HIGH DOSE OPIATES -how dangerous are they? and who can regulate them? #611

A position paper by

JATH Educational Consortium, LLC

Thomas F. Kline MD, PhD
Robert Parangi, MD
Jed Graham, MD
Carolyn Concia, NP

Editor: Leslie Bythewood

High-dose limits make sense. Most medications have FDA (Food and Drug Administration) limits on their doses. When maximum doses are exceeded, toxic reactions and death can occur. This is the reason for dose limits in most all prescription drugs of all kinds. For example, anti-depressants have fixed FDA dose limits; go over the limit and you’re in trouble, putting you at risk of death. This is is not the case with opiate pain medicine because opiate pain medicines have no FDA maximum dose. The same is true for insulin, no maximum dose.

FDA is the only agency designated by Congress to be the regulatory agency for prescription medications, their use, warnings, and dosages.

If there is a danger of death the FDA would have put upper milligram limits on the opioids long ago. The same is true for insulin.

The FDA allows only a few rare drugs to be given without concern for dose: insulin, coumadin (a generic blood thinner) and opiate pain medications. The FDA does not limit the dose of these three medication groups since the medications themselves do not have toxic side effects at any dose, whereas Tylenol, for example, has a maximum-per-day dose of 3000 mg. No opiates are bound by FDA dose limits. No one can interfere. Federal jurisdiction rules.

The Centers for Medicare and Medicaid Services (CMS) and the Centers for Disease Control (CDC) have been engaging in an unauthorized and clinically dangerous practice attempting to overrule FDA no maximum doses. This can be dangerous to patient care leading to harm. To force a patient to adhere to an artificial dose limitation not approved by FDA can lead to under-treatment with lives ruined and lives taken (Google: “medium suicides”). Neither agency has asked the FDA to approve MME cut off doses.

Changing any aspect of a given prescription drug “package insert” (FDA’s print out of all the aspects of the approved drug) requires petitioning the FDA for a change in dose limits. This was actually done in 2012. “Physicians for Responsible Opioid Prescribing” (PROP), an organization founded by Andrew Kolodny, M.D. petitioned the FDA in 2012 for dose restrictions. The FDA denied PROP’s petition (FDA 2012-P-0818) after reviewing PROP’s articles and discrediting them, many of which still are used at CDC and CMS to try to support “high dose causes problems” — which are unfounded.

The reason to mention this process by PROP is the discredited notions were carried over to the CDC where PROP help write the voluntary guidelines using much of the discredited FDA petition claiming it was valid in PROP’s virtual creation of the flawed “Guideline”.

For these reasons, and reasons of our internal analysis, and for reasons of palliative care exemption, we find the CDC guidelines not appropriate for clinical or regulatory use.

This “high dose” fallacy has been repudiated by the AMA (American Medical Association) and the CDC itself (see below). Recent research has shown that less than 2% of all overdoses involve opiate pain medication at any dose. Ninety eight percent of “opioid are in “the street”.

Thomas Frieden, M.D. and the CDC were incorrect. The result is doctors sanctioned by medial Boards, by CMS, and by DEA, for “over-prescribing,” or prescribing “excessive doses of opioids” none of the charges valid over-ruled by FDA law and regulations.

The papers from the CDC claiming a relationship between opiate dose and death are not valid by both the FDA analysis and by JATH analysis. t

When physicians choose how to practice medicine, voluntary or non-binding) materials such as textbooks, lectures, advice of others, one’s own experience, non-codified Board of Medicine guidelines or suggestions, CDC guidelines, guidelines from associations serve as the resovior of information from which to built the individulized medical pracctice parameters, as long as those parameters do not lead to dangerous behavior. This is the role of regulatory agencies to make this determination. If the medical practice is shown to be dangerous by equivalent peers, then it must stop.

Laws and regulations are binding and must always be followed by physicians. Selling drugs is illegal (21 USC 841). Regulations promulgated by the DEA (Drug Enforcement Administration) are binding. Some Medical Board guidelines have been memorialized by statute, regulation or rule. A few states like Wisconsin and George have made medical board guidelines law. Most remain non-binding guidelines or suggestions.

Non-binding medical parameters are not appropriate for judging any medical practice unless the test for “dangerous” is met and the inquire is conducted by a panel of peers (using as a model the Court Martial). The peer panel doctors must have similar medical practices. Lieutenants do not try Colonels. Internists are not peers for neurosurgeons or psychiatrists. Common law is clear. Peer means peer, people belonging to the same rank, the same standing, practicing the same type of medicine.

