Pibrentasvir

Total Page:16

File Type:pdf, Size:1020Kb

Pibrentasvir Pibrentasvir Lars Maul, Felix Möser, Mariana Müller Nieva and Lea Neumann July 01, 2020 Contents 1 Introduction 1 2 Basic Information 1 3 Structural analysis 2 3.1 Classification ....................................................... 2 3.2 Structural differences between Ombitasvir and Pibrentasvir ........................... 2 4 Application as a pharmaceutical 3 4.1 Underlying disease .................................................... 3 4.2 Combination of the drug and therapy ........................................ 4 4.3 Effect of Maviret ..................................................... 4 4.4 Properties of Maviret .................................................. 4 4.5 Side effects and interdependencies with other drugs ............................... 5 4.6 Alternatives ........................................................ 5 1 Introduction The active ingredient Pibrentasvir is used for the treatment of the six genotypes of the Hepatitis-C virus. The antiviral drug belongs to the class of NS5A inhibitors. It is used as a fixed combination with Glecaprevir in the drug Maviret. In the following article, the NS5A inhibitor will be introduced in more detail. First, basic information will be presented leading over to the structural analysis of the molecule. At this point, the focus will be set on the structural comparison to a first-generation NS5A inhibitor and the significance of these changes. Finally, the use of the molecule Pibrentasvir as the drug Maviret will be explained. 2 Basic Information IUPAC: methylN-[(2S,3R)-1-[(2S)-2-[6-[(2R,5R)-1-[3,5-difluoro-4-[4-(4-fluorophenyl)piperidin-1-yl]phenyl]-5-[6-fluoro- 2-[(2S)-1-[(2S,3R)-3-methoxy-2-(methoxycarbonylamino)butanoyl]pyrrolidin-2-yl]-3H-benzimidazol-5-yl]pyrrolidin- 2-yl]-5-fluoro-1H-benzimidazol-2-yl]pyrrolidin-1-yl]-3-methoxy-1-oxobutan-2-yl]carbamate At standard states of temperature and pressure Pibrentasvir (C57H65F5N10O8, M = 1113.2 g/mol) exists as a white or slightly yellow crystalline powder. It’s an HCV NS5A-Inhibitor which is used for the treatment of the Hepatitis-C virus. The medicine is produced as a fixed combination of the active agents Pibrentasvir and Glecaprevir. The drug is called Maviret and is produced by AbbVie. This fixed combination of the active agents was licensed in 2017 for usage in the EU, Switzerland and theUSA.In the human body, Pibrentasvir is not metabolized and almost exclusively bound to human plasma proteins. When it is 1 absorbed by healthy subjects the mean peak plasma concentration is reached after 5 hours. In non-cirrhotic Hepatitis-C infected subjects the mean peak plasma concentration is about 110 ng/ml. The excretion of the agent is biliary-faecal with an elimination half-life about 13 hours. The agent is not excreted in the urine meaning that the treatment of a patient with renal failure is possible. In combination with Glecaprevir, the bioavailability can be improved compared to a sole administration of Pibrentasvir. Pibrentasvir is not genotoxic according to in vitro or in vivo studies. In rodent studies, it has also been shown that it has no effect on mating, female or male fertility, or early embryonic development. 3 Structural analysis 3.1 Classification This compound belongs to the class of organic compounds known as phenylpiperidines. These are compounds contain- ing a phenylpiperidine skeleton which consists of piperidine bound to a phenyl group. Kingdom: Organic compounds Super class: Organoheterocyclic compounds Class: Piperidines Sub Class: Phenylpiperidines 3.2 Structural differences between Ombitasvir and Pibrentasvir First-generation NS5A inhibitors do not show equivalent efficacy against all genotypes of the HCV virus 1-6 andare prone to drug resistance. Modification of the anchor, symmetric linker and end-cap architecture (figure 2) andalter- ation of the pyrrolidine stereochemistry of Ombitasvir (figure 1), which is a first-generation NS5A inhibitor, results in significant improvements of genotype coverage and resistance-profile while maintaining the strong antiviral properties of Ombitasvir. First, the linker regions are changed from a phenyl amide linker to a benzimidazole linker and the stereochemical bonds at the pyrrolidine core are changed from 2S,5S to 2R,5R. These changes show strong activity against all tested genotypes and by changing the