What are the morphine equivalents for methadone and hydromorphone?

Morphine Equivalents for Methadone and Hydromorphone

Hydromorphone Conversion

Hydromorphone converts to morphine at a ratio of 4:1 to 5:1, meaning 1 mg of hydromorphone equals approximately 4-5 mg of oral morphine. 1

• The CDC guidelines specify a conversion factor of 4 for hydromorphone, so multiply the hydromorphone dose by 4 to calculate morphine milligram equivalents (MME). 1
• The ESMO guidelines cite a range of 1:5 to 1:7.5 (hydromorphone to morphine) based on randomized controlled trial data. 1
• For practical purposes, use the 1:4 ratio for most clinical conversions, as this is the most widely accepted standard. 1

Important caveat: Hydromorphone metabolites may be more neurotoxic than morphine metabolites, potentially causing myoclonus, hyperalgesia, and seizures, particularly in patients with renal insufficiency. 1

Methadone Conversion

Methadone conversion is complex and dose-dependent, with ratios ranging from 4:1 at low doses to 12:1 or higher at doses exceeding 100 mg/day. 1, 2

Dose-Dependent Conversion Ratios (Morphine to Methadone):

• 1-20 mg/day methadone: Use a 4:1 ratio (morphine:methadone) 1, 2
• 21-40 mg/day methadone: Use an 8:1 ratio 1, 2
• 41-60 mg/day methadone: Use a 10:1 ratio 1
• ≥61-80 mg/day methadone: Use a 12:1 ratio 1
• >100 mg/day methadone: May require ratios exceeding 12:1 2

Critical Safety Considerations:

Never use these conversion ratios in reverse (converting FROM methadone TO other opioids) due to methadone's long and unpredictable half-life (8 to >120 hours) and risk of accumulation. 1, 2

• When switching FROM methadone to another opioid, use a conservative 1:1 ratio initially, with frequent dose adjustments as methadone clears from the system. 2
• Research demonstrates that when rotating from IV methadone to other opioids, the ratio is approximately 1:13.5 (methadone:morphine equivalent), while oral methadone is approximately 1:4.7. 3

Methadone Initiation Guidelines:

• Start methadone at doses lower than calculated and titrate slowly upward due to high inter-individual pharmacokinetic variability. 1
• Provide adequate short-acting breakthrough pain medications during the titration period. 1
• The ESMO guidelines recommend reducing the calculated equianalgesic dose by one-fourth to one-twelfth when switching TO methadone. 1
• Some experts suggest using 1/5 of the previous morphine dose as a loading dose, particularly for patients with poor pain control. 1

Monitoring Requirements:

• Methadone doses ≥100-120 mg/day may cause QTc prolongation and torsades de pointes. 1
• Obtain baseline and follow-up electrocardiograms for patients on methadone doses >100 mg/day. 1
• Consult a pain management specialist if unfamiliar with methadone prescribing or if rapid switching is required. 1

Common Pitfalls

The greatest variability in opioid conversions exists with fentanyl and methadone, where standard deviations in clinical practice are extremely large. 4

• Equianalgesic conversions are estimates only and cannot account for individual genetic and pharmacokinetic variability. 1
• When converting between opioids, dose the new opioid substantially lower than the calculated MME to avoid accidental overdose due to incomplete cross-tolerance. 1
• Both hydromorphone and morphine should be used with extreme caution in patients with fluctuating renal function due to accumulation of renally cleared metabolites that cause neurologic toxicity. 1