DOCSLIB.ORG

VIEKIRA XR Safely and Effectively

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
VIEKIRA XR Safely and Effectively HIGHLIGHTS OF PRESCRIBING INFORMATION CONTRAINDICATIONS These highlights do not include all the information needed to use • Patients with moderate to severe hepatic impairment. (4, 5.1, 8.6, 12.3) VIEKIRA XR safely and effectively. See full prescribing information for • If VIEKIRA XR is administered with ribavirin, the contraindications to VIEKIRA XR. ribavirin also apply to this combination regimen. (4) • Co-administration with drugs that are: highly dependent on CYP3A for VIEKIRA XR (dasabuvir, ombitasvir, paritaprevir, and ritonavir) clearance; moderate or strong inducers of CYP3A or strong inducers of extended-release tablets, for oral use CYP2C8; and strong inhibitors of CYP2C8. (4) Initial U.S. Approval: 2014 • Known hypersensitivity to ritonavir (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome). (4) INDICATIONS AND USAGE VIEKIRA XR includes dasabuvir, a hepatitis C virus non-nucleoside NS5B WARNINGS AND PRECAUTIONS palm polymerase inhibitor, ombitasvir, a hepatitis C virus NS5A inhibitor, • Hepatic Decompensation and Hepatic Failure in Patient with Cirrhosis: paritaprevir, a hepatitis C virus NS3/4A protease inhibitor, and ritonavir, a Hepatic decompensation and hepatic failure, including liver transplantation CYP3A inhibitor and is indicated for the treatment of adult patients with or fatal outcomes, have been reported mostly in patients with advanced chronic hepatitis C virus (HCV): cirrhosis. Monitor for clinical signs and symptoms of hepatic • genotype 1b infection without cirrhosis or with compensated cirrhosis decompensation. (5.1) • genotype 1a infection without cirrhosis or with compensated cirrhosis for • ALT Elevations: Discontinue ethinyl estradiol-containing medications prior use in combination with ribavirin. (1) to starting VIEKIRA XR (alternative contraceptive methods are recommended). Perform hepatic laboratory testing on all patients during the DOSAGE AND ADMINISTRATION first 4 weeks of treatment. For ALT elevations on VIEKIRA XR, monitor Testing Prior to Initiation - Assess for laboratory and clinical evidence of closely and follow recommendations in full prescribing information. (5.2) hepatic decompensation. (2.1) • Risks Associated With Ribavirin Combination Treatment: If VIEKIRA XR Recommended dosage: Three tablets taken once daily. VIEKIRA XR must be is administered with ribavirin, the warnings and precautions for ribavirin taken with a meal because administration under fasting conditions may result also apply to this combination regimen. (5.3) in reduced virologic response and possible development of resistance. (2.2) • Drug Interactions: The concomitant use of VIEKIRA XR and certain other drugs may result in known or potentially significant drug interactions, some Treatment Regimen and Duration by Patient Population of which may lead to loss of therapeutic effect of VIEKIRA XR. (5.4) Patient Population Treatment* Duration Genotype 1a, ADVERSE REACTIONS VIEKIRA XR + ribavirin 12 weeks without cirrhosis In subjects receiving the combination of dasabuvir with ombitasvir, paritaprevir, ritonavir with ribavirin, the most commonly reported adverse Genotype 1a, VIEKIRA XR + ribavirin 24 weeks** reactions (greater than 10% of subjects) were fatigue, nausea, pruritus, other with compensated cirrhosis skin reactions, insomnia and asthenia. In subjects receiving the combination of Genotype 1b, dasabuvir with ombitasvir, paritaprevir, ritonavir without ribavirin, the most with or without compensated VIEKIRA XR 12 weeks commonly reported adverse reactions (greater than or equal to 5% of subjects) cirrhosis were nausea, pruritus and insomnia. (6.1) *Note: Follow the genotype 1a dosing recommendations in patients with an To report SUSPECTED ADVERSE REACTIONS, contact