathogens Institute University
More informationAnri Uys (MSc Pharmacology, BPharm NWU) Medicines Information Centre, Division of Clinical Pharmacology University of Cape Town
Anri Uys (MSc Pharmacology, BPharm NWU) Medicines Information Centre, Division of Clinical Pharmacology University of Cape Town Since March 2008 26 700 Queries to date 450 Queries per month South Africa:
More informationThe contribution of bedaquiline to the treatment of MDRTB
WHO/STB Expert Group Meeting Geneva, 29-30 January 2013 The contribution of bedaquiline to the treatment of MDRTB Synthesis of publicly available evidence Prepared by Bernard Fourie, PhD Commissioned by
More informationTuberculosis: update 2013
Tuberculosis: update 2013 William R. Bishai, MD, PhD Center for TB Research Division of Infectious Diseases Department of Medicine Johns Hopkins School of Medicine Question 1 A TB speaker at a major conference
More informationLABORATORY BASED DST FOR BEDAQUILINE AND INTRODUCTION IN COUNTRIES
LABORATORY BASED DST FOR BEDAQUILINE AND INTRODUCTION IN COUNTRIES NDWG Annual meeting 2015, Cape Town, South Africa Rigouts Leen, Institute of Tropical Medicine, Antwerp, Belgium 1 Bedaquiline (BDQ) Sirturo
More informationMaha R Farhat, MD MSc Massachusetts General Hospital Harvard Medical School. I have no financial or other potential conflicts of interest to disclose
Maha R Farhat, MD MSc Massachusetts General Hospital Harvard Medical School I have no financial or other potential conflicts of interest to disclose Update on the epidemiology of TB drug resistance Success
More informationSIRTURO (bedaquiline) tablets, for oral use Initial U.S. Approval 2012
HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use SIRTURO safely and effectively. See full prescribing information for SIRTURO. SIRTURO (bedaquiline)
More informationIssues in TB Drug Development: TB/HIV
Issues in TB Drug Development: TB/HIV Open Forum Gavin Churchyard 18 th August 2010 Presentation outline TB/HIV Epidemiology clinical aspects HIV associated TB Drug-Drug interactions Immunotherapy Latent
More informationPZA: A New Look Based on RNASeq, the Hollow Fiber System, and Patient Level Data. Tawanda Gumbo
PZA: A New Look Based on RNASeq, the Hollow Fiber System, and Patient Level Data Tawanda Gumbo Office of Global Health University of Texas Southwestern Medical Center, Dallas, Texas The team: this work
More informationMarcos Burgos, MD has the following disclosures to make:
Guidelines for the Treatment of Tuberculosis Marcos Burgos, MD May 13, 2015 TB for Pulmonologist March 13, 2015 Phoenix, AZ EXCELLENCE EXPERTISE INNOVATION Marcos Burgos, MD has the following disclosures
More informationBDQ/DLM COMBINATION: FRENCH-LATVIAN EXPERIENCE AND FUTURE PERSPECTIVES LORENZO GUGLIELMETTI RESIST-TB WEBINAR, 5 APRIL 2018
BDQ/DLM COMBINATION: FRENCH-LATVIAN EXPERIENCE AND FUTURE PERSPECTIVES LORENZO GUGLIELMETTI RESIST-TB WEBINAR, 5 APRIL 2018 OUTLINE New TB drugs in France and Latvia Bdq/Dlm: the French-Latvian experience
More informationActivity of PNU and its major metabolite in whole blood and broth culture models of TB
Activity of PNU 100480 and its major metabolite in whole blood and broth culture models of TB Paul Converse 1, Jin Lee 1, Kathy Williams 1, Opokua Amoabeng 1, Kim Dionne 1, Nicole Parish 1, Robert Wallis
More informationSIRTURO (bedaquiline) tablets, for oral use
HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use SIRTURO safely and effectively. See full prescribing information for SIRTURO. Initial U.S. Approval
More informationImpact of the interaction of R with rifampin on the. treatment of tuberculosis studied in the mouse model ACCEPTED
AAC Accepts, published online ahead of print on 21 July 2008 Antimicrob. Agents Chemother. doi:10.1128/aac.00566-08 Copyright 2008, American Society for Microbiology and/or the Listed Authors/Institutions.