stereochemistry especially the inhibition of HCV replication of genotypes 1-4 could be improved. On this basis, further structural changes are made to improve the pharmacokinetic profile. The intent is to improve the potencies with comparable activities towards the different HCV genotypes as well as to maintain activity against amino acid substitutions usually selected as resistant variants by first-generation NS5A inhibitors. An exchange of the tert-butyl group with 4-fluorophenyl-substituted piperidine leads to a potency-increasing effect, especially with the doubly fluorinated benzene. An improved oral exposure can be achieved due to the larger and lipophilic anchor. An improvement in plasma exposure is also achieved by fluorinating the benzimidazole linkers. Finally, the moc-Val end-caps are varied to moc-Thr(OMe) groups. This variation shows the best EC50 potencies across all genotypes and the least protein binding attenuation effects. Pibrentasvir also shows a significantly improved resistance profile. These changes lead to the development of the molecule Pibrentasvir (figure 3) with the properties of a next-generation NS5A inhibitor. Thus Pibrentasvir shows strong activity in genotypes 1-6. The tendency to develop drug resistance in all common genotypes was also greatly reduced. A sufficient plasma exposure upon oral administration to suppress HCV replication exists and Pibrentasvir has the ability to be combined with another mechanistically orthogonal antiviral agent. 2 Figure 1: structure Ombitasvir Figure 2: schematic structure Figure 3: structure Pibrentasvir 4 Application as a pharmaceutical 4.1 Underlying disease Pibrentasvir is used in pharmaceuticals in combination with Glecaprevir. Glecaprevir / Pibrentasvir (G/P), sold under the brand names Mavyret and Maviret, is a medication used to treat Hepatitis C. It works against all six types of hepatitis C, labelled 1 through 6. There are also subtypes labelled with letters for example genotypes 1a and 1b. Most people are infected by a single, dominant genotype, but it is possible to have more than one at the same time. Hepatitis-C is usually chronic and can lead to severe liver diseases such as cirrhosis and liver cancer. The pathogen is the Hepatitis- C-virus (HCV), which is a single-stranded RNA-virus. The NS5A protein, which stands for non-structural protein 5A, is an important part of the development of the Hepatitis-C-virus. The zinc-binding protein is a large hydrophilic phos- phoprotein that is involved in the RNA-replication. It is also essential for the later stages of the viral life cycle of HCV which includes the assembly of viral particles which leads to infectious virions as well as complex interdependencies 3 with cellular functions. The last point includes the inhibition of apoptosis and the promotion of tumorigenic processes. Both play an important role in the initiation of carcinogenic processes. The proline-rich protein consists of 447 amino acids and is characterized by three domains. Domain I is a zinc-binding domain and Domain II and III are unstructured. All three domains are able to bind the RNA. 4.2 Combination of the drug and therapy Maviret is a combination of Pibrentasvir and Glecaprevir. One pill contains 100 mg Glecaprevir and 40 mg Pibrentasvir. In addition to these main active agents, the drug contains several other active substances like lactose-monohydrates. The usual processing time is about 8 to 12 weeks and is influenced by possible liver issues. The active substances are decomposed by the liver. One treatment costs about 30000 euros. 4.3 Effect of Maviret The drug prevents virus replication as well as the production of new virus components in the cell. Maviret shows a direct antiviral or virostatic effect. Pibrentasvir acts as an NS5A inhibitor which can reduce the HCV RNA blood level. Forthis purpose, Pibrentasvir binds to the NS5A protein which is responsible for the virus’ RNA replication (figure 4). The active substance prevents the virus from reprogramming the cells. It binds directly to the NS5A protein outside and within the cell and thus prevents the direct docking to the individual cell organelles. Furthermore, the transport of the viruses into the cell is prevented by inhibiting a special transport protein, the p-glycoprotein. In addition, glecaprevir acts as an inhibitor of the HCV NS3 / 4A protease, which is also responsible for RNA