From: Todd Taylor [tbt@compuserve.com]
Sent: Friday, August 17, 2001 9:08 PM
To: Topper, Kimberly L
Subject: Comments for September 13-14 Meeting

TO: FDA Anesthetic and Life Support Drugs Advisory Committee

FROM: 
Todd B. Taylor, MD, FACEP
Emergency Physician
Good Samaritan & Phoenix Children's Hospitals, Phoenix, Arizona 
Home Office:
1323 East El Parqué Drive
Tempe, Arizona 85282-2649
Phone:  480-731-4665
Fax:    480-731-4727
E-Mail: tbt@compuserve.com

RE: Comments for September 13-14 Meeting: Relabeling of OxyContin and
"Black Box Warning" - Specifically "OxyContin Tablets are NOT intended for
use as a prn analgesic" and "analgesic is needed for an extended period of
time."

NOTE: I have placed my "conclusions" and "recommendations" at the beginning
of this document to help focus attention on my comments.

CONCLUSIONS

The recent relabeling of OxyContin (i.e. "OxyContin Tablets are NOT
intended for use as a prn analgesic" and "analgesic is needed for an
extended period of time") is inappropriate considering the huge benefit
such a medication has for the treatment of acute pain. There is no evidence
that this relabeling will prohibit the ongoing illicit abuse of this or any
other prescription narcotic mediations in America. Ill-advised warnings
will significantly reduce effective pain management and perhaps even worsen
the abuse by making it an even more "elite" drug. In addition, Purdue
Pharma's recently announced plans to mix microencapsulated naltrexone into
OxyContin tablets should eventually resolve most of the concerns regarding
hard-core abuse of this drug. 

From a pharmacological perspective, extended release narcotic pain
medications perhaps have dual roles. In chronic pain management a step-wise
and escalating dosing regimen is both appropriate and expected due to
tolerance. For this group, tablets with large doses (40mg or more) are
necessary and perhaps these doses should be limited to such patients, as
the new "Black Box Warning" seems to do. For acute pain management these
medications are equally appropriate but will typically be used in opiate
naive patients. Therefore, smaller doses per tablet would be more
appropriate and these doses should carry different labeling instructions.

RECOMMENDATIONS

In light of the above conclusions, I suggest that the FDA Anesthetic and
Life Support Drugs Advisory Committee consider recommending that the new
"Black Box Warning" apply only to OxyContin tablet doses of 40mg and higher
as theses doses would typically be intended for use in patients with
chronic pain syndromes and expected to develop tolerance over time. In
addition, it is these larger doses that have the most potential for
diversion and abuse.

I would further suggest that the Committee recommend to the manufacturer
Purdue Pharma that they develop a new package insert, with or without a
"Black Box Warning", with instructions for the use of 10mg and 20mg tablets
of OxyContin in acute pain management. This is clearly an appropriate, but
distinctly different indication than that for chronic pain. Purdue Pharma
may wish to repackage and/or rename the medication for this indication, but
that should be left up to its market research and business model.

COMMENTS

I have been a practicing emergency physician for 15 years and a leader in
the physician community. In my 15 years of practice I have seen several
medications come and go, but relatively few that altered my emergency
medicine practice or were significant improvements over prior available
therapies. For example, in the relatively few patents I see with an acute
MI certainly thrombolytics, despite intrinsic adverse effects, has made a
huge difference. But for the nearly 70% of patients that present with some
type of pain associated with a variety of disease processes, thrombolytics
pale in comparison to the benefits and minimal risks I have seen with the
use of extended release pain medications such as OxyContin.

I am often asked, "Why would you prescribe a 'cancer' pain medication to ER
patients." Such questions illustrate a fundamental lack of knowledge and
perhaps even a bias among physicians with regard to appropriate pain
management in the acute setting. My standard answer is, "well, how long do
YOU sleep at night?" Fact is, most patients treated with "traditional"
immediate release narcotic formulations sleep poorly, for short periods,
and are constantly cycling between pain and relief. Characterizing these
medications as only for "cancer-type" pain, in my opinion, has done a great
disservice to the American public and perpetuated a longstanding tradition
of under treating pain that the efforts of JCAHO and various pain
management organizations are actively trying to correct. On the one hand
doctors are being sued for "pain and suffering" for not giving appropriate
pain relief and now the FDA is scaring physicians by raising what, in my
opinion, are unsubstantiated concerns about extended release pain
medications. I would implore this panel to resist bowing to media attention
and use sound medical judgment as it deliberates the appropriate uses of
this and other similar medications.

