DOCSLIB.ORG

Telaprevir for HIV/Hepatitis C Virus–Coinfected Patients Failing

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Telaprevir for HIV/Hepatitis C Virus–Coinfected Patients Failing HIV/AIDS MAJOR ARTICLE Telaprevir for HIV/Hepatitis C Virus–Coinfected Patients Failing Treatment With Pegylated Interferon/Ribavirin (ANRS HC26 TelapreVIH): An Open-Label, Single-Arm, Phase 2 Trial Downloaded from https://academic.oup.com/cid/article/59/12/1768/2895305 by guest on 01 October 2021 Laurent Cotte,1 Joséphine Braun,2 Caroline Lascoux-Combe,3 Corine Vincent,2 Marc-Antoine Valantin,4 Philippe Sogni,5 Karine Lacombe,6 Didier Neau,7 Hugues Aumaitre,8 Dominique Batisse,9 Pierre de Truchis,10 Anne Gervais,11 Christian Michelet,12 Philippe Morlat,13 Daniel Vittecoq,14 Isabelle Rosa,15 Inga Bertucci,16 Stéphane Chevaliez,17 Jean-Pierre Aboulker,2 and Jean-Michel Molina3; for the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) HC26 Study Groupa 1Hospices Civils de Lyon, Croix-Rousse Hospital, and INSERM U1052, 2INSERM SC10-US019, Villejuif, 3Assistance Publique–Hôpitaux de Paris (AP-HP), Saint-Louis Hospital, University of Paris VII Denis Diderot, and Sorbonne Paris-Cité, INSERM U941, 4AP-HP, Pitié-Salpêtrière Hospital, and UMR-S 943, INSERM, 5AP-HP, Cochin Hospital and Paris Descartes University, INSERM U-1016, 6AP-HP, Saint-Antoine Hospital, Sorbonne Universités, UPMC University Paris 06, UMR-S1136, 7Pellegrin University Hospital, Bordeaux, 8Saint-Jean Hospital, Perpignan, 9AP-HP, Georges Pompidou European Hospital, Paris, 10AP-HP, Raymond Poincaré Hospital, Garches, 11AP-HP, Bichat-Claude Bernard Hospital, Paris, 12Pontchaillou University Hospital, Rennes, 13Saint-André University Hospital, Bordeaux, 14AP-HP, Bicètre Hospital, Le Kremlin-Bicètre, 15Créteil Hospital, 16French National Agency for Research on AIDS and Viral Hepatitis, Paris, and 17AP-HP, Henri Mondor Hospital, Créteil, France (See the Editorial Commentary by Rockstroh on pages 1777–8.) Background. Retreatment with pegylated interferon (peg-IFN) and ribavirin (RBV) results in poor sustained virological response (SVR) rates in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)–coinfected pa- tients. There are limited data regarding the use of telaprevir plus peg-IFN/RBV in this population. Methods. HIV type 1–infected patients who previously failed ≥12 weeks of peg-IFN/RBV for HCV genotype 1 coinfection were enrolled in a single-arm, phase 2 trial. Patients with cirrhosis and previous null response were exclud- ed. Authorized antiretrovirals were tenofovir, emtricitabine, efavirenz, atazanavir, and raltegravir. All patients received peg-IFN alfa-2a (180 µg/week) plus RBV (1000–1200 mg/day) for 4 weeks, followed by telaprevir (750 mg or 1125 mg every 8 hours with efavirenz) plus peg-IFN/RBV for 12 weeks and peg-IFN/RBV for 32–56 weeks according to viro- logical response at week 8. The primary endpoint was the SVR rate at 24 weeks after the end of treatment (SVR24). fi – Results Sixty-nine patients started treatment; SVR24 was achieved in 55 (80% [95% con dence interval, 68% fl fi IL28B 88%). SVR24 was not in uenced by baseline brosis stage, genotype, antiretroviral regimen, HCV subtype, CD4 cell count, previous response to HCV treatment, HCV RNA level, or HCV RNA decline at week 4. HCV treatment was discontinued for adverse events (AEs) in 20% of patients, including cutaneous (4%), psychiatric (4%), hematolog- ical (6%), and other AEs (6%). Peg-IFN or RBV dose reduction was required in 23% and 43% of patients, respectively. Seventy percent of patients required erythropoietin, blood transfusions, or RBV dose reduction for anemia. Two pa- tients died during the study. No HIV breakthrough was observed. Conclusions. Despite a high discontinuation rate related to toxicity, a substantial proportion of treatment-experi- enced HIV-coinfected patients achieved SVR24 with a telaprevir-based regimen. Clinical Trials Registration. NCT01332955. Keywords. HIV/HCV coinfection; HCV retreatment; telaprevir; direct acting agent. Correspondence: Laurent Cotte, MD, Department of Infectious Diseases and Received 8 May 2014; accepted 22 July 2014; electronically published 18 August Tropical Medicine, Croix-Rousse Hospital, 69317 Lyon Cedex 04, France (laurent. 