Terizidone.Pdf

Total Page:16

File Type:pdf, Size:1020Kb

Terizidone.Pdf Essential Medicines List (EML) 2015 Application for the inclusion of terizidone in the WHO Model List of Essential Medicines, as reserve second‐line drugs for the treatment of multidrug‐resistant tuberculosis (complementary lists of anti‐tuberculosis drugs for use in adults and children) General items 1. Summary statement of the proposal for inclusion, change or deletion This application concerns the updating of section 6.2.4 Antituberculosis medicines in the 2013 editions of both the WHO Model List of Essential Medicines (18th list) and the WHO Model List of Essential Medicines for Children (4th list)(1),(2). The proposal is to add terizidone to both the complementary list of anti‐tuberculosis medicines for adults and in children. Terizidone is not on the EML, but its sister medication, cycloserine, is on the complementary list in section 6.2.4 Antituberculosis medicines The applicant considers that terizidone should be viewed as an essential medicine for patients with multidrug‐resistant (MDR‐TB) and extensively drug‐resistant (XDR‐TB) disease. In many low resource settings, patients with these forms of tuberculosis are inadequately treated and often die because not enough medications are available to compose a suitable regimen (3). Second‐line drugs for the treatment of M/XDR‐TB are frequently not available; and global stock outs occur regularly. Terizidone should become more widely available to specialized care centres of national TB programmes and other health care providers treating M/XDR‐TB patients. The inclusion of terizidone as an anti‐tuberculosis agent on the EML will encourage pharmaceutical manufacturers to invest more in its production and will facilitate its inclusion in the national EML and its registration in countries where MDR and XDR‐TB are a health threat. Additionally, this harmonization of treatment regimens is key to medication price reduction through an increase in the volume of medications purchased. A major initiative to help enhance the treatment of TB and MDR‐TB patients has recently attracted UNITAID funding up to USD 60 million and aims to create new regimens using combinations of both the new TB medicines and older medications such as terizidone (5). This request to the EML is thus very timely and in line with the position of WHO and its technical partners on the subject. If approved, it would synergise with their concerted efforts to improve outcomes and reduce avoidable mortality for the close to half a million patients estimated to develop MDR‐TB in the world every year. Globally, 30% (95%CI: 24%–35%) of patients with MDR‐TB have resistance to a fluoroquinolone, a second‐line injectable agent, or both i.e. XDR‐TB. These patients would be eligible to receive regimens containing new and repurposed TB drugs, when options to treat them with existing drugs have been exhausted [3] 2. Name of the focal point in WHO submitting or supporting the application (where relevant) The focal point is the Unit of Laboratories, Diagnostics and Drug‐resistance of the Global TB Programme of WHO Headquarters (WHO/HTM/GTB/LDR). The technical personnel directly concerned are Dennis FALZON, Linh Nhat NGUYEN and Ernesto JARAMILLO. This application was prepared in close collaboration with WHO/GTB by Elizabeth HARAUSZ and the GRADE Tables (Sections 10 and 11) by Dick MENZIES. The guidance of Nicola MAGRINI of WHO/EMP in this work is acknowledged. 3. Name of the organization(s) consulted and/or supporting the application Not applicable. 4. International Nonproprietary Name (INN, generic name) of the medicine The WHO INN (generic name) is terizidone (6, 22, 23). 5. Formulation proposed for inclusion; including adult and paediatric (if appropriate) (1,2,4) The proposed formulation is 250 mg capsule for both adults and children. A drug information sheet for terizidone is attached as Annex 1 [4]. 