As an emergency physician I rarely treat chronic pain, but the majority of
my patients present with some type of pain. Some of these patients have
failed outpatient management with what amounts to paltry doses of immediate
release pain medications prescribed by other physicians. Before medications
such as OxyContin became available I had few alternatives because of the
ceiling effect acetaminophen created in most other pain medication
formulations. Now the recent FDA focus on OxyContin that lead to the new
"Black Box Warning" has severely limited the ability of physicians such as
myself to appropriately treat patients with acute pain by prohibiting "prn"
dosing and by limiting OxyContin to when "analgesic is needed for an
extended period of time". I believe this change in labeling results from a
lack of appreciation by the FDA of just how poorly current "immediate
release, short acting" analgesics are for the treatment of acute pain and a
decision by the manufacturer, Purdue Pharma to abandon its promotion of
this drug for acute pain for "political and liability" reasons. And for
this, patients must now suffer unnecessarily.

The stated reasons for this change in labeling has apparently been because
of what has been hyped by the media as an epidemic in abuse of OxyContin.
While there have been examples of regional abuses, this is by no means an
epidemic and pales in comparison the abuse of shorter acting pain
medications such as the immediate release formulations of hydrocodone and
oxycodone with acetaminophen. Furthermore, there has also been considerable
media attention on deaths resulting from the "abuse of OxyContin" from
those who have taken large doses &/or crushed it in order to inject or sort
the drug. Theses 200 or so deaths, have almost all been associated with
co-toxicity with alcohol and other drugs and pale in comparison to the
15,000 or more death attributed to acetaminophen and other over-the-counter
medications each year.

The point that I am making is that the OxyContin formulation, when used
appropriately, is safer than many over-the-counter medications. The sheer
numbers of diverted prescriptions and abuse of immediate release
formulations of hydrocodone and oxycodone with acetaminophen vastly
outweigh those for OxyContin. Therefore the current efforts to relabel
OxyContin are limited to a bias ingrained in many members of the medical
community that the prescribed use of "narcotics" leads to drug
abuse/addiction. There is much evidence to the contrary and, in fact,
inappropriately treating pain can lead to "pseudoaddiction".

I also believe there are ethical issue to be considered if we are to limit
extended release pain medications to only those with chronic pain. While
acute pain may have a shorter anticipated duration, the pain itself may be
no less excruciating and rarely does acute pain last less than 8-12 hours.
How can we say to the 2 million or so chronic pain suffers, "yes YOU
deserve to have good pain control", but to the 80 million or more acute
pain suffers each year, "NO, you must tuff it out!" The pharmacology of
medications such as OxyContin clearly shows that its onset is 30-40 minutes
vs. 20-30 minutes for immediate release. This is clearly acceptable for
acute pain management and especially considering the extended pain relief
it offers. In my opinion the prohibition of "prn" dosing has absolutely no
scientific basis, the evidence is to the contrary, and it is unethical to
withhold such a useful medication for the treatment of acute pain. 

The "analgesic is needed for an extended period of time" warning is less
problematic although the implication perhaps is that OxyContin should only
be used for "chronic" pain. However, since one can easily justify
prescribing medication for the anticipated duration of symptoms and with
only rare exception does acute pain last less than 12 hours, I believe one
can justify the use of OxyContin in nearly all types of acute pain despite
this warning. Nevertheless, such a warning is more appropriate for the
larger doses of OxyContin that are truly intended to teat the chronic pain
patient that is expected to develop tolerance over time. Also, such a
warning may create unintended liability for physicians who prescribe
OxyContin for symptoms anticipated to last for only a few days.

Thank you for your consideration of my comments. Please feel free to
contact me should you have any questions or wish additional information. I
do not plan to attend the meeting, but would be available to do so if
requested by the committee.