replication and thus virus replication. The combination of several direct-acting agents with different molecular targets enables sustained virus suppression while avoiding antiviral resistance. In addition to a direct antiviral agent, Maviret also represents a blockade that prevents the viruses from reaching the corresponding host cells in the first place. Figure 4: NS5A inhibitor’s mechanism of action [18] 4.4 Properties of Maviret Maviret works on all six genotypes of the Hepatitis-C virus and shows a direct antiviral effect. It can be used for patients who suffer from mild to moderate liver cirrhosis and HIV co-infection. Patients with kidney diseases can betreated as well due to the excretion of the active ingredient being biliary-faecal. Furthermore, studies have shown that 99% of patients without cirrhosis
Recommended publications
  • Avis De La Commission De La Transparence
    COMMISSION DE LA TRANSPARENCE Avis 6 décembre 2017 Date d’examen par la Commission : 22 novembre 2017 glécaprévir / pibrentasvir MAVIRET 100 mg/40 mg, comprimé pelliculé B/ 84 (CIP 34009 301 087 6 5) Laboratoire ABBVIE Code ATC Code ATC non encore attribué (association d’antiviraux à action directe) Motif de l’examen Inscription Sécurité Sociale (CSS L.162-17) Listes concernées Collectivités (CSP L.5123-2) Indications « Traitement de l’infection chronique par le virus de l’hépatite C (VHC) de concernées génotypes 1 à 6 chez les adultes » HAS - Direction de l'Evaluation Médicale, Economique et de Santé Publique 1/28 Avis 2 SMR Important Compte tenu de : - son efficacité virologique pangénotypique importante (>90%), avec une durée de traitement de 8 à 12 semaines pour la majorité des patients sans cirrhose ou avec cirrhose compensée (Child-Pugh A uniquement), - la démonstration d’une efficacité importante dans des populations particulières telles que les patients insuffisants rénaux ou hémodialysés pour lesquelles les alternatives sont limitées, - son profil de tolérance et de résistance satisfaisant mais avec un ASMR potentiel d’interactions médicamenteuses important, - l’existence d’alternatives qui permettent également un traitement court (8 à 12 semaines) sans adjonction de ribavirine, la Commission considère que la spécialité, apporte, au même titre que les autres combinaisons d’antiviraux d’action directe disponibles (EPCLUSA, HARVONI, VIEKIRAX, EXVIERA, ZEPATIER), une amélioration du service médicale rendue mineure (ASMR IV) dans
    [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]
  • Hepatitis C Treatment
    Hepatitis C Treatment The goal of treatment for hepatitis C virus (HCV) is to cure the virus, which can be done with a combination of drugs. The specific meds used and the duration of treatment depend on a number of factors, including HCV genotype (genetic structure of the virus), viral load, past treatment experience, degree of liver damage, ability to tolerate the prescribed treatment, and whether the person is waiting for a liver transplant or is a transplant recipient. In some cases, HCV treatment may be limited by your health insurance plan or drug formulary. Here’s information about each type, or class, of approved HCV treatment along with drugs in the late stages of development: Multi-Class Combination Drugs Brand Name Generic Name Status Pharmaceutical Company Epclusa* sofosbuvir + velpatasvir Approved Gilead Sciences Harvoni* ledipasvir + sofosbuvir Approved Gilead Sciences Mavyret glecaprevir + pibrentasvir Approved AbbVie Vosevi sofosbuvir/velpatasvir/ Approved Gilead Sciences voxilaprevir Zepatier elbasvir + grazoprevir Approved Merck n/a daclatasvir + asunaprevir + Phase III Bristol-Myers Squibb beclabuvir *generic available What are they? Multi-class combination drugs are a combination of drugs formulated into a single pill or package of pills. For instance, the drug Harvoni combines two drugs, ledipasvir and sofosbuvir. Ledipasvir is an NS5A inhibitor and is only sold as part of Harvoni; sofosbuvir may be prescribed separately under the brand name of Sovaldi. Pegylated Interferon Alfa Brand Name Generic Name Status Pharmaceutical Company Pegasys peginterferon alfa-2a Approved Genentech What are they? Interferon is a protein made by the immune system, named because it interferes with viral reproduction. In addition, interferon signals the immune system to recognize and respond to microorganisms, including viral and bacterial infections.
