What is the equivalent dose of methadone for 1 milligram (mg) of oral morphine?

From the Guidelines

Converting 1 mg of oral morphine to methadone requires careful consideration and individualized assessment, as the conversion ratio can vary from 1:5 to 1:12, and a direct conversion is not recommended without clinical judgment. The conversion between these opioids is complex and not a simple mathematical calculation, as methadone has a long half-life, unpredictable potency ratio that varies with dose, and significant risk for QT prolongation and respiratory depression 1. When converting from morphine to methadone, clinicians typically use variable conversion ratios based on the patient's total daily morphine dose, with higher morphine doses requiring relatively less methadone. For example, at low morphine doses, the ratio might be 3:1 (morphine:methadone), while at higher doses it could be 10:1 or more 1.

Some key points to consider when converting from morphine to methadone include:

• The conversion ratio can vary from 1:5 to 1:12, and a direct conversion is not recommended without clinical judgment 1
• Methadone has a long and variable half-life, and peak respiratory depressant effect occurs later and lasts longer than peak analgesic effect 1
• The new opioid is typically dosed at a substantially lower dose than the calculated MME dose to avoid overdose because of incomplete cross-tolerance and individual variability in opioid pharmacokinetics 1
• Methadone conversion should involve a gradual transition with close monitoring, typically reducing the calculated methadone dose by 25-50% initially to account for incomplete cross-tolerance 1

Given the complexity and risks associated with converting from morphine to methadone, this conversion should only be performed by healthcare providers experienced in pain management or addiction medicine, with careful consideration of the patient's medical history, concurrent medications, and monitoring capabilities. Additionally, the most recent guidelines from 2022 emphasize the importance of caution when converting opioids, particularly with methadone, due to its long and variable half-life and significant risk for respiratory depression 1.

From the Research

Conversion of Oral Morphine to Methadone

• There is no direct evidence provided in the given studies to support a specific conversion ratio from 1 mg of oral morphine to methadone 2, 3, 4, 5, 6.
• The study by 2 discusses the conversion of opioid regimens to methadone but does not provide a specific conversion ratio for oral morphine to methadone.
• Other studies focus on the pharmacology and abuse liability of oxycodone 3, sublingual absorption of opioid analgesics 4, uniform assessment and ranking of opioid μ receptor binding constants 5, and the use of buprenorphine for chronic pain management 6, but do not provide relevant information for converting oral morphine to methadone.

Available Information on Opioid Conversion

• The lack of concrete guidance on converting opioid regimens to methadone is acknowledged in the study by 2, highlighting the challenges faced by clinicians in community settings.
• The study by 4 provides information on the sublingual absorption of methadone, but this is not directly relevant to converting oral morphine to methadone.
• The study by 5 provides information on the binding affinity of various opioid drugs, including methadone and morphine, but does not provide a conversion ratio.

Limitations

• The available studies do not provide sufficient information to support a specific conversion ratio from 1 mg of oral morphine to methadone.
• Clinicians may need to consult other resources or expert opinions to determine the appropriate conversion ratio for their patients.