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Morphine Equivalent Dose (MED) - Opioid Conversions
Morphine Milligram Equivalents (MME)

Updated 2022 CDC Guidelines


Morphine Milligram Equivalents Calculator

The Morphine Milligram Equivalent Dose (MED) conversions calculator

The MED calculator allows a clinician to generate an equivalent dose of morphine for a patient taking one or more common opioids.

Published equianalgesic ratios are considered crude estimates at best; therefore, it is imperative that careful consideration is given to individualizing the dose of the selected opioid. Dosage titration of the new opioid should be completed slowly and with frequent monitoring.  Conversion ratios in many equianalgesic dosing tables do not apply to repeated doses of opioids.

The amount of residual drug in the patient's system must be accounted for
. Example: fentanyl will continue to be released from the skin 12 to 36 hours after removal of the patch. Residual effects from discontinued long-acting formulations should also be assessed before converting a patient to a new opioid.

Converting From:

Codeine (PO) (Daily dose in mg)
Fentanyl (Transdermal) (mcg/hr)
Hydrocodone (PO) (Daily dose in mg)
Hydromorphone (PO) (Daily dose in mg)
METHadone (PO) 
[ ? ]Additional options available near the bottom of the page.
(Daily dose in mg)
MORPHine (PO) (Daily dose in mg)
Oxycodone (PO) (Daily dose in mg)
Oxymorphone (PO) (Daily dose in mg)
Tapentadol (PO) (Daily dose in mg)
Tramadol (PO) (Daily dose in mg)

Morphine Milligram Equivalents


Please review these important points:

  1. Published equianalgesic ratios are considered crude estimates at best and therefore it is imperative that careful consideration is given to individualizing the dose of the selected opioid. Dosage titration of the new opioid should be completed slowly and with frequent monitoring. 
  2. Conversion ratios in many equianalgesic dosing tables do not apply to repeated doses of opioids.
  3. The amount of residual drug in the patient's system must be accounted for. Example: fentanyl will continue to be released from the skin 12 to 36 hours after removal of the patch. Residual effects from discontinued long-acting formulations should also be assessed before converting a patient to a new opioid.
  4. Review the concept of incomplete cross-tolerance:
  5. D. McAuley:   "Incomplete cross-tolerance relates to tolerance to a currently administered opiate that does not extend completely to other opioids. This will tend to lower the required dose of the second opioid. This incomplete cross-tolerance exists between all of the opioids and the estimated difference between any two opiates could vary widely. This points out the inherent dangers of using an equianalgesic table and the importance of viewing the tabulated data as approximations. Many experts recommend - depending on age and prior side effects - reducing the dose of the new opiate by 33 to 50 percent to account for this incomplete cross-tolerance. (Example: a patient is receiving 200mg of oral morphine daily (chronic dosing), however, because of side effects a switch is made to oral hydromorphone 25 - 35mg daily - (this represents a 33 to 50 percent reduction in dose compared to the calculated 50mg conversion dose produced via the equianalgesic calculator). This new regimen can then be re-titrated to patient response. In all cases, repeated comprehensive assessments of pain are necessary in order to successfully control the pain while minimizing side-effects."
  6. The use of high but ineffective doses of a previous opioid may result in overestimation of the converted opioid. 
The authors make no claims of the accuracy of the information contained herein; and these suggested doses and/or guidelines are not a substitute for clinical judgment. PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER. 











Background:


 

CDC Clinical Practice Guideline for Prescribing Opioids for Pain - United States, 2022:

Source:
CDC Clinical Practice Guideline for Prescribing Opioids for Pain — United States, 2022 | MMWR     |   Table

TABLE. Morphine milligram equivalent doses for commonly prescribed opioids for pain management
Opioid Conversion factor*
Codeine 0.15
Fentanyl transdermal (in mcg/hr) 2.4
Hydrocodone 1.0
Hydromorphone 5.0
Methadone 4.7
Morphine 1.0
Oxycodone 1.5
Oxymorphone 3.0
Tapentadol 0.4
Tramadol§ 0.2

Sources: Adapted from Von Korff M, Saunders K, Ray GT, et al. Clin J Pain 2008;24:521–7 and Nielsen S, Degenhardt L, Hoban B, Gisev N. Pharmacoepidemiol Drug Saf 2016;25:733–7.


Abbreviations: mcg/hr = microgram per hour; mg = milligram; MME = morphine milligram equivalent.
* Multiply the dose for each opioid by the conversion factor to determine the dose in MMEs. For example, tablets containing hydrocodone 5 mg and acetaminophen 325 mg taken four times a day would contain a total of 20 mg of hydrocodone daily, equivalent to 20 MME daily; extended-release tablets containing oxycodone 10 mg and taken twice a day would contain a total of 20 mg of oxycodone daily, equivalent to 30 MME daily. The following cautions should be noted: 1) All doses are in mg/day except for fentanyl, which is mcg/hr. 2) Equianalgesic dose conversions are only estimates and cannot account for individual variability in genetics and pharmacokinetics. 3) Do not use the calculated dose in MMEs to determine the doses to use when converting one opioid to another; when converting opioids, 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. 4) 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. 5) Use particular caution with transdermal fentanyl because it is dosed in mcg/hr instead of mg/day, and its absorption is affected by heat and other factors. 6) Buprenorphine products approved for the treatment of pain are not included in the table because of their partial µ-receptor agonist activity and resultant ceiling effects compared with full µ-receptor agonists. 7) These conversion factors should not be applied to dosage decisions related to the management of opioid use disorder.