More informationShorter TB regimens What is in de pipeline? Martin Boeree, Associate Professor Radboudumc, Nijmegen, the Netherlands Tuesday, 23 September, 2014
Shorter TB regimens What is in de pipeline? Martin Boeree, Associate Professor Radboudumc, Nijmegen, the Netherlands Tuesday, 23 September, 2014 Disclosures Clinical trials and studies funded by EDCTP,
More informationNew Drug Evaluation: Bedaquiline. Month/Year of Review: January 2014 End date of literature search: September 1, 2013
Copyright 2012 Oregon State University. All Rights Reserved Drug Use Research & Management Program Oregon State University, 500 Summer Street NE, E35, Salem, Oregon 97301-1079 Phone 503-947-5220 Fax 503-947-1119
More informationBedaquiline: 10 years later, the drug susceptibility testing protocol is still pending
EDITORIAL TUBERCULOSIS Bedaquiline: 10 years later, the drug susceptibility testing protocol is still pending Max Salfinger 1 and Giovanni Battista Migliori 2 Affiliations: 1 Dept of Medicine, National
More informationACCESS TO MEDICINES. Update on tuberculosis field activities
ACCESS TO MEDICINES Update on tuberculosis field activities Update on clinical activities 1/3 Latent TB Prevent study (S26) main study (8053 patients) PK substudy construction of a POPPK model Paediatric
More informationThe next generation of ART regimens
The next generation of ART regimens By Gary Maartens Presented by Dirk Hagemeister Division of Clinical Pharmacology UNIVERSITY OF CAPE TOWN IYUNIVESITHI YASEKAPA UNIVERSITEIT VAN KAAPSTAD Current state
More informationArticles. Funding Médecins Sans Frontières (MSF).
Early safety and efficacy of the combination of bedaquiline and delamanid for the treatment of patients with drug-resistant tuberculosis in Armenia, India, and South Africa: a retrospective cohort study
More informationThe QT Interval Safety Endpoint for DR- TB trials. Kelly Dooley & Gary Maartens (Disclaimer: I know very little cardiac electrophysiology)
The QT Interval Safety Endpoint for DR- TB trials Kelly Dooley & Gary Maartens (Disclaimer: I know very little cardiac electrophysiology) The ECG tracing Physiology of a cardiac myocyte Flow of ions (Na
More informationLusine Yeghiazaryan, Head of MDR Unit, RTBD NTC Armenia/MSF France
Feb 17 th -18 th 2015 Armenia Experience on Treatment of XDR and pre-xdr Patients with New drugs under Compassionate Use program Lusine Yeghiazaryan, Head of MDR Unit, RTBD NTC Armenia/MSF France Challenges
More informationChapter 5 Treatment. 5.1 First-Line Antituberculous Treatment
Chapter 5 Treatment Abstract In this chapter the treatment of drug sensitive and drug resistant TB and timing of antiretroviral treatment for HIV infected patients will be reviewed. Emphasis is placed
More informationTreatment of Tuberculosis
Treatment of Tuberculosis Marcos Burgos, MD April 5, 2016 TB Intensive April 5 8, 2016 San Antonio, TX EXCELLENCE EXPERTISE INNOVATION Marcos Burgos, MD has the following disclosures to make: No conflict
More informationMSF Field Research. Diagnosis and management of drug-resistant tuberculosis. South African adults. Hughes, J; Osman, M
MSF Field Research Diagnosis and management of drug-resistant tuberculosis in South African adults Authors Citation DOI Publisher Journal Rights Hughes, J; Osman, M Diagnosis and management of drug-resistant
More informationPharmacokinetics and safety of Moxifloxacin: Preliminary results of a dose escalation study
Pharmacokinetics and safety of Moxifloxacin: Preliminary results of a dose escalation study A.D. Pranger 1, W.C.M. de Lange 2, R. van Altena 2, P. van der Harst 3, M.P. van den Berg 3, D.R.A. Uges 1, J.G.W.
More informationHIV and TB coinfection: Updates. Awewura Kwara, MD, MPH &TM Associate Professor, Alpert Medical School of Brown University
HIV and TB coinfection: Updates Awewura Kwara, MD, MPH &TM Associate Professor, Alpert Medical School of Brown University Learning objectives Identify the optimal timing of antiretroviral therapy in patients
More informationSIRTURO. Bedaquiline NEW ZEALAND DATA SHEET
SIRTURO Bedaquiline NEW ZEALAND DATA SHEET 1. PRODUCT NAME SIRTURO 100 mg tablets. 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each tablet contains bedaquiline fumarate equivalent to 100 mg of bedaquiline.