AbbVie Inc. unknown genotype 1 subtype or with mixed genotype 1 infection. at 1-800-633-9110 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. **VIEKIRA XR administered with ribavirin for 12 weeks may be considered for some patients based on prior treatment history [See Clinical Studies DRUG INTERACTIONS (14.3)]. Co-administration of VIEKIRA XR can alter the plasma concentrations of some drugs and some drugs may alter the plasma concentrations of VIEKIRA • HCV/HIV-1 co-infection: For patients with HCV/HIV-1 co-infection, XR. The potential for drug interactions must be considered before and during follow the dosage recommendations in the table above. (2.2) treatment. Consult the full prescribing information prior to and during • Liver Transplant Recipients: In liver transplant recipients with normal treatment for potential drug interactions. (4, 5.4, 7, 12.3) hepatic function and mild fibrosis (Metavir fibrosis score ≤2), the recommended duration of VIEKIRA XR with ribavirin is 24 weeks. (2.4) See 17 for PATIENT COUNSELING INFORMATION and Medication Guide. DOSAGE FORMS AND STRENGTHS Extended-release tablets: 200 mg dasabuvir, 8.33 mg ombitasvir, 50 mg Revised: 7/2016 paritaprevir, and 33.33 mg ritonavir (3) FULL PRESCRIBING INFORMATION: CONTENTS* 7.1 Potential for VIEKIRA XR to Affect Other Drugs 1 INDICATIONS AND USAGE 7.2 Potential for Other Drugs to Affect One or More Components of 2 DOSAGE AND ADMINISTRATION VIEKIRA XR 2.1 Testing Prior to Initiation of VIEKIRA XR 7.3 Established and Other Potential Drug Interactions 2.2 Recommended Dosage in Adults 7.4 Drugs without Clinically Significant Interactions with VIEKIRA XR 2.3 Use in Liver Transplant Recipients 8 USE IN SPECIFIC POPULATIONS 2.4 Hepatic Impairment 8.1 Pregnancy 3 DOSAGE FORMS AND STRENGTHS 8.2 Lactation 4 CONTRAINDICATIONS 8.3 Females and Males of Reproductive Potential 5 WARNINGS AND PRECAUTIONS 8.4 Pediatric Use 5.1 Risk of Hepatic Decompensation and Hepatic Failure in Patients with 8.5 Geriatric Use Cirrhosis 8.6 Hepatic Impairment 5.2 Increased Risk of ALT Elevations 8.7 Renal Impairment 5.3 Risks Associated With Ribavirin Combination Treatment 10 OVERDOSAGE 5.4 Risk of Adverse Reactions or Reduced Therapeutic Effect Due to Drug 11 DESCRIPTION Interactions 12 CLINICAL PHARMACOLOGY 5.5 Risk of HIV-1 Protease Inhibitor Drug Resistance in HCV/HIV-1 Co­ 12.1 Mechanism of Action infected Patients 12.2 Pharmacodynamics 6 ADVERSE REACTIONS 12.3 Pharmacokinetics 6.1 Clinical Trials Experience 12.4 Microbiology 6.2 Postmarketing Experience 13 NONCLINICAL TOXICOLOGY 7 DRUG INTERACTIONS 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Reference ID: 3962663 14 CLINICAL STUDIES 14.6 Clinical Trial in Subjects with HCV/HIV-1 Co-infection 14.1 Description of Clinical Trials (TURQUOISE-I) 14.2 Clinical Trial Results in Adults with Chronic HCV Genotype 1a and 1b 14.7 Durability of Response Infection without Cirrhosis 16 HOW SUPPLIED/STORAGE AND HANDLING 14.3 Clinical Trial Results in Adults with Chronic HCV Genotype 1a and 1b 17 PATIENT COUNSELING INFORMATION Infection and Compensated Cirrhosis 14.4 Effect of Ribavirin Dose Reductions on SVR12 *Sections or subsections omitted from the full prescribing information are not 14.5 Clinical Trial of Selected Liver Transplant Recipients (CORAL-I) listed. Reference ID: 3962663 FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE VIEKIRA XR is indicated for the treatment of adult patients with chronic hepatitis C virus (HCV) [see Dosage and Administration (2.2) and Clinical Studies (14)]: genotype 1b infection without cirrhosis or with compensated cirrhosis genotype 1a infection without cirrhosis or with compensated cirrhosis for use in combination with ribavirin. 2 DOSAGE AND ADMINISTRATION 2.1 Testing Prior to Initiation of VIEKIRA XR Prior to initiation of VIEKIRA XR, assess for laboratory and clinical evidence of hepatic decompensation [see Warnings and Precautions (5.1 and 5.2)]. 