    [Show full text]
  • Real-Life Effectiveness and Safety of Glecaprevir/Pibrentasvir for Korean Patients with Chronic Hepatitis C at a Single Institution
    Gut and Liver https://doi.org/10.5009/gnl19393 pISSN 1976-2283 eISSN 2005-1212 Original Article Real-Life Effectiveness and Safety of Glecaprevir/Pibrentasvir for Korean Patients with Chronic Hepatitis C at a Single Institution Young Joo Park1,2, Hyun Young Woo1,2, Jeong Heo1,2, Sang Gyu Park3, Young Mi Hong1,4, Ki Tae Yoon1,4, Dong Uk Kim1,2, Gwang Ha Kim1,2, Hyung Hoi Kim2,5, Geun Am Song1,2, and Mong Cho1,4 1Department of Internal Medicine, College of Medicine, Pusan National University, 2Biomedical Research Institute, Pusan National University Hospital, 3Department of Internal Medicine, Good Samsun Hospital, Busan, 4Liver Center, Pusan National University Yangsan Hospital, Yangsan, and 5Department of Laboratory Medicine, College of Medicine, Pusan National University, Busan, Korea Article Info Background/Aims: Glecaprevir/pibrentasvir (G/P) is a combination of direct-acting antiviral Received November 21, 2019 agents that is an approved treatment for chronic infections by all six hepatitis C virus (HCV) geno- Revised June 3, 2020 types. However, there are limited data on the effect of G/P in Korean patients in actual real-world Accepted June 21, 2020 settings. We evaluated the real-life effectiveness and safety of G/P at a single institution in Korea. Published online August 26, 2020 Methods: This retrospective, observational, cohort study used sustained virologic response at 12 weeks after treatment completion (SVR12) as the primary effectiveness endpoint. Safety and Corresponding Author tolerability were also determined. Jeong Heo Results: We examined 267 individuals who received G/P for chronic HCV infections. There were ORCID https://orcid.org/0000-0003-0961-7851 148 females (55.4%), and the overall median age was 63.0 years (range, 25 to 87 years).