 Tapentadol is a µ-receptor agonist and norepinephrine reuptake inhibitor. MMEs are based on degree of µ-receptor agonist activity; however, it is unknown whether tapentadol is associated with overdose in the same dose-dependent manner as observed with medications that are solely µ-receptor agonists.


§  Tramadol is a µ-receptor agonist and norepinephrine and serotonin reuptake inhibitor. MMEs are based on degree of µ-receptor agonist activity; however, it is unknown whether tramadol is associated with overdose in the same dose-dependent manner as observed with medications that are solely µ-receptor agonists.

 



Implications:

Dunn et al. (direct quotes)
Results: Fifty-one opioid-related overdoses were identified, including six deaths.

  • Compared to patients receiving 1-20mg of opioids per day (0.2% annual overdose rate), patients receiving 50-99 mg had a 3.7 fold increase in overdose risk (95% C.I. 1.5, 9.5) and a 0.7% annual overdose rate.
  • Patients receiving 100mg or more per day had an 8.9 fold increase in overdose risk (95% C.I. 4.0, 19.7) and a 1.8% annual overdose rate.

Dunn KM, Saunders KW, Rutter CM, et al. Opioid Prescriptions for Chronic Pain and Overdose: A Cohort Study. Ann Intern Med. 2010;152:85–92. doi: https://doi.org/10.7326/0003-4819-152-2-201001190-00006


Bohnert AS et al. (direct quotes)
 In a ROC analysis, dosage was a moderately good “predictor” of opioid overdose death, indicating that, on average, overdose cases had a prescribed opioid dosage higher than 71% of controls.

Conclusions: A clear cut-point in opioid dosage to distinguish between overdose cases and controls was not found. However, lowering the recommended dosage threshold below the 100 MEM used in many recent guidelines would affect proportionately few patients not at risk for overdose while potentially benefitting many of those at risk for overdose.

These studies found increases in risk starting at dosages above 20 morphine-equivalent milligrams (MEM) per day, with dramatic increases in overdose rates for patients prescribed 100 MEM per day or greater. In the absence of evidence that patients gain benefit from higher dosage prescribing,8 these findings have led to a reconsideration of whether there is a threshold beyond which patients’ dosages should not be escalated.

Thus, lower prescribed opioid dosages are associated with reduced risk of overdose, but risk is not completely absent at low dosages. More specifically, there is not a threshold below which risk is eliminated, and clinicians should be aware that there are risks of opioid overdose even at lower dosages.

Bohnert AS, Logan JE, Ganoczy D, Dowell D. A Detailed Exploration Into the Association of Prescribed Opioid Dosage and Overdose Deaths Among Patients With Chronic Pain. Med Care. 2016 May;54(5):435-41. doi: 10.1097/MLR.0000000000000505. PMID: 26807540; PMCID: PMC6626611.




Implications:

Dunn et al. (direct quotes)
Results: Fifty-one opioid-related overdoses were identified, including six deaths.

  • Compared to patients receiving 1-20mg of opioids per day (0.2% annual overdose rate), patients receiving 50-99 mg had a 3.7 fold increase in overdose risk (95% C.I. 1.5, 9.5) and a 0.7% annual overdose rate.
  • Patients receiving 100mg or more per day had an 8.9 fold increase in overdose risk (95% C.I. 4.0, 19.7) and a 1.8% annual overdose rate.

Dunn KM, Saunders KW, Rutter CM, et al. Opioid Prescriptions for Chronic Pain and Overdose: A Cohort Study. Ann Intern Med. 2010;152:85–92. doi: https://doi.org/10.7326/0003-4819-152-2-201001190-00006


Bohnert AS et al. (direct quotes)
 In a ROC analysis, dosage was a moderately good “predictor” of opioid overdose death, indicating that, on average, overdose cases had a prescribed opioid dosage higher than 71% of controls.

Conclusions: A clear cut-point in opioid dosage to distinguish between overdose cases and controls was not found. However, lowering the recommended dosage threshold below the 100 MEM used in many recent guidelines would affect proportionately few patients not at risk for overdose while potentially benefitting many of those at risk for overdose.

These studies found increases in risk starting at dosages above 20 morphine-equivalent milligrams (MEM) per day, with dramatic increases in overdose rates for patients prescribed 100 MEM per day or greater. In the absence of evidence that patients gain benefit from higher dosage prescribing,8 these findings have led to a reconsideration of whether there is a threshold beyond which patients’ dosages should not be escalated.

Thus, lower prescribed opioid dosages are associated with reduced risk of overdose, but risk is not completely absent at low dosages. More specifically, there is not a threshold below which risk is eliminated, and clinicians should be aware that there are risks of opioid overdose even at lower dosages.