6. International availability – sources, of possible manufacturers and trade names (4 , 26) Generic Drug Trade Names Availability Logistics Terizidone Terivalidin, Terizidon, Fatol in Germany is the only quality assured Tablets: no special storage or Terizidona source (27). However, Sanofi pharmaceuticals administrative needs. Store at manufactures terizidone in South Africa under room temperature in airtight the name “Terivalidin” and exports to Zambia, container. Angola, Mozambique, Botswana, Namibia and Kenya, with plans for future expansion (36). 7. Whether listing is requested as an individual medicine or as an example of a therapeutic group Terizidone is applying as an individual medicine without a square box symbol. 8. Information supporting the public health relevance (epidemiological information on disease burden, assessment of current use, target population) Each year it is estimated that half a million new MDR‐TB cases emerge in the world and over 200,000 MDR‐TB patients die (3). Many MDR‐TB cases go undetected and are not placed on appropriate treatment, increasing the risk that they die and/or transmit drug‐resistant strains to others. In 2013, countries reported that about 100,000 patients started MDR‐TB treatment worldwide. The effectiveness of these efforts vary considerably and data on outcome reporting in recent years showed that only about half the MDR‐TB patients complete their treatment successfully (9). The rest die, fail treatment, interrupt treatment, or are otherwise lost to follow up. Given the low treatment success of MDR and XDR‐TB, every effort must be made to ensure that all possible medications used to treat MDR and XDR‐TB are widely available. This is particularly the case in about one third of MDR‐TB cases who have lost susceptibility to fluoroquinolones, second‐line injectable agents, or both (i.e. XDR‐TB) (3). XDR‐TB represents about 9 % of MDR‐TB cases and some 100 countries have now detected at least one such case (3). The transmissibility of XDR‐TB strains has been documented in outbreaks and regular reports of cases without a previous history of TB treatment (28‐34); this poses a formidable, additional public health concern making the proper treatment of M/XDR‐TB patients all the more important. The likelihood of treatment success in MDR‐TB patients diminishes with the acquisition of additional resistance and is particularly low in XDR‐TB patients. The availability of all available possible medications to treat MDR/XDR‐TB is therefore essential to successfully treat these patients. 9. Treatment details (dosage regimen, duration; reference to existing WHO and other clinical guidelines; need for special diagnostics, treatment or monitoring facilities and skills) There are two main indications for terizidone in the treatment of MDR‐TB patients: 1) MDR‐TB treatment regimens : A typical MDR‐TB regimen is composed of pyrazinamide plus at least 4 second‐line anti‐TB drugs considered to be effective, including a later‐generation fluoroquinolones, a second‐line injectable, ethionamide (or prothionamide) and cycloserine or PAS(10). When one or more of these drugs are considered ineffective, as a result of in vitro resistance, severe intolerance, or prolonged use in the same patient, the regimen should be bolstered by “Group 5” drugs. Terizidone, which is a Group 4 drug, can be used in the place of cycloserine. 2) XDR‐TB regimens : XDR‐TB is difficult to treat. WHO guidelines recommend using pyrazinamide and any other Group 1 medication that may be effective, an injectable agent and a higher generation fluoroquinolone (if the strain retains susceptibility)(4). However, often these medications are no longer effective. Therefore, use of all Group 4 agents that are likely to be effective, use of 2 or more Group 5 drugs and consideration of high dose isoniazid and investigational drugs are recommended (4). As stated above, terizidone can be used in the place of cycloserine. Drug Treatment Regimen (4) Duration of Special diagnostics, treatment treatment or monitoring facilities and skills Terizidone Adults: 10‐15 mg/kg/day, can divide into 2 doses Duration of TB Baseline and monthly treatment Child: (>3kg and >28 days of age): 10‐20 mg/kg/day