2014. [email protected]). Presented in part: 20th Conference on Retroviruses and Opportunistic Infections, Clinical Infectious Diseases® 2014;59(12):1768–76 Atlanta, Georgia, 2013; 64th Liver Meeting, Washington, D.C., 2013; and 21st © The Author 2014. Published by Oxford University Press on behalf of the Infectious Conference on Retroviruses and Opportunistic Infections, Boston, Massachusetts, Diseases Society of America. All rights reserved. For Permissions, please e-mail: 2014. [email protected]. aThe ANRS HC26 study group members are listed in the Appendix. DOI: 10.1093/cid/ciu659 1768 • CID 2014:59 (15 December) • HIV/AIDS Worldwide, 20%–30% of patients with human immunodefi- criteria were hepatitis B virus coinfection; HIV type 2 infection; ciency virus (HIV) are coinfected with hepatitis C virus active opportunistic infection; active malignancy; organ trans- (HCV) [1, 2]. The advent of combination antiretroviral therapy plant; Child-Pugh score B or C; severe psychiatric, cardiac, or (cART) has dramatically decreased HIV-related mortality, but pulmonary disease; severe hemoglobinopathy; uncontrolled seri- liver-related mortality is still increasing [3, 4]. ous comorbidity; or history of decompensated cirrhosis. The standard treatment in HCV-monoinfected patients used Authorized antiretrovirals were defined according to known to be a combination of pegylated interferon (peg-IFN) plus interactions with telaprevir [25, 26] and associated a tenofovir/ ribavirin (RBV) for 48 weeks in patients infected with HCV emtricitabine backbone with either efavirenz, raltegravir, or genotype 1 or 4, allowing a sustained virological response (SVR) ritonavir-boosted atazanavir, or any combination of these in about 50% of cases [5–7]. In HIV/HCV-coinfected patients, drugs. response rates were much lower [8–11], and retreatment of Previous HCV virological failure was defined by the persis- genotype 1 patients who had previously failed a course of tence of a detectable HCV RNA level following treatment, with peg-IFN/RBV led to an SVR rate of about 10% [12–15]. the same genotype. The virological response to treatment was Downloaded from https://academic.oup.com/cid/article/59/12/1768/2895305 by guest on 01 October 2021 Triple therapy based on peg-IFN/RBV and NS3/4A protease classified as relapse (ie, patient with undetectable HCV RNA at inhibitors (boceprevir or telaprevir) became the new standard of the end of treatment and detectable HCV RNA thereafter), care in 2011 [16–19]. For telaprevir-based triple therapy [20], breakthrough (ie, patient with undetectable HCV RNA at least SVR is achieved in about 75% of treatment-naive patients once under treatment, becoming detectable thereafter), and non- monoinfected with HCV [17, 21] and 71% of previous relapsers responder including partial responder (ie, >2 log10 HCV RNA or partial nonresponders [22]. In addition to common side decline at week 12 and still detectable HCV RNA at week 24) fl effects associated with peg-IFN/RBV such as asthenia, in uen- and null responder (ie, <2 log10 HCV RNA decline at week 12). za-like illness, depression, anemia, and pruritus [5–7], an in- Fibrosis stage had to be documented by a liver biopsy within creased rate of anemia and rashes has been described with the past 3 years. Patients with a previous liver biopsy exhibiting telaprevir-based treatment [23]. cirrhosis lesions (ie, METAVIR score F4) were included without In HIV/HCV genotype 1–coinfected patients who were a new biopsy. Null responders without cirrhosis were limited to HCV treatment naive, an SVR of 74% has been reported with a maximum of 30% of all included patients. Patients with both telaprevir-based treatment [24]. No prospective trial has cur- cirrhosis and previous null response were not included. rently studied the effect of telaprevir-based regimens in HIV/ The study protocol, its amendments, and informed consent