Bohnert AS, Logan JE, Ganoczy D, Dowell D. A Detailed Exploration Into the Association of Prescribed Opioid Dosage and Overdose Deaths Among Patients With Chronic Pain. Med Care. 2016 May;54(5):435-41. doi: 10.1097/MLR.0000000000000505. PMID: 26807540; PMCID: PMC6626611.


CDC Guidelines:   (direct quotes)
Higher dosages of opioids are associated with higher risk of overdose and death- even relatively low dosages (20-50 morphine milligram equivalents (MME) per day) increase risk. Higher dosages haven’t been shown to reduce pain over the long term. One randomized trial found no difference in pain or function between a more liberal opioid dose escalation strategy (with average final dosage 52 MME) and maintenance of current dosage (average final dosage 40 MME).

Calculating the total daily dose of opioids helps identify patients who may benefit from closer monitoring, reduction or tapering of opioids, prescribing of naloxone, or other measures to reduce risk of overdose.

Dosages at or above 50 MME/day increase risks for overdose by at least  2x the risk at <20 MME/day.

Clinicians should avoid prescribing opioid pain medication and benzodiazepines concurrently whenever possible (recommendation category: A, evidence type: 3).
Benzodiazepines and opioids both cause central nervous system depression and can decrease respiratory drive. Concurrent use is likely to put patients at greater risk for potentially fatal overdose.

Do not use the calculated dose in MMEs to determine dosage for converting one opioid to another - the new opioid should be lower to avoid unintentional overdose caused by incomplete cross-tolerance and individual differences in opioid pharmacokinetics.

Sources:
.
https://www.cdc.gov/mmwr/volumes/65/rr/rr6501e1.htm


Dasgupta N et al.   (direct quotes)
Mortality rates increased gradually across the range of average daily milligrams of morphine equivalents. 80.0% of opioid analgesic patients also received benzodiazepines. Rates of overdose death among those co-dispensed benzodiazepines and opioid analgesics were ten times higher (7.0 per 10,000 person-years, 95 percent CI: 6.3, 7.8) than opioid analgesics alone (0.7 per 10,000 person years, 95 percent CI: 0.6, 0.9).

Dasgupta N, Funk MJ, Proescholdbell S, Hirsch A, Ribisl KM, Marshall S. Cohort Study of the Impact of High-Dose Opioid Analgesics on Overdose Mortality. Pain Med. 2016 Jan;17(1):85-98.



References
  1. American Pain Society (APS). Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain, 6th edition. 2008. Glenview, IL 60025. 
  2. Ayonrinde OT, Bridge DT. The rediscovery of methadone for cancer pain management. Med J Aust 2000; 173(10): 536-540.
  3. Breitbart W, Chandler S, Eagel B, et al. An alternative algorithm for dosing transdermal fentanyl for cancer-related pain. Oncology. 2000;14:695-705.
  4. Donner B, et al. Direct conversion from oral morphine to transdermal fentanyl. Pain. 1996; 64:527-534.
  5. Duragesic Package Insert:      Accessed: October 2010.
  6. Fisch MJ, Cleeland CS: Managing cancer pain. In: Skeel RT, ed.: Handbook of Cancer Chemotherapy. 6th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2003, pp 663. 
  7. Friedman LL, Rodgers PE. Pain management in palliative care. Clin Fam Prac. 2004;6:371-393.
  8. Fudin J, Marcoux MD, Fudin JA.  Mathematical Model For Methadone Conversion Examined. Practical Pain Management. 2012(Sep):46-51. Link to article. [Fudin Factor graphically compared to Ripamonte, Ayonrinde, and Mercadante - jpeg]. [Additional information regarding methadone from Dr. Fudin.
  9. Gazelle G, Fine PG. Fast Facts Documents #075 - Methadone for the Treatment of Pain, 2nd ed 2009. End of Life/ Palliative Education Resource Center. Link: https://www.eperc.mcw.edu/EPERC/FastFactsIndex/ff_075.htm (Revisited April 2013).
  10. Methadone PI (package insert). Dolophine hydrochloride, 5 mg, 10mg tablets. July 2012.
  11. McPherson ML. Demystifying opioid conversion calculations. A guide for effective dosing. Bethesda: American Society of Health System Pharmacists;2010. [pp107-143]
  12. Mercadante S, Casuccio A, Fulfaro F, et al. Switching from morphine to methadone to improve analgesia and tolerability in cancer patients: A prospective study. J Clin Oncol. 2001;19:2898-2904.
  13. Morley J, Makin M. The use of methadone in cancer pain poorly responsive to other opiates. Pain Rev.1998;5:51-58.
  14. Ripamonti C, Groff L, Brunelli C, Polastri D, Stavrakis A, De Conno F. Switching from morphine to oral methadone in treating cancer pain: what is the equianalgesic dose ratio? J Clin Oncol. 1998;16(10):3216-3221.
CDC Updated 2022 Morphine Milligram Equivalents Calculator

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