CDC Clinical Practice Guideline for Prescribing Opioids for Pain -
United States, 2022:
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.
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.
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.
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.
|
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- Donner B, et al. Direct conversion from oral
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- Duragesic Package Insert:
Accessed: October 2010.
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- 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.
- 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).
- Methadone PI (package insert). Dolophine hydrochloride, 5 mg, 10mg tablets.
July 2012.
- McPherson ML. Demystifying opioid conversion
calculations. A guide for effective dosing. Bethesda:
American Society of Health System Pharmacists;2010.
[pp107-143]
- 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.
- Morley J, Makin M. The use of methadone in cancer
pain poorly responsive to other opiates. Pain Rev.1998;5:51-58.
- 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.
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