2.2 Recommended Dosage in Adults VIEKIRA XR is a 4-drug fixed-dose combination, extended-release tablet containing 200 mg of dasabuvir, 8.33 mg of ombitasvir, 50 mg of paritaprevir, and 33.33 mg of ritonavir. The recommended dosage of VIEKIRA XR is three tablets taken orally once daily. VIEKIRA XR must be taken with a meal because administration under fasting conditions may result in reduced virologic response and possible development of resistance [see Clinical Pharmacology (12.3)]. Swallow tablets whole. Splitting, crushing, or chewing tablets may compromise the extended-release performance, efficacy, and/or safety of VIEKIRA XR. For optimal release of dasabuvir, alcohol should not be consumed within 4 hours of taking VIEKIRA XR. VIEKIRA XR is used in combination with ribavirin (RBV) in certain patient populations (see Table 1). When administered with VIEKIRA XR, the recommended dosage of RBV is based on weight: 1000 mg/day for subjects <75 kg and 1200 mg/day for those ≥75 kg, divided and administered twice-daily with food. The starting dosage and on-treatment dosage of RBV can be decreased based on changes in hemoglobin levels and/or creatinine clearance. For ribavirin dosage modifications, refer to the ribavirin prescribing information. For patients with HCV/HIV-1 co-infection, follow the dosage recommendations in Table 1. Refer to Drug Interactions (7) for dosage recommendations for concomitant HIV-1 antiviral drugs. Table 1 shows the recommended VIEKIRA XR treatment regimen and duration based on patient population. Reference ID: 3962663 Table 1. Treatment Regimen and Duration by Patient Population (Treatment-Naïve or Interferon-Experienced) Patient Population Treatment* Duration Genotype 1a, VIEKIRA XR + ribavirin 12 weeks without cirrhosis Genotype 1a, with compensated cirrhosis VIEKIRA XR + ribavirin 24 weeks** (Child-Pugh A) Genotype
Load more

Recommended publications
  • Ombitasvir, Paritaprevir/Ritonavir (Technivie )
    Ombitasvir, paritaprevir/ritonavir (Technivie®) National Abbreviated Review Drug Monograph December 2015 VA Pharmacy Benefits Management Services, Medical Advisory Panel, VISN Pharmacist Executives and Office of Public Health The purpose of VA PBM Services drug monographs is to provide a comprehensive drug review for making formulary decisions. Updates will be made when new clinical data warrant additional formulary discussion. Documents will be placed in the Archive section when the information is deemed to be no longer current. FDA Approval Information1 Description/ Technivie is a fixed-dose combination of ombitasvir, paritaprevir, and ritonavir. Mechanism of Action Ritonavir does not have activity against Hepatitis C virus (HCV); it is included in the regimen as a pharmacokinetic enhancer (i.e. increase concentration of paritaprevir). The other two agents are direct-acting antivirals with different mechanisms of action. Ombitasvir is a NS5A inhibitor and paritaprevir is a NS3/4A protease inhibitor. Indication(s) under Review in Fixed-dose combination of ombitasvir, paritaprevir and ritonavir with ribavirin this document is indicated for the treatment of chronic hepatitis C genotype 4 infections in adults without cirrhosis. NOTE: Per prescribing information, this combination may be administered without ribavirin in treatment-naïve patients who cannot tolerate ribavirin Dosage Form(s) Under Ombitasvir, paritaprevir, ritonavir 12.5/75/50mg tablet Review REMS NO REMS Pregnancy Rating Pregnancy Category B; however, when ribavirin is co-administered, then regimen is contraindicated in pregnant women and in men whose female partners are pregnant. Executive Summary1-2 Efficacy The FDA approval of ombitasvir, paritaprevir and ritonavir with ribavirin was primarily based on one phase 2b randomized, open-label, multi-center trial (called PEARL-1).
