What is the recommended starting dose of methadone (opioid agonist) for a patient who has missed 5 days of treatment?

Methadone Reinitiation After 5-Day Lapse

After missing 5 days of methadone treatment, restart at 20-30 mg as a single supervised dose, not exceeding 30 mg on day one, because loss of tolerance occurs after more than 5 days without opioids and the previous maintenance dose poses significant overdose risk. 1

Critical Safety Principle

Loss of tolerance must be assumed in any patient who has not taken opioids for more than 5 days. 1 This is the most important consideration—your patient has essentially lost their opioid tolerance and must be treated as opioid-naive, regardless of their previous maintenance dose.

Specific Reinitiation Protocol

Day 1 Dosing

• Initial dose: 20-30 mg administered under direct supervision 1
• Maximum day 1 dose: 40 mg total (including any same-day adjustments) 1
• Administer when withdrawal symptoms are present but patient shows no signs of sedation or intoxication 1

Same-Day Adjustments (if needed)

• Wait 2-4 hours after initial dose for peak levels to be reached 1
• If withdrawal symptoms persist or reappear, may provide additional 5-10 mg 1
• Total first day dose must not exceed 40 mg 1

Subsequent Titration

Week 1 Approach

• Make dose adjustments based on withdrawal control at expected peak activity (2-4 hours post-dose) 1
• Titrate cautiously—deaths have occurred in early treatment due to cumulative effects 1
• Remind patient that doses will "hold" longer as tissue stores accumulate 1

Return to Maintenance Dosing

• Do not use previous maintenance dose to determine reinitiation dose 1
• Previous treatment episodes or prior dose requirements are irrelevant after 5-day lapse 1
• Retitrate toward maintenance range (typically 80-120 mg/day) over subsequent days to weeks, not immediately 1, 2

Key Pharmacokinetic Considerations

Methadone's long half-life (8-59 hours) means steady-state is not reached until 3-5 days of dosing, making early overdose risk particularly high with aggressive dosing 1. The drug accumulates in liver tissue and is slowly released, prolonging effects despite low plasma concentrations 1.

Common Pitfalls to Avoid

• Never restart at the previous maintenance dose—this is the most dangerous error 1
• Do not determine dose based on patient's reported previous dose or illicit drug use history 1
• Avoid same-day dose increases exceeding 10 mg 1
• Do not exceed 40 mg total on day 1 under any circumstances 1

Monitoring Requirements

• Direct observation of first dose administration 1
• Assessment for sedation and respiratory depression at 2-4 hours post-dose 1
• Daily evaluation during first week for withdrawal symptoms and adverse effects 1
• If patient misses 3+ days again during retitration, restart this protocol 3