For medical doctors, judgement criteria the “Standards of practice” widespread use by medical boards are if fact vague and capricious. and most fail the exact peer to peer standards. In fact the “standard of care” must be individualized on a case by case basis.

There are two basic standards for physician invesstigation: has a law has been broken, or is the physician is “dangerous” defined as a danger to the general public, the standard for most all medical boards.

The practice of medicine allows a wide range of parameters. Assuming innocence or non-dangerous behavior evaluated primarily by true peers, is the proper procedural rules when the outcome of adverse actions against the physican would be involuntary abandonment of patients.

Merely differing from other non-binding guidelines such as medical board “standards” or other guidelines and suggestions for medical practice. If this were not true, all suggestions, recommendations and guidelines, as well as textbooks, blogs, and medical board “guidelines” would have to be followed exactly leaving the physician rule bound and unable to make individual patient decisions tailored to the individual within context of their communities

Opiate dose restrictions created by states trying to override FDA authority under the Supremacy clause of the Constitution do so without legal standing. This is nullification.

Attempts to override the FDA’s law and regulations by other agencies, such as the CDC and the CMS, are violations of our system of laws and regulations, unless an FDA petition has been granted. No one can set dose limits except FDA. The EPA does not launch aircraft carriers and the defense department does not regulate the farming of cantaloupes.

The FDA, after reviewing the papers submitted by the PROP in 2012, cthere are just “as many problems with low doses as with high doses.” More information that the concept of “high dosage is bad” is not Until changed through legal means, the FDA remains the regulatory agency for opiate pain medicines. Until changed by FDA high doses are no more a problem than low doses.

The relationship between dose and overdose death should be more correctly listed as the relationship between opiate dose and death in general. When someone dies with an antidepressant on board, no one talks of “antidepressant overdose death.” Antidepressant blood levels provide proof.

To prove the death was directly related to the opiate medication, a standardized autopsy blood test for opiates must show toxic levels enough to cause death. The problem is, as far as we have found there is no reliable blood test. This surprising fact is due to the wide variation in blood levels and amount of opiates taken in general, and, most importantly, the individual differences in processing the opiate metabolites. This is part of the reasoning FDA does not put a maximum dose for opioid pain medicines — the wide variability discussed above.

The forensic diagnosis of opiate overdose death must be made by inference, a risky procedure fraught with bias and invalid determinants. Doing studies based on death certificates is considered so inaccurate that any study using death certificate coding is, in fact, invalid. All the studied reporting increased death rate from opiates or opiates and benzodiazipines use death certificate data automatically tainting the results.

A complete autopsy ruling out other causes would have to be done. There are millions of people taking opiate pain medicine. It is highly probable that many will die for other reasons while having the opiate on board and the “innocent bystander”. The complete negative autopsy helps validate the diagnosis of opiate overdose death but are rarely performed.

In summary, it is our finding that “high-dose” opiate pain medicines is a term without substance. There is no correlation between the milligram dose swallowed and the milligram dose that does its work in the body. The FDA, the regulatory agency for “opioids,” said it best: “The threshold for an increased risk associated with these drugs (opioids) could actually be considerably lower or higher than a maximum daily dose of 100 mg MME. (This was carried over to the CDC as 90 mg — the same thing.)

Using MME thresholds is now repudiated. AMA resolution 235, November 12, 2018 says “no entity should use MME thresholds as anything more than guidance, and physicians should not be subject to professional discipline, loss of board certification, loss of clinical privileges, criminal prosecution, civil liability, or other penalties or practice limitations solely for prescribing above the MME thresholds found in the CDC (guidelines).

The AMA has also said “some patients can benefit from taking opioids at greater dosages than recommended by the CDC” from AMA Statements, April 24, 2019

AMA further states: “the guidelines (CDC) have been misapplied so widely that it will be a challenge to undo the damage. AMA Statements, April 24, 2019

CDC says in issues that could put patients at risk: dosage recommendations that “result in hard limits (any MME cutoff) or (for) ‘cutting off’ opioids” . Not only are MME cutoffs not valid they can be dangerous for patient care. CDC Newsroom April 24, 2019.

Corresponding Author: Thomas Kline MD, thomasklinemd@gmail.com

42 years varied primary care • former Chief, Hospital in Home Service @harvardmed • formerly: @UofMaryland, @StanfordDeptMed, @uoregon • thomasklinemd.com