divided depression screening. every 12 hours (25) 10. Summary of comparative effectiveness in a variety of clinical settings: [See Annex 2] 11. Summary of comparative evidence on safety: [See Annex 2] 12. Summary of available data on comparative cost and cost‐effectiveness within the pharmacological class or therapeutic group: Drug Source Price (US$) Terizidone Global Drug Facility 250 mg: 79.40‐83.30/50 capsules MSH International Drug Price Indicator Guide 250 mg: 0.9152/tab Médecins sans Frontières (15) 250 mg: 1.513‐1.666/tab Regulatory information 13. Summary of regulatory status of the medicine (in various countries) The table below summarizes the regulatory status of terizidone vis‐à‐vis the stringent regulatory authorities and WHO’s Prequalification Programme. Drug Authority Regulatory status and indications Terizidone First marketed in Germany 1 January 1978 (15). Only quality assured supplier if Fatol, in Germany (15). However, terizidone is a scheduled medication in South Africa, regulated by the Medicines Control Council (35). Sanofi pharmaceuticals manufactures terizidone in South Africa under the name “Terivalidin” (36). United States Food and Not found Drug Administration European Medicines Not found Agency WHO List of Not found Prequalified Medications Health Canada Not found Australian Government Not found Department of Health Pharmaceuticals and Not found Medical Devices Agency (Japan) 14. Availability of pharmacopoeial standards (British Pharmacopoeia, International Pharmacopoeia, United States Pharmacopoeia, European Pharmacopeia) Drug Standard Reference (accessed 22.10.2014) Terizidone Not found in the British Pharmacopoeia, International Pharmacopoeia, United States Pharmacopoeia or European Pharmacopeia 15. Proposed (new/adapted) text that could be included in a revised WHO Model Formulary If this request is approved, it is proposed that identical modifications are made to the tabulations in the WHO Model List of Essential Medicines (18th list)(1), and the WHO Model List of Essential Medicines for Children (4th list)(2) to accommodate the new addition.
Recommended publications
  • Efficacy and Safety of World Health Organization Group 5 Drugs for Multidrug-Resistant Tuberculosis Treatment
    ERJ Express. Published on September 17, 2015 as doi: 10.1183/13993003.00649-2015 REVIEW IN PRESS | CORRECTED PROOF Efficacy and safety of World Health Organization group 5 drugs for multidrug-resistant tuberculosis treatment Nicholas Winters1,2, Guillaume Butler-Laporte1 and Dick Menzies1,2 Affiliations: 1Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, McGill University, Montreal, PQ, Canada. 2Dept of Epidemiology and Biostatistics, McGill University, Montreal, PQ, Canada. Correspondence: Dick Menzies, Montreal Chest Institute, Room K1.24, 3650 St Urbain, Montreal, PQ, Canada, H2X 2P4. E-mail: [email protected] ABSTRACT The efficacy and toxicity of several drugs now used to treat multidrug-resistant tuberculosis (MDR-TB) have not been fully evaluated. We searched three databases for studies assessing efficacy in MDR-TB or safety during prolonged treatment of any mycobacterial infections, of drugs classified by the World Health Organization as having uncertain efficacy for MDR-TB (group 5). We included 83 out of 4002 studies identified. Evidence was inadequate for meropenem, imipenem and terizidone. For MDR-TB treatment, clarithromycin had no efficacy in two studies (risk difference (RD) −0.13, 95% CI −0.40–0.14) and amoxicillin–clavulanate had no efficacy in two other studies (RD 0.07, 95% CI −0.21–0.35). The largest number of studies described prolonged use for treatment of non- tuberculous mycobacteria. Azithromycin was not associated with excess serious adverse events (SAEs). Clarithromycin was not associated with excess SAEs in eight controlled trials in HIV-infected patients (RD 0.00, 95% CI −0.02–0.02), nor in six uncontrolled studies in HIV-uninfected patients, whereas six uncontrolled studies in HIV-infected patients clarithromycin caused substantial SAEs (proportion 0.20, 95% CI 0.12–0.27).
