What are morphine milliequivalents (MME), how are they calculated, and what are the recommended dosing limits?

Morphine Milligram Equivalents (MME): Definition, Calculation, and Clinical Application

What MME Represents

Morphine milligram equivalents (MME) is a standardized metric that converts different opioid medications and doses into an equivalent amount of morphine, allowing clinicians to calculate total daily opioid burden for risk assessment, monitor cumulative exposure across multiple prescriptions, and identify patients at higher risk for overdose. 1

How to Calculate MME

To determine MME, multiply the total daily dose of each opioid by its specific conversion factor 2, 3:

Standard Conversion Factors

• Morphine: 1.0 2, 3
• Oxycodone: 1.5 2, 1, 3
• Hydrocodone: 1.0 2, 3
• Hydromorphone: 5.0 2, 3
• Fentanyl transdermal (mcg/hr): 2.4 2, 3
• Codeine: 0.15 2, 3
• Methadone: 4.7 2, 3
• Tramadol: 0.2 2, 3
• Tapentadol: 0.4 2, 3

Calculation Example

For a patient taking hydrocodone 5 mg with acetaminophen 325 mg four times daily: 20 mg total daily hydrocodone × 1.0 conversion factor = 20 MME/day 2

For extended-release oxycodone 10 mg twice daily: 20 mg total daily oxycodone × 1.5 conversion factor = 30 MME/day 2

Critical Dosing Thresholds

The 50 MME/Day Threshold

Before increasing total opioid dosage to ≥50 MME/day, clinicians must pause and carefully reassess evidence of individual benefits and risks. 2, 3

• Many patients do not experience benefit in pain or function from increasing opioid dosages to ≥50 MME/day but are exposed to progressive increases in risk as dosage increases 2, 3
• At or above 50 MME/day, implement additional precautions including increased frequency of follow-up and considering offering naloxone 3
• If increasing dosage, use caution and increase by the smallest practical amount 2, 3

The 90 MME/Day Threshold

Clinicians should avoid increasing dosages to ≥90 MME/day or must carefully justify such decisions based on diagnosis, incremental benefits for pain and function relative to harms, other treatments and effectiveness, and recommendations from pain specialists. 3

• Doses ≥90 MME/day are associated with progressively increased overdose risk 3
• If patients do not experience improvement in pain and function at ≥90 MME/day, or if there are escalating dosage requirements, clinicians should discuss other approaches to pain management and consider tapering 3

Starting Doses

Clinicians should start opioids at the lowest effective dosage, typically equivalent to 20-30 MME/day for opioid-naïve patients 3

The Most Dangerous Pitfall: Bidirectional Use of Conversion Factors

MME calculations are for risk assessment only—never use these conversion factors to determine doses when switching from one opioid to another. 2, 1, 3, 4

Why This Matters

• Conversion factors are estimates only and cannot account for individual variability in genetics and pharmacokinetics 2, 1
• When rotating between opioids, the new opioid should be dosed at 25-50% lower than the calculated equianalgesic dose to avoid accidental overdose due to incomplete cross-tolerance 1, 4
• The 1.5 conversion factor tells you how much morphine equivalence you're prescribing, but it should never be used in reverse to calculate a new opioid dose when switching medications 1

Proper Opioid Rotation Protocol

When converting between opioids 1, 4:

1. Calculate the equianalgesic dose using conversion factors
2. Always reduce by 25-50% from the calculated dose
3. If pain was well-controlled on the previous opioid, use a 50% reduction 4
4. If pain was poorly controlled, may use only a 25% reduction but monitor closely 4
5. Reassess pain control and side effects within 24-48 hours 4

Special Cautions for Specific Opioids

Methadone

Use particular caution with methadone dose conversions because methadone has a long and variable half-life, and peak respiratory depressant effect occurs later and lasts longer than peak analgesic effect 2, 3, 4

Transdermal Fentanyl

• Fentanyl is dosed in mcg/hr instead of mg/day 2, 3
• Its absorption is affected by heat and other factors 2, 3
• Use particular caution when calculating MME for transdermal fentanyl 2

Buprenorphine

Buprenorphine products approved for pain treatment are not included in standard MME conversion tables because of their partial μ-receptor agonist activity and resultant ceiling effects compared with full μ-receptor agonists 2

Clinical Context and Limitations

Primary Purpose of MME

The CDC established these conversion factors primarily for 1:

• Calculating total daily opioid burden for risk assessment
• Monitoring cumulative opioid exposure across multiple prescriptions
• Identifying patients at higher risk for overdose (particularly at ≥50 MME/day and ≥90 MME/day thresholds)

Not an Inflexible Standard

The recommendations related to opioid dosages are not intended to be used as an inflexible, rigid standard of care; rather, they are intended to be guideposts to help inform clinician-patient decision-making 2, 3

Variability in Practice

Despite standardized conversion factors, significant variation exists in how clinicians perform opioid conversions, particularly for fentanyl and methadone, as evidenced by large standard deviations in clinical practice 5