title: Safety and tolerability of as-needed nalmefene in the treatment of alcohol dependence: results from the Phase III clinical programme.
abstract: OBJECTIVE
  To investigate safety and tolerability of nalmefene for reduction of alcohol consumption in alcohol-dependent patients.
  
  
  METHODS
  Pooled data from three randomized, placebo-controlled studies (two 6-month; one 12-month) of 18 mg nalmefene (as-needed use) in alcohol-dependent patients looking at the total population (placebo n = 824, nalmefene n = 1123) and patients with high/very high drinking risk levels at screening and randomization (target population: placebo n = 374, nalmefene n = 450).
  
  
  RESULTS
  In the study, 62.7% of patients on placebo and 74.7% on nalmefene in the total population had treatment-emergent adverse events (TEAEs). Fourty-seven (5.9%) on placebo and 149 (13.0%) on nalmefene dropped out due to TEAEs. Thirty-five (4.4%) on placebo and 57 (5.0%) on nalmefene had serious adverse events. Tolerability and safety were similar in the target population and total population. Most frequent TEAEs were transient, mainly occurring at treatment initiation. There was no difference in tolerability and safety if nalmefene was taken daily or intermittently; no signal of increased risk of suicide-related behavior with nalmefene. The higher incidence of psychiatric events in the nalmefene group was mainly due to the TEAE of confusional state.
  
  
  CONCLUSIONS
  Although there was a higher incidence of TEAEs and TEAEs leading to dropout, nalmefene was well-tolerated and no major safety issues were identified.
authors: University of Amsterdam, Academic Medical Center, Psychiatry , Meibergdreef 5, Gerrit vd Veenstraat 84-hs, Amsterdam, 1077el , Netherlands w.vandenbrink@amc.uva.nl.
authors: Wim
authors: W
authors: van den Brink
authors: John
authors: J
authors: Strang
authors: Antoni
authors: A
authors: Gual
authors: Per
authors: P
authors: Sørensen
authors: Thomas Jon
authors: TJ
authors: Jensen
authors: Karl
authors: K
authors: Mann
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000517:prevention & control; D000437:Alcoholism / Q000188:drug therapy*; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D009292:Narcotic Antagonists; D009271:Naltrexone; C038981:nalmefene
keywords: adverse events; alcohol dependence; nalmefene; opioid antagonist