    [Show full text]
  • Sofosbuvir/Ledipasvir for HIV •
    Hepatitis C: Drugs and Combinations Melissa Osborn MD Associate Professor MetroHealth Medical Center Case Western Reserve University Cleveland, OH Faculty and Planning Committee Disclosures Please consult your program book. Off-Label Disclosure The following off-label/investigational uses will be discussed in this presentation: • Sofosbuvir/ledipasvir for HIV •. Investigational agents for hepatitis C will be mentioned – Asunaprevir – Daclatasvir – Beclabuvir – Grazoprevir – Elbasvir – GS-5816 Learning Objectives Upon completion of this presentation, learners should be better able to: • apply clinical trial data on new hepatitis C therapies to their patient population. • select which new hepatitis C therapies are appropriate to use with common antiretrovirals. Evolution of interferon-based therapy in HCV-monoinfected genotype 1 patients Sustained Virologic Response 100% 90% 80% 80% 75% 67% 60% 42% 46% 40% 28% 20% 7% 0% Std interferon-alfa IFN + RBV Peg-alfa-2b+RBV Peg-alfa-2a +RBV P/R/Telaprevir P/R/Boceprevir P/R/Simeprevir P/R/Sofosbuvir McHutchison, NEJM 1998; 339: 1485-92 Jacobson, NEJM 2011; 364:2405-16 Fried, NEJM 2002; 347: 975-82 Poordad, NEJM 2011; 364: 1195-206 Manns, Lancet 2001; 358:958-65 Jacobson, AASLD 2013 #1122 Lawitz, NEJM 2013 Evolution of HCV Therapy: Genotype 1 Patients Naïve to Therapy: HIV-HCV coinfection Sustained Virologic Response 80% 75% 74% 67% 61% 60% 46% 42% 40% 28% 29% 20% 17% 7% 7% 0% Std interferon-alfa IFN + RBV Peg-alfa-2b+RBV Peg-alfa-2a +RBV P/R/Telaprevir P/R/Boceprevir Torriani, NEJM, 2004 351:438-50
    [Show full text]
  • Hepatitis C Agents Therapeutic Class Review
    Hepatitis C Agents Therapeutic Class Review (TCR) November 2, 2018 No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, digital scanning, or via any information storage or retrieval system without the express written consent of Magellan Rx Management. All requests for permission should be mailed to: Magellan Rx Management Attention: Legal Department 6950 Columbia Gateway Drive Columbia, Maryland 21046 The materials contained herein represent the opinions of the collective authors and editors and should not be construed to be the official representation of any professional organization or group, any state Pharmacy and Therapeutics committee, any state Medicaid Agency, or any other clinical committee. This material is not intended to be relied upon as medical advice for specific medical cases and nothing contained herein should be relied upon by any patient, medical professional or layperson seeking information about a specific course of treatment for a specific medical condition. All readers of this material are responsible for independently obtaining medical advice and guidance from their own physician and/or other medical professional in regard to the best course of treatment for their specific medical condition. This publication, inclusive of all forms contained herein, is intended to be educational in nature and is intended to be used for informational purposes only. Send comments and suggestions to [email protected]. Proprietary Information. Restricted Access – Do not disseminate or copy without approval. © 2004–2018 Magellan Rx Management. All Rights Reserved. FDA-APPROVED INDICATIONS Drug Mfr FDA-Approved Indications Interferons peginterferon alfa-2a Genentech Chronic hepatitis C (CHC) 1 (Pegasys®) .
    [Show full text]
  • 2015 Hepatitis C Second Generation Antivirals (Harvoni [Ledipasvir/Sofosbuvir], and Viekira Pak [Ombitasvir/Paritaprevir/Ritonavir
    2015 Hepatitis C Second Generation Antivirals (Harvoni [ledipasvir/sofosbuvir], and Viekira Pak [ombitasvir/paritaprevir/ritonavir + dasabuvir ]) Prior Authorization – Through Preferred Agents Program Summary 2015 Hepatitis C Second Generation Antivirals (Harvoni [ledipasvir/sofosbuvir], and Viekira Pak [ombitasvir/paritaprevir/ritonavir + dasabuvir]) Prior Authorization – Through Preferred Oral Agent(s) The Hepatitis C First Generation, Hepatitis C Second Generation and Sovaldi Prior Authorization Programs must be implemented together. OBJECTIVE The intent of the Hepatitis C second generation antiviral Prior Authorization (PA) program is to appropriately select patients for therapy according to the Food and Drug Administration (FDA) approved product labeling and/or clinical guidelines and/or clinical studies. The PA process will evaluate the use of these agents when there is supporting clinical evidence of Class IIa, Level C or better for their use. Patients requesting Harvoni that are treatment naïve, non-cirrhotic and with an initial viral load < 6 M IU/mL will be approved for 8 weeks assuming all other criteria are met. This criteria does not include the use of Sovaldi (sofosbuvir), and requests for Sovaldi (sofosbuvir) in combination with Olysio (simeprevir) which will not be approved. For the use of Sovaldi (sofosbuvir) see Sovaldi specific criteria. For the use of Olysio in combination with peginterferon and ribavirin, see Hepatitis C First Generation criteria. For hepatocellular carcinoma patients, see Sovaldi (sofosbuvir) specific criteria. TARGET DRUGS Preferred Agent(s) Harvoni® (ledipasvir/sofosbuvir) Nonpreferred Agent(s) Viekira Pak (ombitasvir/paritaprevir/ritonavir + dasabuvir) PRIOR AUTHORIZATION CRITERIA FOR APPROVAL Harvoni (ledipasvir/sofosbuvir) will be approved when the following criteria are met: 1. The patient has a diagnosis of chronic hepatitis C confirmed by serological markers AND 2.