    [Show full text]
  • Effectiveness and Safety of Sofosbuvir/Velpatasvir ± Ribavirin Vs
    Original research Eur J Hosp Pharm: first published as 10.1136/ejhpharm-2019-002060 on 7 February 2020. Downloaded from Effectiveness and safety of sofosbuvir/velpatasvir ± ribavirin vs glecaprevir/pibrentasvir in genotype 3 hepatitis C virus infected patients Luis Margusino- Framiñán,1,2 Purificación Cid- Silva,1,2 Sandra Rotea- Salvo,1 Álvaro Mena- de- Cea,2,3 Francisco Suárez- López,4 Pilar Vázquez- Rodríguez,2,3 Manuel Delgado- Blanco,2,4 Ana Isabel Sanclaudio- Luhia,5 Isabel Martín- Herranz,1 Ángeles Castro- Iglesias2,3 1Pharmacy Service, Universitary ABSTRact 1.1%, with a total affected population of 5.6 million Hospital of A Coruña, A Objectives Sofosbuvir/velpatasvir±ribavirin (SOF/ people.1 The prevalence of HCV genotypes varies Coruña, Spain 2 among regions, with genotype 3 (G3) being the Division of Clinical Virology, VEL±RBV) and glecaprevir/pibrentasvir (GLE/PIB) are Biomedical Research Institute the drug combinations of choice for treating individuals second most prevalent in Europe after genotype 1 of A Coruña (INIBIC), with genotype 3 hepatitis C virus (G3- HCV) infection. The (G1), accounting for approximately 25% of cases Universitary Hospital of A objective of this study was to evaluate the effectiveness of chronic hepatitis C (CHC).2 Compared with Coruña (CHUAC), Sergas, and safety of SOF/VEL±RBV compared with GLE/PIB for G1- HCV, G3- HCV chronic infection has a faster University of A Coruña (UDC), 3–6 A Coruña, Spain treating G3- HCV infection under routine clinical practice progression to liver cirrhosis and hepatocellular
    [Show full text]
  • MAVYRET Safely and Effectively
    HIGHLIGHTS OF PRESCRIBING INFORMATION • Recommended dosage in adults: Three tablets taken at the same time orally These highlights do not include all the information needed to use once daily (total daily dose: glecaprevir 300 mg and pibrentasvir 120 mg) MAVYRET safely and effectively. See full prescribing information for with food. (2.3) MAVYRET. • Recommended dosage in pediatric patients 3 years and older: Pediatric Patients 3 Years to Less than 12 Years Old: Dosing is based MAVYRET® (glecaprevir and pibrentasvir) tablets, for oral use on weight. Refer to Table 3 of the full prescribing information for MAVYRET® (glecaprevir and pibrentasvir) oral pellets specific dosing guidelines based on body weight. (2.4) Instructions for Initial U.S. Approval: 2017 Use should be followed for preparation and administration of MAVYRET oral pellets. (2.5) WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION Pediatric Patients 12 Years of Age and Older, or Pediatric Patients IN PATIENTS COINFECTED WITH HCV AND HBV Weighing at Least 45 kg: three tablets taken at the same time orally See full prescribing information for complete boxed warning. once daily (total daily dose: glecaprevir 300 mg and pibrentasvir 120 mg) with food. (2.4) Hepatitis B virus (HBV) reactivation has been reported, in some • HCV/HIV-1 co-infection and patients with any degree of renal impairment: cases resulting in fulminant hepatitis, hepatic failure, and death. Follow the dosage recommendations in the tables above. (2.2) (5.1) • Liver or Kidney Transplant Recipients: MAVYRET is recommended for 12 weeks in patients 3 years and older who are liver or kidney transplant recipients.
    [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]
  • 5.01.606 Hepatitis C Antiviral Therapy
    PHARMACY POLICY – 5.01.606 Hepatitis C Antiviral Therapy Effective Date: Aug. 1, 2021 RELATED MEDICAL POLICIES: Last Revised: July 9, 2021 None Replaces: 5.01.11 Select a hyperlink below to be directed to that section. POLICY CRITERIA | DOCUMENTATION REQUIREMENTS | CODING RELATED INFORMATION | EVIDENCE REVIEW | REFERENCES | HISTORY ∞ Clicking this icon returns you to the hyperlinks menu above. Introduction Hepatitis C is caused by a virus that infects the liver. Sometimes the virus clears up on its own within a few months. This is called acute hepatitis C. In other cases, the infection lasts a long time. This is known as chronic hepatitis C. A person might be unaware of chronic hepatitis C because in the early stages the infection usually shows no symptoms or very mild symptoms. The drugs used to treat hepatitis C vary, but most of the newer antiviral drugs require a genetic test. This is because hepatitis C has different genetic types and certain drugs target specific genetic types. Other factors determining which drug may be recommended is whether other drugs were tried first and the status of a person’s current medical condition. This policy describes the criteria when hepatitis C drugs may be considered medically necessary. Note: The Introduction section is for your general knowledge and is not to be taken as policy coverage criteria. The rest of the policy uses specific words and concepts familiar to medical professionals. It is intended for providers. A provider can be a person, such as a doctor, nurse, psychologist, or dentist. A provider also can be a place where medical care is given, like a hospital, clinic, or lab.