More informationPharmacokinetics (PK) and Pharmacodynamics (PD) in the Treatment of Tuberculosis
Pharmacokinetics (PK) and Pharmacodynamics (PD) in the Treatment of Tuberculosis Shaun E. Gleason, PharmD, MGS Associate Professor, Department of Clinical Pharmacy Director, Distance Degrees and Programs
More informationShort Course Treatment for MDR TB
Objectives Short Course Treatment for MDR TB Barbara J Seaworth M.D. Medical Director Heartland National TB Center Professor of Medicine, University of Texas Health Northeast Participants will utilize
More informationANNEX I SUMMARY OF PRODUCT CHARACTERISTICS
ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1 This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked
More informationNIAID TB Therapeutic Clinical Research Priorities. Prognostic biomarkers for disease progression, treatment response/relapse
NIAID TB Therapeutic Clinical Research Priorities New drugs and combinations for DS and DR TB: Efficient Phase I and II evaluations Phase III Killing Persisters Sterilizing activity is crucial Prognostic
More informationA population pharmacokinetic model for rifampicin auto induction
A population pharmacokinetic model for rifampicin auto induction Paolo Denti 1, Wynand Smythe 1, Ulrika SH Simonsson 2, Roxana Rustomjee 3, Philip Onyebujoh 4, Peter Smith 1, Helen McIlleron 1 1 Division
More informationDelamanid and bedaquiline to treat multidrug-resistant and extensively drug-resistant tuberculosis in children: a systematic review
Review Article Delamanid and bedaquiline to treat multidrug-resistant and extensively drug-resistant tuberculosis in children: a systematic review Lia D Ambrosio 1,2, Rosella Centis 1, Simon Tiberi 3,
More informationProposal for a standardised treatment regimen to manage pre- and extensively drug-resistant tuberculosis cases
EDITORIAL TUBERCULOSIS Proposal for a standardised treatment regimen to manage pre- and extensively drug-resistant tuberculosis cases Jose A. Caminero 1,2, Alberto Piubello 2,3, Anna Scardigli 4 and 5
More informationCardiac safety of bedaquiline: a systematic and critical analysis of the evidence
EDITORIAL RESPIRATORY INFECTIONS AND TUBERCULOSIS Cardiac safety of bedaquiline: a systematic and critical analysis of the evidence Emanuele Pontali 1, Giovanni Sotgiu 2, Simon Tiberi 3,4, Lia D Ambrosio
More informationNon-rifampin rifamycins in TB/HIV
Non-rifampin rifamycins in TB/HIV Richard E. Chaisson, MD Johns Hopkins University Center for TB Research Consortium to Respond Effectively to the AIDS-TB Epidemic Rifamycins for TB Inhibit bacterial DNA-dependent
More informationTemporary Compliance Waiver Notice
Temporary Compliance Waiver Notice At the time of initial posting on November 26 th, 212, the attached PDF document may not be fully accessible to readers using assistive technology. A fully accessible
More informationTreatment of Active Tuberculosis
Treatment of Active Tuberculosis Jeremy Clain, MD Pulmonary & Critical Care Medicine Mayo Clinic October 16, 2017 2014 MFMER slide-1 Disclosures No relevant financial relationships No conflicts of interest
More informationMULTIDRUG- RESISTANT TUBERCULOSIS. Dean Tsukayama Hennepin County Medical Center Hennepin County Public Health Clinic
MULTIDRUG- RESISTANT TUBERCULOSIS Dean Tsukayama Hennepin County Medical Center Hennepin County Public Health Clinic I have no relevant financial relationships. Discussion includes off label use of: amikacin
More informationCertainty assessment of patients Effect Certainty Importance. a standardised 9 month shorter MDR-TB regimen. e f
Author(s): STREAM Stage 1 Trial investigators reported for the Guideline Development Group for the WHO treatment guidelines on MDR/RR-TB, 2018 update (6 July 2018) - FINAL RESULTS Question: PICO 1. In
More informationManagement of MDR TB. Dr Priscilla Rupali MD; DTM&H Professor and Head Department of Infectious Diseases Christian Medical College Vellore
Management of MDR TB Dr Priscilla Rupali MD; DTM&H Professor and Head Department of Infectious Diseases Christian Medical College Vellore Outline Global epidemiology of Tuberculosis Epidemiology of Tuberculosis
More informationTuberculosis: What's new in diagnos6cs and management?