    [Show full text]
  • Report on the Deliberation Results September 14, 2016 Evaluation and Licensing Division, Pharmaceutical Safety and Environmental
    Report on the Deliberation Results September 14, 2016 Evaluation and Licensing Division, Pharmaceutical Safety and Environmental Health Bureau Ministry of Health, Labour and Welfare Brand Name Rebetol Capsules 200 mg Non-proprietary Name Ribavirin (JAN*) Applicant MSD K.K. Date of Application December 25, 2015 Results of Deliberation In the meeting held on September 9, 2016, the Second Committee on New Drugs concluded that the partial change application for the product may be approved and that this result should be presented to the Pharmaceutical Affairs Department of the Pharmaceutical Affairs and Food Sanitation Council. The re-examination period of the product is the time to the expiration date of the re-examination period for Viekirax Combination Tablets specified at the initial approval (until September 27, 2023). Conditions of Approval The applicant is required to develop and appropriately implement a risk management plan. *Japanese Accepted Name (modified INN) This English translation of this Japanese review report is intended to serve as reference material made available for the convenience of users. In the event of any inconsistency between the Japanese original and this English translation, the Japanese original shall take precedence. PMDA will not be responsible for any consequence resulting from the use of this reference English translation. Review Report August 23, 2016 Pharmaceuticals and Medical Devices Agency The following are the results of the review of the following pharmaceutical products submitted for marketing approvals conducted by the Pharmaceuticals and Medical Devices Agency. Brand Names (a) Viekirax Combination Tablets (b) Rebetol Capsules 200 mg Non-proprietary Names (a) Ombitasvir Hydrate/Paritaprevir Hydrate/Ritonavir (b) Ribavirin Applicants (a) AbbVie GK (b) MSD K.K.
    [Show full text]
  • TECHNIVIE (Ombitasvir, Paritaprevir and Ritonavir) Tablets, for Oral Use WARNINGS and PRECAUTIONS Initial U.S
    HIGHLIGHTS OF PRESCRIBING INFORMATION • Co-administration with drugs that are: highly dependent on CYP3A for These highlights do not include all the information needed to use clearance; moderate and strong inducers of CYP3A. (4) TECHNIVIE safely and effectively. See full prescribing information for • Known hypersensitivity to ritonavir (e.g. toxic epidermal necrolysis, TECHNIVIE. Stevens-Johnson syndrome). (4) TECHNIVIE (ombitasvir, paritaprevir and ritonavir) tablets, for oral use WARNINGS AND PRECAUTIONS Initial U.S. Approval: 2015 • Risk of Hepatitis B Virus Reactivation: Test all patients for evidence of current or prior HBV infection before WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN initiation of HCV treatment. Monitor HCV/HBV coinfected patients for PATIENTS COINFECTED WITH HCV AND HBV HBV reactivation and hepatitis flare during HCV treatment and post- See full prescribing information for complete boxed warning. treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated. (5.1) Hepatitis B virus (HBV) reactivation has been reported, in some cases • Hepatic Decompensation and Hepatic Failure in Patient with Cirrhosis: resulting in fulminant hepatitis, hepatic failure, and death. (5.1) Hepatic decompensation and hepatic failure, including liver transplantation or fatal outcomes, have been reported mostly in patients with cirrhosis. RECENT MAJOR CHANGES Monitor for clinical signs and symptoms of hepatic decompensation, and Boxed Warning 2/2017 discontinue treatment in patients who develop evidence of hepatic Indication and Usage (1) 2/2017 decompensation. (5.2) Dosage and Administration (2.1) 2/2017 • ALT Elevations: Discontinue ethinyl estradiol-containing medications prior to starting TECHNIVIE (alternative contraceptive methods are Dosage and Administration (2.2) 2/2017 recommended).