    [Show full text]
  • Clofazimine As a Treatment for Multidrug-Resistant Tuberculosis: a Review
    Scientia Pharmaceutica Review Clofazimine as a Treatment for Multidrug-Resistant Tuberculosis: A Review Rhea Veda Nugraha 1 , Vycke Yunivita 2 , Prayudi Santoso 3, Rob E. Aarnoutse 4 and Rovina Ruslami 2,* 1 Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung 40161, Indonesia; [email protected] 2 Division of Pharmacology and Therapy, Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung 40161, Indonesia; [email protected] 3 Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran—Hasan Sadikin Hospital, Bandung 40161, Indonesia; [email protected] 4 Department of Pharmacy, Radboud University Medical Center, Radboud Institute for Health Sciences, 6255HB Nijmegen, The Netherlands; [email protected] * Correspondence: [email protected] Abstract: Multidrug-resistant tuberculosis (MDR-TB) is an infectious disease caused by Mycobac- terium tuberculosis which is resistant to at least isoniazid and rifampicin. This disease is a worldwide threat and complicates the control of tuberculosis (TB). Long treatment duration, a combination of several drugs, and the adverse effects of these drugs are the factors that play a role in the poor outcomes of MDR-TB patients. There have been many studies with repurposed drugs to improve MDR-TB outcomes, including clofazimine. Clofazimine recently moved from group 5 to group B of drugs that are used to treat MDR-TB. This drug belongs to the riminophenazine class, which has lipophilic characteristics and was previously discovered to treat TB and approved for leprosy. This review discusses the role of clofazimine as a treatment component in patients with MDR-TB, and Citation: Nugraha, R.V.; Yunivita, V.; the drug’s properties.
    [Show full text]
  • Analysis of Mutations Leading to Para-Aminosalicylic Acid Resistance in Mycobacterium Tuberculosis
    www.nature.com/scientificreports OPEN Analysis of mutations leading to para-aminosalicylic acid resistance in Mycobacterium tuberculosis Received: 9 April 2019 Bharati Pandey1, Sonam Grover2, Jagdeep Kaur1 & Abhinav Grover3 Accepted: 31 July 2019 Thymidylate synthase A (ThyA) is the key enzyme involved in the folate pathway in Mycobacterium Published: xx xx xxxx tuberculosis. Mutation of key residues of ThyA enzyme which are involved in interaction with substrate 2′-deoxyuridine-5′-monophosphate (dUMP), cofactor 5,10-methylenetetrahydrofolate (MTHF), and catalytic site have caused para-aminosalicylic acid (PAS) resistance in TB patients. Focusing on R127L, L143P, C146R, L172P, A182P, and V261G mutations, including wild-type, we performed long molecular dynamics (MD) simulations in explicit solvent to investigate the molecular principles underlying PAS resistance due to missense mutations. We found that these mutations lead to (i) extensive changes in the dUMP and MTHF binding sites, (ii) weak interaction of ThyA enzyme with dUMP and MTHF by inducing conformational changes in the structure, (iii) loss of the hydrogen bond and other atomic interactions and (iv) enhanced movement of protein atoms indicated by principal component analysis (PCA). In this study, MD simulations framework has provided considerable insight into mutation induced conformational changes in the ThyA enzyme of Mycobacterium. Antimicrobial resistance (AMR) threatens the efective treatment of tuberculosis (TB) caused by the bacteria Mycobacterium tuberculosis (Mtb) and has become a serious threat to global public health1. In 2017, there were reports of 5,58000 new TB cases with resistance to rifampicin (frst line drug), of which 82% have developed multidrug-resistant tuberculosis (MDR-TB)2. AMR has been reported to be one of the top health threats globally, so there is an urgent need to proactively address the problem by identifying new drug targets and understanding the drug resistance mechanism3,4.
