title: Ledipasvir-sofosbuvir: interferon-/ribavirin-free regimen for chronic hepatitis C virus infection.
abstract: OBJECTIVE
  To review the pharmacology, efficacy, and safety of ledipasvir-sofosbuvir for the treatment of chronic hepatitis C virus (HCV).
  
  
  METHODS
  A literature search through clinicaltrials.gov, EMBASE, and PubMed was conducted (January 1966 to October 2014) using the terms ledipasvir, sofosbuvir, GS-5885, and GS-7977. References from retrieved articles and abstracts presented at recent meetings were reviewed for any additional material. The prescribing information was also reviewed.
  
  
  METHODS
  Phase 1, 2, and 3 human and animal studies describing the pharmacology, pharmacokinetics, efficacy, and safety of ledipasvir and sofosbuvir for HCV were identified.
  
  
  RESULTS
  Ledipasvir-sofosbuvir, a fixed-dose combination (FDC) tablet inhibiting nonstructural (NS) 5A and 5B proteins, without peginterferon and ribavirin is indicated for adult patients with genotype 1 HCV infection who are treatment naïve or experienced, with or without cirrhosis. Pivotal trials (n = 1952) have demonstrated that once-daily administration of ledipasvir-sofosbuvir for 12 or 24 weeks is effective at achieving sustained virological response (SVR) rates (94%-99%) in treatment-naïve patients (12 weeks), treatment-experienced patients without cirrhosis (12 weeks), and treatment-experienced patients with cirrhosis (24 weeks). Treatment-naïve patients without cirrhosis and baseline viral levels of less than 6 million IU/mL may be considered for 8 weeks of treatment. The most common adverse drug events (ADEs) associated with ledipasvir-sofosbuvir include headache, fatigue, insomnia, nausea, and diarrhea.
  
  
  CONCLUSIONS
  Ledipasvir-sofosbuvir is the first interferon- and ribavirin-free FDC agent that has SVR rates much greater than 94%, with minimal ADEs, for the treatment of chronic HCV genotype 1 in naïve and treatment-experienced patients.
authors.affiliation: University of the Sciences, Philadelphia, PA, USA mic.smith@usciences.edu.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Smith
authors.affiliation: University of Illinois at Chicago, IL, USA University of Illinois Hospital and Health Sciences Center, Chicago, IL, USA.
authors.forename: Juliana
authors.initials: J
authors.lastname: Chan
authors.affiliation: University of Michigan College of Pharmacy, Ann Arbor, MI, USA University of Michigan Health Systems, Ann Arbor, MI, USA.
authors.forename: Rima A
authors.initials: RA
authors.lastname: Mohammad
mesh_terms: D000328:Adult; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004359:Drug Therapy, Combination; D005449:Fluorenes / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D005838:Genotype; D006261:Headache / Q000139:chemically induced / Q000453:epidemiology; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007372:Interferons / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000453:epidemiology; D009325:Nausea / Q000139:chemically induced / Q000453:epidemiology; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000069474:Sofosbuvir; D014542:Uridine Monophosphate / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; C586541:ledipasvir; D012254:Ribavirin; D007372:Interferons; D014542:Uridine Monophosphate; D000069474:Sofosbuvir
keywords: hepatitis C virus; ledipasvir; sofosbuvir