    [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]
  • Technivie™ (Ombitasvir/Paritaprevir/Ritonavir) and Viekira XR™ (Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir) – Product Discontinuations
    Technivie™ (ombitasvir/paritaprevir/ritonavir) and Viekira XR™ (dasabuvir/ombitasvir/paritaprevir/ritonavir) – Product discontinuations • On May 22, 2018, the FDA announced the discontinuation of AbbVie’s Technivie (ombitasvir/paritaprevir/ritonavir) and Viekira XR (dasabuvir/ombitasvir/paritaprevir/ritonavir). — Both product discontinuations are voluntary and due to changes in treatment practices in the current chronic HCV market in the U.S. and are not related to quality, safety or efficacy issues. • Viekira Pak™ (ombitasvir/paritaprevir/ritonavir with dasabuvir) will continue to be available due to reliance by countries outside the U.S. on FDA approval to support post-approval change to the label. However, Viekira Pak will not be promoted. • Viekira XR and Viekira Pak are indicated for the treatment of adult patients with chronic hepatitis C virus (HCV): — Genotype 1b infection without cirrhosis or with compensated cirrhosis — Genotype 1a infection without cirrhosis or with compensated cirrhosis for use in combination with ribavirin. — Viekira XR is a 4-drug fixed-dose combination, extended-release tablet containing dasabuvir 200 mg, ombitasvir 8.33 mg, paritaprevir 50 mg and ritonavir 33.33 mg that is dosed once daily. — Viekira Pak is a 3-drug fixed dose combination tablet containing ombitasvir 12.5 mg, paritaprevir 75 mg and ritonavir 50 mg copackaged with dasabuvir 250 mg tablets. The combination tablet is taken once daily and the dasabuvir tablet is taken twice daily. • Technivie is indicated in combination with ribavirin for the treatment of patients with genotype 4 chronic HCV infection without cirrhosis or with compensated cirrhosis. • Until January 1, 2019, supply of Technivie and Viekira XR will be available for all patients who begin therapy prior to July 1, 2018 to ensure that they are able to complete their course of prescribed therapy.
    [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]
  • Efficacy of NS5A Inhibitors Against Hepatitis C Virus Genotypes 1-7
    Gastroenterology 2018;154:1435–1448 Efficacy of NS5A Inhibitors Against Hepatitis C Virus Genotypes 1–7 and Escape Variants Judith M. Gottwein, Long V. Pham, Lotte S. Mikkelsen, Lubna Ghanem, Santseharay Ramirez, Troels K. H. Scheel, Thomas H. R. Carlsen, and Jens Bukh Copenhagen Hepatitis C Program, Department of Infectious Diseases and Clinical Research Centre, Hvidovre Hospital and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark Hepatitis C virus NS5A inhibitors pibrentasvir and velpatasvir show pangenotypic efficacy HCV genotype Size~EC50 1 5 2 6 3 7 4 Pibrentasvir showed highest efficacy against hepatitis C virus genotype 1-7 escape variants Daclatasvir Ledipasvir Induction of escape Sequencing of genotype 1-7 Reverse genetics Fold Ombitasvir NS5A domain I Resistance testing Resistance (log10) Elbasvir Ruzasvir 6 Velpatasvir 4 2 Pre-existing Y93H results in escape variants with increased fitness and resistance Pibrentasvir 28 30 31 Δ32 93 Pre-existing Y93H Original .5 .0 .5 .0 .5 0 1 2 3 4 5 6 -1 -1 -0 0 0 Fitness + Fold Resistance (log10) (titer difference, log10) BACKGROUND & AIMS: Inhibitors of the hepatitis C virus For the remaining NS5A inhibitors tested, RAS at amino (HCV) NS5A protein are a key component of effective treatment acids 28 and 93 led to high levels of resistance. Among regimens, but the genetic heterogeneity of HCV has limited the these inhibitors, velpatasvir was more effective against variants efficacy of these agents and mutations lead to resistance. We with RAS at amino acid 30 and some variants with RAS at BASIC AND fi directly compared the ef cacy of all clinically relevant NS5A amino acid 31 than the other agents.