    [Show full text]
  • SDC 1. Supplementary Notes to Methods Settings Groote Schuur
    Mouton JP, Njuguna C, Kramer N, Stewart A, Mehta U, Blockman M, et al. Adverse drug reactions causing admission to medical wards: a cross-sectional survey at four hospitals in South Africa. Supplemental Digital Content SDC 1. Supplementary notes to Methods Settings Groote Schuur Hospital is a 975-bed urban academic hospital situated in Cape Town, in the Western Cape province, which provides secondary and tertiary level care, serves as a referral centre for approximately half of the province’s population (2011 population: 5.8 million)1 and is associated with the University of Cape Town. At this hospital we surveyed the general medical wards during May and June 2013. We did not survey the sub-speciality wards (dermatology, neurology, cardiology, respiratory medicine and nephrology), the oncology wards, or the high care / intensive care units. Restricting the survey to general medical wards was done partly due to resource limitations but also to allow the patients at this site to be reasonably comparable to those at other sites, which did not have sub-specialist wards. In 2009, the crude inpatient mortality in the medical wards of Groote Schuur Hospital was shown to be 573/3465 patients (17%)2 and the 12-month post-discharge mortality to be 145/415 (35%).3 Edendale Hospital is a 900-bed peri-urban regional teaching hospital situated near Pietermaritzburg, in the KwaZulu-Natal province (2011 population: 10.3 million).1 It provides care to the peri-urban community and serves as a referral centre for several district hospitals in the surrounding rural area. It is located at the epicentre of the HIV, tuberculosis and multidrug resistant tuberculosis epidemics in South Africa: a post-mortem study in 2008-2009 found that 94% of decedents in the medical wards of Edendale Hospital were HIV-seropositive, 50% had culture-positive tuberculosis at the time of death and 17% of these cultures were resistant to isoniazid and rifampicin.4 At Edendale Hospital, we surveyed the medical wards over 30 days during July and August of 2013.
    [Show full text]
  • Treatment of Drug-Resistant Tuberculosis an Official ATS/CDC/ERS/IDSA Clinical Practice Guideline Payam Nahid, Sundari R
    AMERICAN THORACIC SOCIETY DOCUMENTS Treatment of Drug-Resistant Tuberculosis An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline Payam Nahid, Sundari R. Mase, Giovanni Battista Migliori, Giovanni Sotgiu, Graham H. Bothamley, Jan L. Brozek, Adithya Cattamanchi, J. Peter Cegielski, Lisa Chen, Charles L. Daley, Tracy L. Dalton, Raquel Duarte, Federica Fregonese, C. Robert Horsburgh, Jr., Faiz Ahmad Khan, Fayez Kheir, Zhiyi Lan, Alfred Lardizabal, Michael Lauzardo, Joan M. Mangan, Suzanne M. Marks, Lindsay McKenna, Dick Menzies, Carole D. Mitnick, Diana M. Nilsen, Farah Parvez, Charles A. Peloquin, Ann Raftery, H. Simon Schaaf, Neha S. Shah, Jeffrey R. Starke, John W. Wilson, Jonathan M. Wortham, Terence Chorba, and Barbara Seaworth; on behalf of the American Thoracic Society, U.S. Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Diseases Society of America THIS OFFICIAL CLINICAL PRACTICE GUIDELINE WAS APPROVED BY THE AMERICAN THORACIC SOCIETY, THE EUROPEAN RESPIRATORY SOCIETY, AND THE INFECTIOUS DISEASES SOCIETY OF AMERICA SEPTEMBER 2019, AND WAS CLEARED BY THE U.S. CENTERS FOR DISEASE CONTROL AND PREVENTION SEPTEMBER 2019 Background: The American Thoracic Society, U.S. Centers for was judged to be very low, because the data came Disease Control and Prevention, European Respiratory Society, and from observational studies with significant loss to follow-up Infectious Diseases Society of America jointly sponsored this new and imbalance in background regimens between comparator practice guideline on the treatment of drug-resistant tuberculosis groups. Good practices in the management of MDR-TB are (DR-TB). The document includes recommendations on the described. On the basis of the evidence review, a clinical strategy treatment of multidrug-resistant TB (MDR-TB) as well as tool for building a treatment regimen for MDR-TB is also isoniazid-resistant but rifampin-susceptible TB.