HCV-coinfected patients who had failed a previous treatment. documents were approved by the French Regulatory Authority The objective of the present study was to estimate the efficacy and and by the local ethics committee. The study was performed in safety of a 12-week treatment with telaprevir combined with accordance with the International Conference on Harmonisa- peg-IFN/RBV for a total of 48 or 72 weeks in HIV/HCV geno- tion Good Clinical Practice guidelines and the Declaration of type 1–coinfected patients who had failed a previous treatment. Helsinki. All patients provided written informed consent. METHODS Procedures All patients received the same treatment regimen. Treatment Study Design and Participants started with a 4-week lead-in phase with peg-IFN alfa-2a and The French National Agency for Research on AIDS and viral RBV, followed by 12 weeks of triple therapy with telaprevir/ hepatitis (ANRS) HC26 TelapreVIH study was a single-arm, peg-IFN/RBV, and by a double-therapy phase with peg-IFN/ open-label, phase 2 clinical trial. Patients were recruited from RBV. The total duration of treatment was determined by the 23 tertiary care centers from May to December 2011. Eligible pa- rapid virological response (RVR) 4 weeks after the introduction tients were aged ≥18 years, infected with HIV-1 and HCV geno- of telaprevir—that is, at week 8 (RVR8). A complete RVR8 was fi type 1, and had previously failed a treatment of at least 12 weeks de ned as HCV RNA load <15 IU/mL and a partial RVR8 as with peg-IFN alfa-2a ≥135 µg/week or peg-IFN alfa-2b ≥1.0 µg/ HCV RNA load between 15 and 1000 IU/mL at week 8. For pa- ≥ kg/week and RBV 600 mg/day. Other inclusion criteria includ- tients with a complete RVR8, the total duration of treatment was ≥ ≤ ed body weight 40 kg and 125 kg, stable cART for >3 months, 48 weeks and for patients with a partial RVR8,thepeg-IFN/ CD4 count >200 cells/µL and CD4 percentage >15%, HIV RNA RBV phase was extended, for a total duration of 72 weeks.
Load more

Recommended publications
  • Telaprevir (Incivek)
    © Hepatitis C Online PDF created September 25, 2021, 4:19 pm Telaprevir (Incivek) Discontinued. This treatment has been discontinued. Table of Contents Telaprevir Incivek Summary Drug Summary Adverse Effects Class and Mechanism Manufacturer for United States FDA Status Indications Dosing Clinical Use Cost and Medication Access Resistance Key Drug Interactions Full Prescribing Information Figures Drug Summary Although telaprevir was a promising direct-acting antiviral agent that had impact in the hepatitis C treatment field during 2011 to 2013, it was subsequently replaced by newer direct-acting antiviral agents that were more effective, better tolerated, and more convenient. Based on the dwindling role of telaprevir after newer direct-acting antiviral agents were approved, Vertex pharmaceuticals discontinued the sales and distribution of telaprevir in the United States in October 2014. Telaprevir does have some current importance since persons who previously failed a telaprevir-based regimen may have developed resistant associated variants, which could potentially impact subsequent therapy. Adverse Effects The most significant adverse effects reported in the main registration trials and in post-marketing experience were rash, anorectal complaints, and anemia. When comparing triple therapy of telaprevir, peginterferon, and ribavirin with dual therapy of peginterferon and ribavirin alone significant differences were noted with rash (56% versus 34%), anemia (36% versus 17%), and anorectal complaints that include anorectal discomfort, anal pruritus, and hemorrhoids (29% versus 7%). In most cases, the rash that develops is eczematous or maculopapular in character and mild to moderate in severity; the rash is typically manageable with good skin care and topical emollients or corticosteroids. In some instances, however, telaprevir has caused serious skin Page 1/5 rashes, including Steven's Johnson Syndrome (SJS), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), and Toxic Epidermal Necrolysis (TEN).