    [Show full text]
  • Ombitasvir+Paritaprevir+Ritonavir + Dasabuvir Agents
    Market Applicability Market GA MD NJ NY Applicable NA NA X X Ombitasvir+paritaprevir+ritonavir + dasabuvir Agents Override(s) Approval Duration Prior Authorization Based on Genotype, Treatment status, Quantity Limit or Cirrhosis status Medication Quantity Limit Viekira Pak 4 tablets per day (ombitasvir + paritaprevir + ritonavir + dasabuvir) APPROVAL DURATION Genotype and Status (HCV mono- Associated Treatment Total Approval Duration infected or HCV/HIV-1 co- Regimens of ombitasvir + infecteda) paritaprevir + ritonavir + dasabuvir agents (Viekira Pak) Genotype 1b (treatment naïve or Viekira Pak 12 weeks dual P/R2b treatment-experienced, with compensated cirrhosis or without cirrhosis) Genotype 1a, unknown Genotype 1 Viekira Pak+ RBV 12 weeks subtype, or mixed Genotype 1 subtypes (treatment naïve or dual P/R2b treatment-experienced, without cirrhosis) Genotype 1a, unknown Genotype 1 Viekira Pak+ RBV 24 weeksb subtype, or mixed Genotype 1 subtypes (treatment-naïve or dual P/R2b treatment-experienced, with compensated cirrhosis) APPROVAL CRITERIA Requests for ombitasvir + paritaprevir + ritonavir + dasabuvir (Viekira Pak) may be approved if the following criteria are met: I. Individual is 18 years of age or older; AND PAGE 1 of 6 04/01/2021 This policy does not apply to health plans or member categories that do not have pharmacy benefits, nor does it apply to Medicare. Note that market specific restrictions or transition-of-care benefit limitations may apply. CRX-ALL-0703-21 Market Applicability Market GA MD NJ NY Applicable NA NA X X II. Documentation is provided for a diagnosis of chronic hepatitis C (CHC) infectiona, which includes genotype and a positive HCV RNA result (AASLD/IDSA 2017, CDC 2013); AND III.
    [Show full text]
  • Hepatitis C Antivirals and Combinations, Direct Acting
    Therapeutic Class Overview Direct Acting Hepatitis C Antivirals and Combinations Overview/Summary: The direct acting hepatitis C antiviral and combination products are all Food and Drug Administration (FDA)-approved for the treatment of chronic hepatitis C virus (HCV) infection; although, differences in indications exist relating to use in specific genotypes, with certain combination therapies and other patient factors.1-5 HCV is an enveloped ribonucleic acid virus that is transmitted through exposure with infected blood and is the most common bloodborne infection in the United States, with an estimated prevalence of 3.2 million people chronically infected. Chronic HCV develops in 70 to 85% of HCV-infected persons and is associated with significant morbidity (e.g., cirrhosis, hepatocellular carcinoma [HCC]) and is the leading cause of liver transplantation.7,8 The average annual incidence rate of HCC in the U.S. between 2001 and 2006 was 3.0 per 100,000 people, with 48% to cases attributed to HCV.9 These agents act via several different mechanisms of action and include inhibition of non-structural (NS) 3/4A protease, NS5B polymerase and HCV NS5A.1-6 The hepatitis C protease inhibitors boceprevir (Victrelis®) and simeprevir (Olysio®) both work via inhibition of the HCV NS3/4A protease of HCV genotype 1a and 1b thus preventing replication of HCV host cells.1-2 Similarly, sofosbuvir (Sovaldi®) inhibits HCV NS5B polymerase which also prevents the replication of HCV host cells, however, it is active against multiple genotypes of HCV.3 The two combination products that include direct acting hepatitis C antivirals include ledipasvir/sofosbuvir (Harvoni®) and a 4-drug regimen of ombitasvir/paritaprevir/ritonavir & dasabuvir (Viekira Pak®).
    [Show full text]