    [Show full text]
  • Of TB Drug Development: What's on the Horizon (For Patients with Or Without
    The ‘third wave’ of TB drug development: What’s on the horizon (for patients with or without HIV) Kelly Dooley, MD, PhD 20th International Workshop on Clinical Pharmacology of HIV, Hepatitis, Other Antivirals Noordwijk, The Netherlands 15 May 2019 D I V I S I O N O F CLINICAL PHARMACOLOGY 1 Objectives • To give you an idea of the drug development pathway for TB drugs, the history, and the pipeline • To convince you to come work in the TB field, if you are not already The Problem State-of-the-state: Global burden of TB disease: 2017 In 2014, TB surpassed HIV as the #1 infectious disease killer worldwide In 2017, 10.0M cases TB is estimated to have killed 1 in 7 of humans who have ever lived WHO Global Tuberculosis Report 2018: http://www.who.int/tb/publications/global_report/en/ Latent TB infection (LTBI) About 1 in 4 persons Chaisson and Golub, Lancet Global Health, 2017 MDR- and XDR-TB: Global Health Emergencies Multidrug-resistant TB: Mycobacterium tuberculosis resistant to isoniazid Extensively drug-resistant TB: and rifampin: 558,000 incident cases in 2017 M. tuberculosis resistant to isoniazid, rifampin, fluoroquinolones, and injectable agents Reported in 123 WHO member state countries 6 HIV and Tuberculosis Epidemiology Global Burden of Tuberculosis, 2017 Total Population HIV-Infected Persons Incidence 10.0 million 900,000 (9%) Deaths 1.3 million 300,000 (23%) WHO Report 2018 Global Tuberculosis Control7 TB Treatment: Global Scientific Agenda Area Goals Drug-sensitive TB Treatment shortening to < 3 months More options for patients
    [Show full text]
  • MDR-TB): Evidence and Perspectives
    Editorial Classification of drugs to treat multidrug-resistant tuberculosis (MDR-TB): evidence and perspectives Adrian Rendon1,2*, Simon Tiberi3*, Anna Scardigli4*, Lia D’Ambrosio5,6*, Rosella Centis5, Jose A. Caminero7, Giovanni Battista Migliori5 1Center for Research, Prevention and Treatment of Respiratory Infections, University Hospital Dr José Eleuterio Gonzalez, Monterrey, N.L., Mexico; 2Latin American Thoracic Association (ALAT); 3Division of Infection, Barts Health NHS Trust, London, UK; 4The Global Fund to Fight Aids, Tuberculosis and Malaria, Geneva, Switzerland; 5Maugeri Institute, IRCCS, Tradate, Italy; 6Public Health Consulting Group, Lugano, Switzerland; 7Pneumology Department, University Hospital of Gran Canaria “Dr. Negrin”, Las Palmas Gran Canaria, Spain *These authors contributed equally to this work. Correspondence to: Giovanni Battista Migliori. Maugeri Institute, IRCCS, Via Roncaccio 16, 21049 Tradate, Italy. Email: [email protected]. Submitted Aug 30, 2016. Accepted for publication Sep 05, 2016. doi: 10.21037/jtd.2016.10.14 View this article at: http://dx.doi.org/10.21037/jtd.2016.10.14 Multidrug-resistant (MDR) tuberculosis (TB) (defined Rationale basis of anti-TB treatment as resistance to at least isoniazid and rifampicin), has a The historical principles, derived from randomized clinical relevant epidemiological impact, with 480, 000 cases and trials (RCTs), are still valid: (I) combining different effective 190,000 deaths notified in 2014; 10% of them meet the drugs to prevent the selection of resistant mutants of M. criteria for extensively drug-resistant (XDR)-TB [MDR- tuberculosis; and (II) prolonging the treatment to sterilise the TB with additional resistance to any fluoroquinolone, infected tissues and, therefore, prevent relapse (1,9,10). and to at least one injectable second-line drugs (SLDs)] At least four drugs likely to be effective compose (capreomycin, kanamycin or amikacin) (1,2).