    [Show full text]
  • The Legally Binding Text Is the Original French Version TRANSPARENCY
    The legally binding text is the original French version TRANSPARENCY COMMITTEE OPINION 14 December 2011 INCIVO 375 mg, film-coated tablet B/4 bottles of 42 tablets (CIP code: 217 378-5) B/1 bottle of 42 tablets (CIP code: 219 249-8) Applicant: JANSSEN-CILAG telaprevir ATC Code: J05AE11 (protease inhibitor) List I Hospital prescription restricted to gastroenterology, hepatology, internal medicine or infectiology specialists. Date of Marketing Authorisation (centralised European procedure): Box of 4 bottles: 19/09/2011 Box of 1 bottle: 13/10/2011 Reason for request: Inclusion on the list of medicines refundable by National Health Insurance and on the list of medicines approved for hospital use. Medical, Economic and Public Health Assessment Division 1/22 1. CHARACTERISTICS OF THE MEDICINAL PRODUCT 1.1. Active ingredient telaprevir 1.2. Background This is an NS3/4A protease inhibitor of the genotype 1 hepatitis C virus. 1.3. Indication “INCIVO, in combination with peginterferon alfa and ribavirin, is indicated for the treatment of genotype 1 chronic hepatitis C in adult patients with compensated liver disease (including cirrhosis): - who are treatment-naive; - who have previously been treated with interferon alfa (pegylated or non-pegylated) alone or in combination with ribavirin, including relapsers, partial responders and null responders (see sections 4.4 and 5.1 of the SPC).” 1.4. Dosage “Treatment with INCIVO must be initiated and monitored by a physician experienced in the management of chronic hepatitis C. INCIVO, 750 mg dose of INCIVO (two 375 mg film-coated tablets) should be taken orally every 8 hours with food (the total daily dose is 6 tablets (2,250 mg)).
    [Show full text]
  • Caracterización Molecular Del Perfil De Resistencias Del Virus De La
    ADVERTIMENT. Lʼaccés als continguts dʼaquesta tesi queda condicionat a lʼacceptació de les condicions dʼús establertes per la següent llicència Creative Commons: http://cat.creativecommons.org/?page_id=184 ADVERTENCIA. El acceso a los contenidos de esta tesis queda condicionado a la aceptación de las condiciones de uso establecidas por la siguiente licencia Creative Commons: http://es.creativecommons.org/blog/licencias/ WARNING. The access to the contents of this doctoral thesis it is limited to the acceptance of the use conditions set by the following Creative Commons license: https://creativecommons.org/licenses/?lang=en Programa de doctorado en Medicina Departamento de Medicina Facultad de Medicina Universidad Autónoma de Barcelona TESIS DOCTORAL Caracterización molecular del perfil de resistencias del virus de la hepatitis C después del fallo terapéutico a antivirales de acción directa mediante secuenciación masiva Tesis para optar al grado de doctor de Qian Chen Directores de la Tesis Dr. Josep Quer Sivila Dra. Celia Perales Viejo Dr. Josep Gregori i Font Laboratorio de Enfermedades Hepáticas - Hepatitis Víricas Vall d’Hebron Institut de Recerca (VHIR) Barcelona, 2018 ABREVIACIONES Abreviaciones ADN: Ácido desoxirribonucleico AK: Adenosina quinasa ALT: Alanina aminotransferasa ARN: Ácido ribonucleico ASV: Asunaprevir BOC: Boceprevir CCD: Charge Coupled Device CLDN1: Claudina-1 CHC: Carcinoma hepatocelular DAA: Antiviral de acción directa DC-SIGN: Dendritic cell-specific ICAM-3 grabbing non-integrin DCV: Daclatasvir DSV: Dasabuvir
    [Show full text]
  • PASS Information
