title: Long-term safety and tolerability of entecavir in patients with chronic hepatitis B in the rollover study ETV-901.
abstract: OBJECTIVE
  To review long-term safety data from the rollover study ETV-901, focusing on adverse events (AEs) with a potential nucleos(t)ide association.
  
  
  METHODS
  The open-label study ETV-901 (AI463901) assessed the safety of entecavir in chronic hepatitis B patients who received entecavir, lamivudine or adefovir monotherapy in previous entecavir Phase II/III studies. Long-term cumulative safety results are based on reported AEs, regardless of causal relationship.
  
  
  RESULTS
  Median exposure to entecavir in study ETV-901 was 184 weeks. Commonly reported AEs (≥ 10%) were upper respiratory tract infection, headache and nasopharyngitis. Most AEs were mild to moderate; 203 (19%) patients reported grade 3 - 4 AEs, with 45 (4%) considered related to entecavir. There were 14 (1%) discontinuations due to AEs. On-treatment alanine aminotransferase (ALT) flares were reported in 32 (3%) patients and were associated with a reduction in hepatitis B virus DNA of more than 2 log(10) copies/ml in 25/32 patients. AEs potentially associated with nucleos(t)ide analogs were infrequent, the most common being myalgia (n = 54; 5%) and neuropathy-related AEs (hypoparesthesia and hyperparesthesia, polyneuropathy; n = 42; 4%).
  
  
  CONCLUSIONS
  Long-term administration of entecavir was associated with low rates of serious AEs, discontinuations due to AEs and ALT flares. AEs potentially associated with nucleos(t)ide use occurred at low rates.
authors.affiliation: Medical School of Hannover, Department of Gastroenterology, Hepatology and Endocrinology, Carl-Neuberg Str. 1, 30625 Hannover, Germany. manns.michael@mh-hannover.de
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.forename: Ulus S
authors.initials: US
authors.lastname: Akarca
authors.forename: Ting-Tsung
authors.initials: TT
authors.lastname: Chang
authors.forename: William
authors.initials: W
authors.lastname: Sievert
authors.forename: Seung Kew
authors.initials: SK
authors.lastname: Yoon
authors.forename: Naoky
authors.initials: N
authors.lastname: Tsai
authors.forename: Albert
authors.initials: A
authors.lastname: Min
authors.forename: Andreas
authors.initials: A
authors.lastname: Pangerl
authors.forename: Suzanne
authors.initials: S
authors.lastname: Beebe
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
authors.forename: Suchat
authors.initials: S
authors.lastname: Wongcharatrawee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; C413685:entecavir; D006147:Guanine