    [Show full text]
  • BMJ Open Is Committed to Open Peer Review. As Part of This Commitment We Make the Peer Review History of Every Article We Publish Publicly Available
    BMJ Open is committed to open peer review. As part of this commitment we make the peer review history of every article we publish publicly available. When an article is published we post the peer reviewers’ comments and the authors’ responses online. We also post the versions of the paper that were used during peer review. These are the versions that the peer review comments apply to. The versions of the paper that follow are the versions that were submitted during the peer review process. They are not the versions of record or the final published versions. They should not be cited or distributed as the published version of this manuscript. BMJ Open is an open access journal and the full, final, typeset and author-corrected version of record of the manuscript is available on our site with no access controls, subscription charges or pay-per-view fees (http://bmjopen.bmj.com). If you have any questions on BMJ Open’s open peer review process please email [email protected] BMJ Open Pediatric drug utilization in the Western Pacific region: Australia, Japan, South Korea, Hong Kong and Taiwan Journal: BMJ Open ManuscriptFor ID peerbmjopen-2019-032426 review only Article Type: Research Date Submitted by the 27-Jun-2019 Author: Complete List of Authors: Brauer, Ruth; University College London, Research Department of Practice and Policy, School of Pharmacy Wong, Ian; University College London, Research Department of Practice and Policy, School of Pharmacy; University of Hong Kong, Centre for Safe Medication Practice and Research, Department
    [Show full text]
  • Effect of Tablet Crushing on Drug Exposure in the Treatment of Multidrug-Resistant Tuberculosis
    INT J TUBERC LUNG DIS 23(10):1068–1074 Q 2019 The Union http://dx.doi.org/10.5588/ijtld.18.0775 Effect of tablet crushing on drug exposure in the treatment of multidrug-resistant tuberculosis R. Court,1 M. T. Chirehwa,1 L. Wiesner,1 N. de Vries,2 J. Harding,3 T. Gumbo,4 G. Maartens,1 H. McIlleron1 1Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, 2Brooklyn Chest Hospital, Cape Town, 3DP Marais Hospital, Cape Town, South Africa; 4Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, TX, USA SUMMARY SETTING: Treatment outcomes in multidrug-resistant compartmental analysis was used to derive the key tuberculosis (MDR-TB) are poor. Due to drug toxicity pharmacokinetic measurements. and a long treatment duration, approximately half of RESULTS: Twenty participants completed the study: 15 patients are treated successfully. Medication is often were men, and the median age was 31.5 years. There was crushed for patients who have difficulty swallowing a 42% reduction in the area under the curve AUC0–10 of whole tablets. Whether crushing tablets affects drug INH when the tablets were crushed compared with exposure in MDR-TB treatment is not known. whole tablets (geometric mean ratio 58%; 90%CI 47– OBJECTIVE AND DESIGN: We performed a sequential 73). Crushing tablets of pyrazinamide, moxifloxacin, pharmacokinetic study in patients aged .18 years on ethambutol and terizidone did not affect the bioavail- MDR-TB treatment at two hospitals in Cape Town, ability significantly. South Africa. We compared the bioavailability of CONCLUSION: We recommend that crushing of INH pyrazinamide, moxifloxacin, isoniazid (INH), ethambu- tablets in the MDR-TB treatment regimen be avoided.
    [Show full text]
  • Clinical Implications of the Global Multidrug-Resistant Tuberculosis Epidemic
    Clinical Medicine 2016 Vol 16, No 6: 565–70 HORIZONS IN MEDICINE C l i n i c a l i m p l i c a t i o n s o f t h e g l o b a l m u l t i d r u g - r e s i s t a n t tuberculosis epidemic Authors: K a r t i k K u m a r A a n d I b r a h i m A b u b a k a r B Multidrug-resistant tuberculosis (MDR TB) is a signifi cant fluoroquinolones and at least one of the second-line injectable threat to global health estimated to account for nearly half a drugs (capreomycin, kanamycin and amikacin). 2 million new cases and over 200,000 deaths in 2013. The num- Here we provide an overview of the importance of MDR TB, its ber of MDR TB cases in the UK has risen over the last 15 years, epidemiology, clinical implications, potential ways of addressing with ever more complex clinical cases and associated challeng- the disease and prospects for new diagnostics and treatment. ABSTRACT ing public health and societal implications. In this review, we provide an overview of the epidemiology of MDR TB globally E p i d e m i o l o g y and in the UK, outline the clinical management of MDR TB and summarise recent advances in diagnostics and prospects Global epidemiology of TB for new treatment. Unfortunately, data on drug resistance are limited by a number of factors, including lack of facilities for testing and the K E Y W O R D S : Multidrug-resistant tuberculosis, epidemiology, limited availability of routine surveillance that only occurs in diagnostics, treatment approximately 50% of countries.