    PASS Information Title Cilostazol drug utilisation study Protocol version Version 2.3 identifier Date of last version of 5 November 2015 protocol EU PAS register number ENCEPP/SDPP/3596 http://www.encepp.eu/encepp/viewResource.htm?id=10426 Accessed 5 November 2015 Active substance Cilostazol, ATC code B01AC23, Platelet aggregation inhibitors excluding heparin Medicinal product Pletal, Ekistol Product reference UK/H/0291/001 and 002 Procedure number EMEA/H/A-31/1306 Marketing authorisation Otsuka Pharmaceutical Europe Ltd. holder(s) (MAH) Lacer S.A. Joint PASS No Research question and This study protocol was developed in the context of the European objectives Medicines Agency (EMA) referral (article 31 of Council Directive 2001/83/EC) on the risks and benefits of the use of cilostazol. The study objectives are to characterise patients using cilostazol according to demographics, comorbidity, comedications, and duration of treatment. In addition, the study will describe the dosing of cilostazol, the prescribing physician specialties, and the potential off-label prescribing. Country(-ies) of study Spain, United Kingdom, Germany, Sweden Author Jordi Castellsague, MD, MPH; Cristina Varas-Lorenzo, MD, MPH, PhD; Susana Perez-Gutthann, MD, MPH, PhD RTI Health Solutions Trav. Gracia 56 Atico 1 08006 Barcelona, Spain Telephone: +34.93.241.7766 Fax: +34.93.414.2610 E-mail: [email protected] CONFIDENTIAL 1 of 65 Marketing Authorisation Holder(s) Marketing authorisation Otsuka Pharmaceutical Europe Ltd. holder(s) Gallions Wexham Springs Framewood Road Wexham SL3 6PJ, UK Lacer S.A. Sardenya 350 08025 Barcelona Spain MAH contact person Dr Marco Avila Regional Vice President, Medical Europe Otsuka Pharmaceutical Europe Ltd EU QPPV Dr Achint Kumar Otsuka Europe Development and Commercialisation Limited (OEDC) Head of Medical Dr Sanjay Kapoor Compliance-Europe Otsuka Pharmaceutical Europe Ltd.
    [Show full text]
  • Medicinal Product No Longer Authorised
    Assessment report INCIVO telaprevir Procedure No.: EMEA/H/C/002313/ Note Assessment report as adopted by the CHMP with all information of a commercially confidential nature deleted. Medicinal product no longer authorised 7 Westferry Circus ● Canary Wharf ● London E14 4HB ● United Kingdom Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7418 8613 E-mail [email protected] Website www.ema.europaeu An agency of the European Union © European Medicines Agency, 2011. Reproduction is authorised provided the source is acknowledged. 21 July 2011 EMA/CHMP/475470/2011 Committee for Medicinal Products for Human Use (CHMP) CHMP assessment report INCIVO International non-proprietary name: telaprevir authorised Procedure No. EMEA/H/C/002313 longer no product Medicinal 7 Westferry Circus ● Canary Wharf ● London E14 4HB ● United Kingdom Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7418 8613 E-mail [email protected] Website www.ema.europaeu An agency of the European Union CHMP assessment report Page 2/109 Product information Name of the medicinal product: INCIVO Applicant: Janssen-Cilag International N.V. Turnhoutseweg 30 BE-2340 Beerse Belgium Active substance: telaprevir International Nonproprietary Name/Common Name: telaprevir Pharmaco-therapeutic group Protease inhibitors authorised (ATC Code): (J05AE) INCIVO, in combination with peginterferon alfa and ribavirin, is indicated for the treatment of genotype Therapeutic indication(s): 1 chronic hepatitis C in adult patients with compensated liver disease (including cirrhosis): - who are treatment-naïve; - who have previously been treated with interferonlonger alfa (pegylated or non-pegylated) alone or in combination with ribavirin, including relapsers, partial responders and null responders (see sections 4.4 and 5.1).
