Safety concerns with the Centers for Disease Control opioid calculator – free full-text article /PMC5739114/ – 2017 Dec
Morphine milligram equivalence (MME) and other comparable acronyms have been employed in federal pain guidelines and used by policy makers to limit opioid prescribing
On March 18, 2016, the Centers for Disease Control (CDC) released its Guideline for Prescribing Opioids for Chronic Pain.
The guidelines provided 12 recommendations for “primary care clinicians prescribing opioids for chronic pain outside of active cancer treatment, palliative care, and end-of-life care”.
One of the CDC recommendations states that clinicians “should avoid increasing dosage to ≥90 MME/day or carefully justify a decision to titrate dosage to ≥90 MME/day”.
There has been controversy regarding the methodology used to develop the CDC opioid prescribing guidelines,6,7 including concern regarding the bias of the guideline committees due to its domination by the anti-opioid group, Physicians for Responsible Opioid Prescribing
The CDC used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework for producing evidence-based recommendations; however, the guidelines deviated significantly from the established GRADE methodology without associated justification
There is a significant mismatch in the strength of the recommendations made in the guidelines and the supporting evidence
When considering that all recommendations were based on level 3 or 4 evidence yet eleven of the recommendations were assigned grade A, this is a major deviation from the National Clearing House guidelines on levels of evidence and grades of recommendations
The CDC guidelines excluded studies with observation periods of less than 1 year for basing their recommendations on the benefits and risks of opioids.
According to the CDC guidelines, “No evidence shows a long-term benefit of opioids in pain and function versus no opioids for chronic pain with outcomes examined at least 1 year later”.
This is inconsistent with current standards on analgesic study durations in chronic pain. The international harmonized standards adopted by the United States for approval of chronic pain interventions recommend 12 weeks for efficacy assessment.
Tayeb et al conducted a review evaluating analgesic trial durations for opioids, antidepressants, anticonvulsants, nonsteroidal anti-inflammatory drugs, and behavioral therapy
The authors found that nearly all trials had active treatment durations of 12 weeks or less across 869 articles.
Commenting on CDC’s recommendation on nonopioid therapies, Tayeb et al wrote, “if a one year minimum threshold for duration of active treatment were required to justify using any of the major typical therapies for chronic pain, then none of these nonopioid therapies could be recommended.
CDC MME calculator
Along with the strategies employed by MME prescribing thresholds, the CDC provided a checklist for opioid prescribing, along with additional tools to guide clinicians on implementing the recommendations
These tools include the CDC’s “Opioid Guide App” for smartphone.
The App includes an MME calculator requiring the user to enter different opioid(s) along with the daily dose to calculate the total MME daily dose.
The App provides recommendations based on the calculated MME. For 50–89 MME/day, a message appears stating “For ≥50 MME/day, use extra precautions and reassess pain and function more frequently. Discuss reducing dose or tapering/discontinuing opioids if benefits do not outweigh harms”
For ≥90 MME, a message appears stating, “Caution: ≥90 MME may increase risk for overdose. Avoid or carefully justify doses >90 MME/day; consider referring to specialist and schedule reassessment at least every 3 months”
While we agree with the intended concept to improve safety, there are conspicuous flaws in the posted calculator that could significantly affect safety and incur increased risk of mortality and morbidity.
The case with methadone
A major flaw with the CDC calculator is the methadone to morphine conversion, as the conversion is neither linear nor bidirectional due to the unique and complex pharmacokinetics of methadone.
The case with tapentadol
Another flaw of the CDC calculator is the proposed MME for tapentadol. According to the CDC calculator, tapentadol 100 mg has an MME of 40.
Tapentadol is a centrally acting analgesic with dual mechanisms, mu-receptor agonism and norepinephrine reuptake inhibition. Because of its dual mechanisms, the equianalgesic dosing found in clinical trials should not be used to predict nonanalgesic effects such as respiratory depression.
Tapentadol is 18 times less potent than morphine for mu-opioid receptor activation, but only 2–3 times less potent in providing analgesia.
The disparity between tapentadol’s affinity and analgesic potency is presumably due to its activity on norepinephrine reuptake inhibition, which is involved in descending pain modulation.
Tapentadol’s activity on norepinephrine targets neuropathic pain, and it accordingly carries US Food and Drug Administration approval for treatment of pain related to diabetic peripheral neuropathy
Based on mu-receptor potency, tapentadol’s MME for non-analgesic effects related to opioid receptor activation, such as respiratory depression, would be less than equianalgesic doses determined through clinical trials; therefore, applying this equianalgesic dose conversion when switching from tapentadol to a traditional opioid agonist (eg, morphine, hydrocodone, oxycodone) will yield higher opioid receptor activation and increased respiratory depression.
For this reason, the CDC calculator MME for tapentadol represents a major safety issue if used when converting to or from tapentadol
MME dosing was designed in an attempt to examine opioids with similar analgesic effects and should not be used to determine an exact mathematical dosing conversion.
The pharmacology and unique properties of each opioid and patient individuality must be considered when a therapeutic opioid conversion is contemplated.
Conversion should not simply rely on a mathematical formula embedded within the CDC calculator software.
Indeed, this is just part of the drive toward healthcare by standardization and algorithms: machines will diagnose and treat us instead of humans.
We expect a higher level of scientific accuracy and integrity from an agency entrusted to protect citizens’ health and welfare.