    [Show full text]
  • Alphabetical Listing of ATC Drugs & Codes
    Alphabetical Listing of ATC drugs & codes. Introduction This file is an alphabetical listing of ATC codes as supplied to us in November 1999. It is supplied free as a service to those who care about good medicine use by mSupply support. To get an overview of the ATC system, use the “ATC categories.pdf” document also alvailable from www.msupply.org.nz Thanks to the WHO collaborating centre for Drug Statistics & Methodology, Norway, for supplying the raw data. I have intentionally supplied these files as PDFs so that they are not quite so easily manipulated and redistributed. I am told there is no copyright on the files, but it still seems polite to ask before using other people’s work, so please contact <[email protected]> for permission before asking us for text files. mSupply support also distributes mSupply software for inventory control, which has an inbuilt system for reporting on medicine usage using the ATC system You can download a full working version from www.msupply.org.nz Craig Drown, mSupply Support <[email protected]> April 2000 A (2-benzhydryloxyethyl)diethyl-methylammonium iodide A03AB16 0.3 g O 2-(4-chlorphenoxy)-ethanol D01AE06 4-dimethylaminophenol V03AB27 Abciximab B01AC13 25 mg P Absorbable gelatin sponge B02BC01 Acadesine C01EB13 Acamprosate V03AA03 2 g O Acarbose A10BF01 0.3 g O Acebutolol C07AB04 0.4 g O,P Acebutolol and thiazides C07BB04 Aceclidine S01EB08 Aceclidine, combinations S01EB58 Aceclofenac M01AB16 0.2 g O Acefylline piperazine R03DA09 Acemetacin M01AB11 Acenocoumarol B01AA07 5 mg O Acepromazine N05AA04
    [Show full text]
  • Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DIX to the HTSUS—Continued
    20558 Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DEPARMENT OF THE TREASURY Services, U.S. Customs Service, 1301 TABLE 1.ÐPHARMACEUTICAL APPEN- Constitution Avenue NW, Washington, DIX TO THE HTSUSÐContinued Customs Service D.C. 20229 at (202) 927±1060. CAS No. Pharmaceutical [T.D. 95±33] Dated: April 14, 1995. 52±78±8 ..................... NORETHANDROLONE. A. W. Tennant, 52±86±8 ..................... HALOPERIDOL. Pharmaceutical Tables 1 and 3 of the Director, Office of Laboratories and Scientific 52±88±0 ..................... ATROPINE METHONITRATE. HTSUS 52±90±4 ..................... CYSTEINE. Services. 53±03±2 ..................... PREDNISONE. 53±06±5 ..................... CORTISONE. AGENCY: Customs Service, Department TABLE 1.ÐPHARMACEUTICAL 53±10±1 ..................... HYDROXYDIONE SODIUM SUCCI- of the Treasury. NATE. APPENDIX TO THE HTSUS 53±16±7 ..................... ESTRONE. ACTION: Listing of the products found in 53±18±9 ..................... BIETASERPINE. Table 1 and Table 3 of the CAS No. Pharmaceutical 53±19±0 ..................... MITOTANE. 53±31±6 ..................... MEDIBAZINE. Pharmaceutical Appendix to the N/A ............................. ACTAGARDIN. 53±33±8 ..................... PARAMETHASONE. Harmonized Tariff Schedule of the N/A ............................. ARDACIN. 53±34±9 ..................... FLUPREDNISOLONE. N/A ............................. BICIROMAB. 53±39±4 ..................... OXANDROLONE. United States of America in Chemical N/A ............................. CELUCLORAL. 53±43±0
    [Show full text]