    [Show full text]
  • PASS Information Title Cilostazol Drug Utilisation Study
    PASS Information Title Cilostazol drug utilisation study Protocol version Version 2 identifier Date of last version of February 28, 2013 protocol EU PAS register number Registration is planned prior to study initiation once the protocol is final and has received regulatory endorsement by the Committee for Medicinal Products for Human Use (CHMP) Active substance Cilostazol, ATC code B01AC23, Platelet aggregation inhibitors excluding heparin Medicinal product Pletal, Ekistol Product reference UK/H/0291/001 and 002 Procedure number EMEA/H/A-31/1306 Marketing authorisation Otsuka Pharmaceutical Europe Ltd. holder(s) (MAH) Lacer S.A. Joint PASS No Research question and This study protocol was developed in the context of the European objectives Medicines Agency (EMA) referral (article 31 of Council Directive 2001/83/EC) on the risks and benefits of the use of cilostazol. The study objectives are to characterise patients using cilostazol according to demographics, comorbidity, comedications, and duration of treatment. In addition, the study will describe the dosing of cilostazol, the prescribing physician specialties, and the potential off-label prescribing. Country(-ies) of study Spain, United Kingdom, Germany, Sweden Author Jordi Castellsague, MD, MPH; Cristina Varas-Lorenzo, MD, MPH, PhD; Susana Perez-Gutthann, MD, MPH, PhD RTI Health Solutions Trav. Gracia 56 Atico 1 08006 Barcelona, Spain Telephone: +34.93.241.7766 Fax: +34.93.414.2610 E-mail: [email protected] CONFIDENTIAL 1 of 56 Marketing Authorisation Holder(s) Marketing authorisation
    [Show full text]
  • Inhibitor Development Against P7 Channel in Hepatitis C Virus
    molecules Article Inhibitor Development against p7 Channel in Hepatitis C Virus Shukun Wei 1,2,†, Xiaoyou Hu 2,3,†, Lingyu Du 1, Linlin Zhao 1,4, Hongjuan Xue 5, Chaolun Liu 6, James J. Chou 4, Jin Zhong 2,3,6, Yimin Tong 3,*, Shuqing Wang 7,* and Bo OuYang 1,2,* 1 State Key Laboratory of Molecular Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 333 Haike Road, Shanghai 201203, China; [email protected] (S.W.); [email protected] (L.D.); [email protected] (L.Z.) 2 University of Chinese Academy of Sciences, Beijing 100049, China; [email protected] (X.H.); [email protected] (J.Z.) 3 CAS Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China 4 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; [email protected] 5 National Facility for Protein Science in Shanghai, ZhangJiang Lab, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China; [email protected] 6 ShanghaiTech University, Shanghai 201210, China; [email protected] 7 School of Pharmacy, Tianjin Medical University, Tianjin 300070, China * Correspondence: [email protected] (Y.T.); [email protected] (S.W.); [email protected] (B.O.) † This authors contributed equally. Abstract: Hepatitis C Virus (HCV) is the key cause of chronic and severe liver diseases. The recent direct-acting antiviral agents have shown the clinical success on HCV-related diseases, but the rapid HCV mutations of the virus highlight the sustaining necessity to develop new drugs.
