title: Extended-release intramuscular naltrexone.
abstract: An extended-release intramuscular formulation of naltrexone that provides sustained release of the drug over a 28-day period has been developed with the aim of improving treatment adherence in patients treated with naltrexone for alcohol dependence. Biodegradable polylactide-co-glycolide polymer microspheres containing 34% w/w naltrexone are reconstituted in an aqueous suspension just prior to intramuscular administration. Extended-release intramuscular naltrexone 380 mg administered once every 4 weeks, in combination with psychosocial therapy, demonstrated superior efficacy to placebo plus psychosocial therapy in reducing the heavy drinking event rate (primary endpoint) in adult patients with alcohol dependence in a 6-month well controlled trial. Among the subset of patients who abstained completely from drinking during the 7 days prior to the first dose of medication (n = 53; 8% of the total study population), those treated with extended-release intramuscular naltrexone 380 mg had greater reductions in the number of drinking days and the number of heavy drinking days compared with placebo recipients. Treatment with extended-release intramuscular naltrexone 380 mg once every 4 weeks for up to 18 months was generally well tolerated, with infrequent treatment-related serious adverse events. The most common treatment-emergent adverse events leading to treatment discontinuation were nausea, injection site reaction and headache. The proportion of patients with clinically significant plasma transaminase elevations was not different between patients receiving extended-release intramuscular naltrexone and those receiving placebo.
authors.affiliation: Adis International Limited, Auckland, New Zealand.
authors.forename: Tracy
authors.initials: T
authors.lastname: Swainston Harrison
authors.forename: Greg L
authors.initials: GL
authors.lastname: Plosker
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Keam
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000188:drug therapy*; D000818:Animals; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007273:Injections, Intramuscular; D009271:Naltrexone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D009325:Nausea / Q000139:chemically induced
chemical_list: D003692:Delayed-Action Preparations; D009292:Narcotic Antagonists; D009271:Naltrexone