The acceptability, safety and tolerability of combined methadone-naloxone in methadone maintained individuals aged between 18 - 65

The acceptability, safety and tolerability of combined methadone-naloxone: Is oral methadone-naloxone indistinguishable from mono-methadone? Does injection of methadone-naloxone precipitate withdrawal? Robert Graham, Suzanne Rizzo, Kristy Korompay, James Bell Introduction: Daily methadone and buprenorphine dosing is associated with high costs and rigidity. Maintenance models that predominantly employ dispensed medication (i.e. unsupervised dosing) may be more cost effective and preferable to clients and health departments. However, takeaway doses are often used in unintended ways including being injected by the client or other persons. The addition of naloxone to methadone has the potential to discourage the diversion of takeaway doses. Aims: To ascertain the safety and tolerability of oral methadone-naloxone in a 50:1 ratio by investigating aspects of its pharmacokinetic and pharmacodynamic properties, and in a second study, to investigate the effectiveness of the combination in precipitating withdrawal when administered intramuscularly. Methods: A randomised phase II study, double-blind, crossover design was used for the oral study. 10 subjects attending methadone clinics who were on a stable dose of least 20mg methadone volunteered and were given either methadone-naloxone or methadone alone for 14 days and then switched to the alternative for a total of 28 day study period. The second study was a Phase II, single group before-after design. Five of the subjects from the first study were administered IM saline solution followed by IM 10mg methadone/0.2mg naloxone prior to their scheduled methadone dose and were observed for 60 minutes. In the absence of objective signs of withdrawal at 30 minutes, participants were administered an additional 20mg methadone/0.4mg naloxone intramuscularly and observed for a further 60 minutes. Findings: Oral methadone naloxone in a 50:1 ratio appeared to be well tolerated. The same preparation reliably precipitated opioid withdrawal upon injection among methadone maintained individuals.