    [Show full text]
  • Symmetrel (Amantadine)
    An#virals Lecture 20 Biology W3310/4310 Virology Spring 2015 You can’t go back and you can’t stand s0ll. If the thunder don’t get you, then the lightning will. JERRY GARCIA The Wheel (lyrics by Robert Hunter) Vaccines can prevent viral disease • But they Have modest or no therapeuMc effect if an individual is already infected (excepMon?) • Our second arm of anMviral defense is anMvirals • Can stop infecMon once it Has started Despite 50 years of research, our arsenal of an#viral drugs remains dangerously small Only about 100 an0viral drugs are available on the US market Most against HIV, HCV, herpesviruses - Persistent infecons Example of approved Target Virus compound Attachment HIV Maraviroc Uncoating Influenza A Amantadine, rimantadine Acyclovir, valacyclovir, DNA polymerase Herpesviruses cidofovir Reverse transcriptase HIV Zidovudine, nevirapine HIV Saquinavir, ritonavir Viral protease HCV Telaprevir, boceprevir Neuraminidase Influenza A and B Zanamavir, oseltamivir Why are there so few anviral drugs? • Compounds interfering with virus growth can adversely affect the Host cell - Side effects are common (unacceptable) - Every step in viral life cycle engages host funcons • Some medically important viruses can’t be propagated, Have no animal model, or are dangerous - HBV, HPV, norovirus - Smallpox - Ebola, Lassa An unappreciated third reason may be the most important • A compound must block virus replicaMon completely! It must be potent • Many standard pHarmaceuMcals can be effecMve if enZyme acMvity is parMally blocked • ParMal inHibiMon
    [Show full text]
  • Usage of Antivirals and the Occurrence of Antiviral Resistance in Norway 2018
    REPORT 2019 Usage of Antivirals and the Occurrence of Antiviral Resistance in Norway 2018 RAVN Resistensovervåking av virus i Norge Resistance against Antivirals in Norway Usage of Antivirals and the Occurrence of Antiviral resistance in Norway 2018 RAVN Resistensovervåkning av virus i Norge Resistance against antivirals in Norway 2 Published by the Norwegian Institute of Public Health Division of Infection Control and Environmental Health Department for Infectious Disease registries October 2019 Title: Usage of Antivirals and the Occurrence of Antiviral Resistance in Norway 2018. RAVN Ordering: The report can be downloaded as a pdf at www.fhi.no Graphic design cover: Fete Typer ISBN nr: 978-82-8406-032-3 Emneord (MeSH): Antiviral resistance Any usage of data from this report should include a specific reference to RAVN. Suggested citation: RAVN. Usage of Antivirals and the Occurrence of Antiviral Resistance in Norway 2018. Norwegian Institute of Public Health, Oslo 2019 Resistance against antivirals in Norway • Norwegian Institute of Public Health 3 Table of contents Introduction _________________________________________________________________________ 4 Contributors and participants __________________________________________________________ 5 Sammendrag ________________________________________________________________________ 6 Summary ___________________________________________________________________________ 8 1 Antivirals and development of drug resistance ______________________________________ 10 2 The usage of antivirals in Norway
    [Show full text]
  • Estonian Statistics on Medicines 2013 1/44
    Estonian Statistics on Medicines 2013 DDD/1000/ ATC code ATC group / INN (rout of admin.) Quantity sold Unit DDD Unit day A ALIMENTARY TRACT AND METABOLISM 146,8152 A01 STOMATOLOGICAL PREPARATIONS 0,0760 A01A STOMATOLOGICAL PREPARATIONS 0,0760 A01AB Antiinfectives and antiseptics for local oral treatment 0,0760 A01AB09 Miconazole(O) 7139,2 g 0,2 g 0,0760 A01AB12 Hexetidine(O) 1541120 ml A01AB81 Neomycin+Benzocaine(C) 23900 pieces A01AC Corticosteroids for local oral treatment A01AC81 Dexamethasone+Thymol(dental) 2639 ml A01AD Other agents for local oral treatment A01AD80 Lidocaine+Cetylpyridinium chloride(gingival) 179340 g A01AD81 Lidocaine+Cetrimide(O) 23565 g A01AD82 Choline salicylate(O) 824240 pieces A01AD83 Lidocaine+Chamomille extract(O) 317140 g A01AD86 Lidocaine+Eugenol(gingival) 1128 g A02 DRUGS FOR ACID RELATED DISORDERS 35,6598 A02A ANTACIDS 0,9596 Combinations and complexes of aluminium, calcium and A02AD 0,9596 magnesium compounds A02AD81 Aluminium hydroxide+Magnesium hydroxide(O) 591680 pieces 10 pieces 0,1261 A02AD81 Aluminium hydroxide+Magnesium hydroxide(O) 1998558 ml 50 ml 0,0852 A02AD82 Aluminium aminoacetate+Magnesium oxide(O) 463540 pieces 10 pieces 0,0988 A02AD83 Calcium carbonate+Magnesium carbonate(O) 3049560 pieces 10 pieces 0,6497 A02AF Antacids with antiflatulents Aluminium hydroxide+Magnesium A02AF80 1000790 ml hydroxide+Simeticone(O) DRUGS FOR PEPTIC ULCER AND GASTRO- A02B 34,7001 OESOPHAGEAL REFLUX DISEASE (GORD) A02BA H2-receptor antagonists 3,5364 A02BA02 Ranitidine(O) 494352,3 g 0,3 g 3,5106 A02BA02 Ranitidine(P)