Tuberculosis: What's new in diagnos6cs and management? Colin Menezes, Department of Internal Medicine, Chris Hani Baragwanath Academic Hospital, University of the Witwatersrand. Objec6ves of this talk:
More informationAnti-Infective Drugs Advisory Committee Meeting. Briefing Document. TMC207 (bedaquiline) Treatment of Patients with MDR-TB NDA
ADVISORY COMMITTEE BRIEFING MATERIALS: AVAILABLE FOR PUBLIC RELEASE 1 Anti-Infective Drugs Advisory Committee Meeting Briefing Document TMC207 (bedaquiline) Treatment of Patients with MDR-TB NDA 204-384
More informationClinical Trials Lecture 4: Data analysis
Clinical Trials Lecture 4: Data analysis Dick Menzies, MD Respiratory Epidemiology and Clinical Research Unit Montreal Chest Institute TB Research methods course July 17, 2014 Lecture 4: Data analysis
More informationSterilizing Activity of Novel TMC207- and PA-824-Containing Regimens in a Murine Model of Tuberculosis
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Dec. 2011, p. 5485 5492 Vol. 55, No. 12 0066-4804/11/$12.00 doi:10.1128/aac.05293-11 Copyright 2011, American Society for Microbiology. All Rights Reserved. Sterilizing
More informationThe shorter regimen for MDR-TB: evidence and pitfalls
The shorter regimen for MDR-TB: evidence and pitfalls Helen Cox 10 November 2017 What is the shortened regimen? Current conventional regimen (SA): Intensive Phase (at least 6 months): PZA / (EMB) / Kana
More informationOvercoming the Challenges in Access to TB Drugs for Children
Overcoming the Challenges in Access to TB Drugs for Children Gregory L. Kearns, PharmD, PhD Professor of Pediatrics and Pharmacology, University of Missouri Marion Merrell Dow / Missouri Chair in Pediatric
More informationOfficial ATS/CDC/IDSA Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis (Nahid et al, CID 2016)
Official ATS/CDC/IDSA Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis (Nahid et al, CID 2016) APPENDIX C: DRUGS IN CURRENT USE The U.S. Food and Drug Administration (FDA) has approved
More informationDiscovery & Development: Bedaquiline For Drug Resistant Tuberculosis. Wim Parys, MD Head R&D J&J Global Public Health
Discovery & Development: Bedaquiline For Drug Resistant Tuberculosis Wim Parys, MD Head R&D J&J Global Public Health - 500.000 Y (Turkey): TB infection suggestive bone lesions - 9000 Y (Alit-Yam, Israel)
More informationOptimising patient care in MDR TB with existing molecular screening tests in high burden countries
Optimising patient care in MDR TB with existing molecular screening tests in high burden countries Camilla Rodrigues MD Consultant Microbiologist Hinduja Hospital,India Outline What is the best empiric
More informationSupplementary Appendix
Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Zumla A, Raviglione M, Hafner R, von Reyn CF. Tuberculosis.
More informationPerspectives for new treatments for MDR-TB
Perspectives for new treatments for MDR-TB Life cycle of M. tuberculosis Active TB in 2015 10.4 million cases >1.4 million deaths Latent TB >2 billion cases Switzerland 564 cases (18 MDR) 2 Koul et al.
