February 1, 2005
Documents Management Branch, Food and Drug Administration, Department of Health and Human Services, rm. 1-23, 12420 Parklawn Dr., Rockville, MD 20857
Citizen Petition
The undersigned submits this petition under Section 505b of the Federal Food, Drug and Cosmetic Act to request the Commissioner of Food and Drugs to temporarily revoke and/or permanently amend the FDA actions identified below.
FDA Actions Taken:
1) Title 21 CFR 314.105 Approval of (NDA) 020553 OxyContin 12/12/95
2) Title 21 CFR 314.105 Approval of (NDA)021044 Palladone 9/24/04
3) Title 21 CFR 314.70 Approval of Supplemental New Drug Applications providing for labeling changes of (NDA) 020553
11-20-03 (1-15-02, 7-18-01, 7-25-97, 6-21-96)
Actions Requested by Petitioner:
1) Temporary recall of approval of OxyContin (and generic equivalents) and removal from market until chemically reformulated by manufacturer(s) to drug of minimal abuse potential.
2) Temporary recall of approval of Palladone and removal from market until chemically reformulated by manufacturer to drug of minimal abuse potential.
3) Label changes limiting indications for OxyContin (and generic equivalents) to severe chronic pain from documented peripheral tissue disease processes.
4) Label changes limiting indications for Palladone to severe chronic pain from documented peripheral tissue disease processes.
I. Statement of Grounds – Overview
Numerous reports from across the country of death and addiction caused by OxyContin clearly document a national problem of escalating opioid abuse, diversion, and inappropriate physician prescribing.
Ø A recent University of Michigan study conducted for the National Institute on Drug Abuse found that despite a 17% overall decrease in illicit drug use among teens over the past four years, there has been a 49% increase in OxyContin abuse. 1.9 million individuals have used OxyContin for non-medical purposes at least once in their lifetime [Ref. #2] and non-medical use by people 12 or older rose from 399,000 in the year 2000 to 2.8 million in the year 2003. Between 1997 and 2002, there was a 400% increase in the medical use of oxycodone. During that same period of time, there was a 300% increase in abuse of oxycodone as recorded by DAWN data [Ref. #3].
Ø In the year 2000, the OxyContin problem had been located primarily in Maine, Pennsylvania, Kentucky,, Virginia, West Virginia, and Alabama. By 2001, it was a major and emerging problem in South Carolina, Florida, Tennessee, Montana, Louisiana, Texas, and Washington State [Ref.#1]. By 2004, the OxyContin abuse problem had affected multiple other states. Parts of Canada now have severe OxyContin problems (Nova Scotia and Ontario).
Ø An April 2002 report from the DEA implicated OxyContin as the direct cause or main contributing factor in 146 deaths and a likely contributor in an additional 318 deaths. The DEA based its findings on a survey of state medical examiners using autopsy data. A total of 949 reports were received, half of which involved OxyContin. More current figures seem to be unavailable but the death rate since 2002 continues to escalate.
Ø Non-medical use of prescription painkillers now comprises 30% of emergency room visits. The Department of Justice reports 20,000 prescription painkiller emergency room visits in 2002 alone.
Ø OxyContin death and addiction is not limited to those taking it for non-medical uses. Since Purdue Pharma’s 1997 launch of OxyContin into the moderate pain market and due to the company’s aggressive and untruthful marketing campaign, increasing numbers of patients legally prescribed OxyContin have suffered tragic devastation of their lives and/or death (reports and stories of such patients can be found at www.oxyconned.org ).
Ø On October 25, 2004 John Walters, White House anti-drug czar, announced in Missouri that the National Synthetic Drugs Action Plan is in response to the increased abuse of methamphetamines, Ecstasy and OxyContin.
Ø In an opinion issued on January 5, 2004 Judge Sidney Stein, federal judge in New York, ruled that the representations made by Purdue to the government concerning the effectiveness of OxyContin for chronic pain sufferers were fraudulent and misleading and that the patents issued to Purdue were therefore invalid. In particular, Judge Stein ruled that Purdue had misled the government by claiming that they had conducted clinical studies demonstrating OxyContin’s unique pain-relieving qualities when no such studies existed.
Ø In March, 2004 Lester Crawford, Acting Commissioner of the FDA, stated “ As beneficiaries of the world’s premiere health system, Americans should not have to endure preventable medical errors and adverse events related to medical products…Americans deserve better than settling for serious health consequences that can’t be spotted until many years after a product has been on the market.”
