Methadone pharmacology and induction

Methadone pharmacology and induction
Methadone is a synthetic long acting mu receptor agonist suitable for the treatment of opioid use disorder. Methadone has a longer plasma half life than morphine (average 22 hours (15-32 hours) vs 2 hours for morphine) which permits once daily supervised dosing. Methadone is well absorbed after oral administration with a peak effect after four hours and does cross the blood-brain barrier. It is thought that 20 to 50 mg daily of Methadone usually prevents opiate withdrawal phenomena and doses of > 60 mg prevents the euphoria from additional use of unsanctioned opioids.

Regardless of previous opiate or opioid usage the same low starting dose of methadone is prescribed. Starting doses of Methadone are usually between 20-30mg daily with higher risks patients starting at 20mg daily and doses can be up-titrated every 3-5 days based on clinical need. It is important to remember that it takes 5 half lives for Methadone to reach steady state in plasma. Methadone has a half life of approximately one day and thus half of each day's dose remains in the body and is added to the next day's new dose. Serum methadone levels will continue to rise (which can reach dangerous levels if doses are excessive) until steady state is achieved. It can take 5 days for Methadone to reach a steady state in plasma and can take 10 days for Methadone to equilibrate between plasma and body tissues.

Causes of Methadone overdose include:
• Single overdose
• Starting dose too high
• Accidental ingestion
• Accumulated toxicity
• Rapid induction
• Polypharmacy
• Hypnosedative combinations -benzodiazepines etc
• Reduced opioid tolerance
• Low neuroadaptation
• Comorbidity

Safety principles to consider when prescribing Methadone include:
• Risk of overdose highest in the first two weeks of treatment
• Safety principle: Start low and go slow
• No cross tolerance with other opioids
• Same low starting dose irrespective of previous opioid burden
• Never increase dose without a face-to-face review
• Usual practice to review patient weekly and increase the dose weekly
• Can take 6-8 weeks to achieve stability
• Cease other illicit and prescribed opioids / hypno-sedatives

Author: Dr Thileepan Naren
Thileepan is an Addiction Medicine Advanced Trainee and experienced general practitioner with a demonstrated history of working with disadvantaged and marginalized groups.