    [Show full text]
  • HCV Medications
    HCV Medications OVERVIEW Hepatitis C virus (HCV) infection causes liver inflammation that can lead to liver problems, including cancer. People who have chronic HCV need medication to treat it. HCV drugs can help clear the virus from the body and ease symptoms. Even if an HCV infection hasn’t caused symptoms yet, it’s still important to treat it. This is because drugs can also lower the risk of complications from HCV, such as dangerous liver problems. HCV has different genetic variationsgenotypes ( ). The medication prescribed for HCV depends on the genotype a person has. Genotype 1 is the most common type in the U.S. Here are the medications available to treat HCV, plus some helpful information about what to expect with their treatment. Read more about U.S HCV therapy guidelines, including simplified treatment regimens that cover all genotypes. DIRECT ACTING ANTIVIRALS (DAAs) Direct-acting antivirals (DAAs) are currently the standard of care for chronic HCV infection. These drugs work by attacking HCV directly, which means they’re more targeted than older treatments such as interferons (see below). Additionally, they don’t affect as many systems in the body as interferons, so they may not cause as many side effects. All DAAs are oral drugs. Side effects of DAAs can include: anemia diarrhea fatigue headaches nausea vomiting slow heartbeat grazoprevir Grazoprevir is an HCV protease inhibitor. Protease inhibitors work by stopping viruses from multiplying. Grazoprevir has good activity against a range of HCV genotypes, including some that are resistant to most currently used DAAs. It’s only available in combination with elbasvir and sold as grazoprevir/elbasvir (Zepatier) [see below].
    [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]
  • Resistance Analysis of a 3-Day Monotherapy Study with Glecaprevir Or Pibrentasvir in Patients with Chronic Hepatitis C Virus Genotype 1 Infection
    viruses Article Resistance Analysis of a 3-Day Monotherapy Study with Glecaprevir or Pibrentasvir in Patients with Chronic Hepatitis C Virus Genotype 1 Infection Teresa I. Ng 1,*, Tami Pilot-Matias 1, Rakesh Tripathi 1, Gretja Schnell 1, Preethi Krishnan 1, Thomas Reisch 1, Jill Beyer 1, Tatyana Dekhtyar 1, Michelle Irvin 1, Liangjun Lu 1, Armen Asatryan 1, Andrew Campbell 1, Betty Yao 1, Sandra Lovell 1, Federico Mensa 1, Eric J. Lawitz 2, Jens Kort 1 ID and Christine Collins 1 1 AbbVie, Inc., North Chicago, IL 60064, USA; [email protected] (T.P.-M.); [email protected] (R.T.); [email protected] (G.S.); [email protected] (P.K.); [email protected] (T.R.); [email protected] (J.B.); [email protected] (T.D.); [email protected] (M.I.); [email protected] (L.L.); [email protected] (A.A.); [email protected] (A.C.); [email protected] (B.Y.); [email protected] (S.L.); [email protected] (F.M.); [email protected] (J.K.); [email protected] (C.C.) 2 Texas Liver Institute, University of Texas Health San Antonio, San Antonio, TX 78215, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-(847)-937-1375 Received: 18 July 2018; Accepted: 27 August 2018; Published: 28 August 2018 Abstract: Glecaprevir (an NS3/4A protease inhibitor) and pibrentasvir (an NS5A inhibitor) are potent and pangenotypic hepatitis C virus (HCV) direct-acting antivirals. This report describes the baseline polymorphisms and treatment-emergent substitutions in NS3 or NS5A detected in samples from HCV genotype 1-infected patients receiving 3-day monotherapy of glecaprevir or pibrentasvir, respectively.
    [Show full text]