    [Show full text]
  • New Agents for the Treatment of Hepatitis C Virus – Focus on Telaprevir
    Virus Adaptation and Treatment Dovepress open access to scientific and medical research Open Access Full Text Article REVIEW New agents for the treatment of hepatitis C virus – focus on telaprevir AJ Thompson1–3 Abstract: Antiviral therapy for hepatitis C virus (HCV) is rapidly evolving with the advent of K Patel3 direct-acting antiviral agents. Telaprevir is a first-generation linear ketoamide inhibitor of HCV NS3 protease. Approved in 2011 as standard-of-care for the treatment of patients chronically 1Department of Gastroenterology, St Vincent’s Hospital, University of infected with HCV genotype 1, telaprevir represents a major therapeutic advance. Used in com- Melbourne, 2Victorian Infectious bination with PEGylated interferon-alfa and ribavirin, telaprevir-based regimens cured . 75% Diseases Reference Laboratory, North Melbourne, Victoria, Australia; of treatment-naïve patients in the Phase III registration studies. Telaprevir is also effective for 3Duke Clinical Research Institute patients who have previously failed interferon-based therapy. Telaprevir presents a number of new and Department of Gastroenterology, challenges for clinicians, including a more demanding dosing schedule, telaprevir-specific adverse Duke University Medical Center, Durham, NC, USA events, potential for drug–drug interactions, and selection of drug-resistant HCV variants. Keywords: telaprevir, HCV, NS3, protease inhibitor, resistance Introduction There are up to 170 million individuals chronically infected with hepatitis C virus (HCV) worldwide, all of whom are at risk of the long-term complications of cirrhosis, liver failure, and hepatocellular carcinoma.1 Chronic HCV infection is currently the leading indication for liver transplantation in the Western world. Furthermore, without intervention, the burden of disease secondary to HCV infection is projected to increase over the coming decades as the HCV population ages.
    [Show full text]
  • Simeprevir (Olysio)
    © Hepatitis C Online PDF created September 28, 2021, 12:52 pm Simeprevir (Olysio) Discontinued. This treatment has been discontinued. Table of Contents Simeprevir Olysio Summary Drug Summary Adverse Effects Class and Mechanism Manufacturer for United States FDA Status Indications Dosing Clinical Use Cost and Medication Access Resistance Key Drug Interactions Full Prescribing Information Figures Drug Summary When first introduced, simeprevir provided an excellent alternative to the older first-generation NS3/4A protease inhibitors (boceprevir and telaprevir) for the treatment of patients with genotype 1 HCV. Simeprevir is convenient (once-daily dosing), well-tolerated, and has less extensive drug-drug interactions than the first- generation protease inhibitors. Simeprevir is now infrequently used for the treatment of hepatitis C due to the availability of more effective and better tolerated direct-activing antiviral agents. Adverse Effects The most common adverse effects attributable to simeprevir are rash (including a potentially serious photosensitivity reaction), pruritus, and nausea. The photosensitivity reaction that can occur with simeprevir most often has an onset during the first 4 weeks of therapy, but can develop at any time on treatment (Figure 3). Patients taking simeprevir should limit sun exposure, use protective sun exposure measures, and avoid use of any tanning device. If a photosensitivity rash does occur while taking simeprevir, discontinuation of simeprevir should be considered and the patient should have close monitoring until the rash has resolved. Page 1/6 Rash not related to photosensitivity can also occur and similar to the photosensitivity rash most often develops during the first 4 weeks of therapy. Simeprevir contains a sulfonamide moiety, but insufficient data exist to know the risk of taking simeprevir in persons with a prior "sulfa allergy".
    [Show full text]