More informationHIV-TB co-infection: overview and recent update
HIV-TB co-infection: overview and recent update Brian Eley Paediatric Infectious Diseases Unit Red Cross War Memorial Children s Hospital School of Child and Adolescent Health University of Cape Town HIV
More information8/28/2017. Learning Objectives. After attending this presentation, learners will be able to:
New and Noteworthy in Tuberculosis Diagnostics and Treatment Susan Swindells, MBBS Professor of Internal Medicine University of Nebraska Medical Center Omaha, Nebraska San Antonio, Texas: August 21 to
More informationPrinciples and practice of treating drug-sensitive TB
Principles and practice of treating drug-sensitive TB Brian Eley Paediatric Infectious Diseases Unit Red Cross War Memorial Children s Hospital Department of Paediatrics and Child Health University of
More informationSurgery for MDR/XDR Tuberculosis
Surgery for MDR/XDR Tuberculosis John D. Mitchell, M.D. Davis Endowed Chair in Thoracic Surgery Professor and Chief, General Thoracic Surgery Department of Surgery University of Colorado School of Medicine
More informationTuberculosis and HIV: key issues in diagnosis and management
Tuberculosis and HIV: key issues in diagnosis and management Julian Elliott Infectious Diseases Unit, Alfred Hospital Centre for Population Health, Burnet Institute julian.elliott@alfred.org.au Outline
More informationOutline 8/2/2013. PK/PD PK/PD first-line drug กก PK/PD กก
Pharmacokinetic and pharmacodynamic of anti- tuberculosis drugs Outline PK/PD PK/PD first-line drug กก PK/PD กก Concentration vs time in tissue and other body fluids Pharmacologic or toxicologic effect
More informationThe treatment of patients with initial isoniazid resistance
The treatment of patients with initial isoniazid resistance 2011 INTERTB Meeting, St George s, London Patrick Phillips, MRC Clinical Trials Unit DA Mitchison, AJ Nunn. 21 st October 2011 Outline Background
More informationPopulation pharmacokinetics of bedaquiline (TMC207) and its M2 and M3 metabolites with efavirenz demonstrate reduced exposure
Population pharmacokinetics of bedaquiline (TMC207) and its M2 and M3 metabolites with efavirenz demonstrate reduced exposure Elin M Svensson 1 Kelly E Dooley 2, Francesca Aweeka 3, Jeong-Gun Park 4, Mats
More informationPhase III Clinical Trial Results at the 48 th Union World Conference on Lung Health: Implications for the Field 1
Phase III Clinical Trial Results at the 48 th Union World Conference on Lung Health: Implications for the Field 1 Preliminary results from two phase III drug-resistant TB (DR-TB) clinical trials were presented
More informationElizabeth A. Talbot MD Assoc Professor, ID and Int l Health Deputy State Epidemiologist, NH GEISELMED.DARTMOUTH.EDU GEISELMED.DARTMOUTH.
The image part with relationship ID rid2 was not found in the file. MDR TB Management Review of the Evolution (or Revolution?) Elizabeth A. Talbot MD Assoc Professor, ID and Int l Health Deputy State Epidemiologist,
More informationResearch gaps for eliminating TB deaths among people living with HIV. GJ Churchyard 25 th July 2017
Research gaps for eliminating TB deaths among people living with HIV GJ Churchyard 25 th July 2017 Overview Research gaps for preventing TB deaths among PLWHIV Programmatic management of LTBI Tests of
More informationTHE USE OF BEDAQUILINE IN THE TREATMENT OF MULTIDRUG RESISTANT TUBERCULOSIS EXPERT GROUP MEETING REPORT January 2013, Geneva
THE USE OF BEDAQUILINE IN THE TREATMENT OF MULTIDRUG RESISTANT TUBERCULOSIS EXPERT GROUP MEETING REPORT 29-30 January 2013, Geneva This report contains the collective views of an international group of
More informationWhat more is required to use rifamycin regimens to prevent TB in people living with HIV in resource constrained settings?
What more is required to use rifamycin regimens to prevent TB in people living with HIV in resource constrained settings? Gary Maartens Division of Clinical Pharmacology UNIVERSITY OF CAPE TOWN IYUNIVESITHI
More informationTB-CHAMP A PHASE 3 CLUSTER RANDOMIZED TRIAL FOR PREVENTION OF TB IN CHILD HOUSEHOLD CONTACTS
TB-CHAMP A PHASE 3 CLUSTER RANDOMIZED TRIAL FOR PREVENTION OF TB IN CHILD HOUSEHOLD CONTACTS ANNEKE C. HESSELING RESIST TB WEBINAR 20 APRIL 2017 DESMOND TUTU TB CENTRE PROFESSOR IN PAEDIATRICS AND CHILD
More informationThe Evaluation of Effectiveness and Safety of Novel Shorter. Treatment Regimens for Multidrug-Resistant Tuberculosis
The Evaluation of Effectiveness and Safety of Novel Shorter Treatment Regimens for Multidrug-Resistant Tuberculosis Operational Research Protocol Template May 2018 A publication of the Global Drug-resistant
More information