title: A pilot evaluation of the safety and tolerability of repeat dose administration of long-acting injectable naltrexone (Vivitrex) in patients with alcohol dependence.
abstract: BACKGROUND
  : Oral naltrexone is currently used as part of a treatment regimen for alcohol-dependent patients, but its clinical utility is hampered by poor patient adherence. A long-acting injectable naltrexone formulation (Vivitrex) was designed to facilitate patient adherence by providing an extended duration of therapeutic naltrexone over 1 month, thereby eliminating the need for daily dosing.
  
  
  METHODS
  : A multicenter, randomized, double-blind, placebo-controlled pilot study was conducted to evaluate the safety and tolerability of intramuscular repeat dose administration of this extended-release naltrexone formulation in DSM-IV alcohol-dependent patients. Thirty patients were randomized to treatment with injectable naltrexone (400 mg; n = 25) or a matching placebo injection (n = 5) and were dosed once every 28 days over 4 months. Psychosocial treatment was offered to patients in both treatment groups. Outcome measures related to drinking activity and trough plasma concentrations of naltrexone and its primary metabolite, 6-beta-naltrexol, were evaluated.
  
  
  RESULTS
  : Injectable naltrexone was generally safe and well tolerated. Reported adverse events were mild to moderate and resolved without intervention; only two patients discontinued due to adverse events. The most common adverse events (nausea and headache) occurred at a similar rate for patients in both treatment groups. Pharmacokinetic analysis confirmed that therapeutic levels of naltrexone were delivered throughout the four 1-month treatment cycles.
  
  
  CONCLUSIONS
  : The results of this pilot study provide the basis and methods for a larger, more definitive trial to determine the utility of this long-acting injectable naltrexone formulation in the treatment of alcohol-dependent patients.
authors.affiliation: University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, USA. bjohnson@uthscsa.edu
authors.forename: Bankole A
authors.initials: BA
authors.lastname: Johnson
authors.forename: Nassima
authors.initials: N
authors.lastname: Ait-Daoud
authors.forename: Henri-Jean
authors.initials: HJ
authors.lastname: Aubin
authors.forename: Wim
authors.initials: W
authors.lastname: Van Den Brink
authors.forename: Richard
authors.initials: R
authors.lastname: Guzzetta
authors.forename: John
authors.initials: J
authors.lastname: Loewy
authors.forename: Bernard
authors.initials: B
authors.lastname: Silverman
authors.forename: Elliot
authors.initials: E
authors.lastname: Ehrich
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000188:drug therapy*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D004341:Drug Evaluation / Q000379:methods; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D008297:Male; D009271:Naltrexone / Q000008:administration & dosage* / Q000009:adverse effects*; D010865:Pilot Projects
chemical_list: D003692:Delayed-Action Preparations; D009271:Naltrexone