It is near the one-year anniversary of the General Accounting Office report on OxyContin abuse and the Florida Hearings before the U.S. House of Representatives Subcommittee on Criminal Justice, Drug Policy and Human Resources, at the latter of which, Robert Meyer, M.D. outlined a number of laudable FDA actions to prevent prescription drug abuse. As documented above, however, these efforts have fallen short, as the incidence of addiction and death from OxyContin has continued to escalate. Clear evidence of the severity of these adverse events has been known for more than five years, and the time is thus overdue to implement the more stringent measures requested in this petition. If it is appropriate to reevaluate the Cox-2 inhibitor pain medications, there is certainly a need for the FDA to reexamine regulation of the much more powerful and dangerous sustained-release opioids.
II. STATEMENT OF GROUNDS – SPECIFICS FOR REQUESTS #1
and #2
Ø In the current formulations of OxyContin and Palladone, full doses of oxycodone and hydromorphone can be easily converted from sustained to one-time immediate release. Ingestion of this immediate release form of the drug can be fatal or lead to opiate addiction. Large numbers of accidental overdoses of patients legally prescribed OxyContin have also been documented. (www.oxyconned.org).
Ø OxyContin (and soon Palladone) are easily available through Internet pharmacies. Legislation such as the Ryan Haight Act, co-sponsored by Senator Feinstein of California addresses this problem; however, the U.S. government is currently unable to regulate foreign online pharmacies. Unless OxyContin and Palladone are reformulated as abuse resistant, the current dangerously potent formulations will continue to be easily accessible.
Ø Randomized, double blind studies comparing OxyContin given every 12 hours with immediate-release oxycodone given four times daily demonstrated comparable efficacy and safety in chronic back pain [Ref. #4] and cancer pain [Ref. #5,6]. Compared with sustained release hydromorphone immediate release hydromorphone demonstrated no difference in efficacy and safety in cancer patients [Ref. #7,8]. Chou and colleagues in a recent review of the medical literature concluded that there is insufficient evidence to conclude that sustained release opioids have any better efficacy or safety than immediate release opioids [Ref.#9].
Ø Despite the wide publicity of the rapidly growing OxyContin problem since 2000, OxyContin sales have grown from about $1.2 billion in 2000 to about $1.9 billion in 2004 (IMS Health)----in spite of the lack of any scientific evidence that this is a better drug than what is available with other preparations.
Ø State Attorney General of Pennsylvania Jerry Pappert accurately stated that Purdue Pharma is not living up to its public commitment to reformulate OxyContin. He stated “We were told in April 2001 that they were aggressively researching adding anti-abuse ingredients to OxyContin, which would make the drug non-effective if a tablet was crushed and then snorted or taken intravenously by an abuser. The drug was expected to be ready in about three years. It is now (more than) three years later, and Purdue Pharma is currently stating in press reports that the drug development is 10 to 12 years away. They are working on a timetable that is financially best for them.” Pain Therapeutics Inc. (South San Francisco) has already received regulatory clearance to initiate clinical studies in the U.S. with Remoxy, a long-acting version of oral oxycodone that incorporates several abuse-deterrent properties. Additionally, a number of recent patent applications are pending, based on the strategy of combining an opioid with a chemical irritant that would be active when the drug is snorted, chewed or administered intravenously, but not when taken as prescribed, ie, swallowed whole [Attachment A]. Purdue Pharma’s claims that it will take 10-12 years to develop a less abuseable form of OxyContin are thus clearly innacurate.
Ø
By 2001, the increasingly
widespread pain and suffering associated with the diversion of OxyContin abuse
led some communities to formulate a national petition to recall Oxycontin
[Attachment
B]
www.recalloxycontinnow.org . The underlying thesis of the petition was that
the harm brought by the widespread availability of OxyContin on the market-place
was simply greater than the benefits of the drug; that there were equally
effective opioids available for treatment of severe pain, some of which posed
less abuse potential; and that nothing short of a recall could begin to address
the problem. The petition was introduced in California in late 2004. Currently
over 8,000 individuals have signed the petition online or in person, further
support for the position of this FDA Citizen Petition (signatures available upon
request).
At the February 2004 Florida hearing before the Subcommittee on Criminal Justice, Drug Policy and Human Resources, chairman Mark Souder emphasized the need for a regulatory plan that balances the competing concerns of those suffering from chronic pain and those whose lives have been devastated by OxyContin. The above documentation establishes both the unacceptable (and unnecessary) danger inherent in the current chemical formulation of OxyContin and the equivalent effectiveness of other preparations. This petition’s request for temporary recall of OxyContin (and generic equivalents) and Palladone until chemically reformulated by the manufacturer therefore would not compromise treatment of pain patients, would actually increase patient safety and is necessary if the single largest impetus for abuse of the drugs is to be eliminated.
III. STATEMENT OF GROUNDS – SPECIFICS FOR REQUEST #3
and #4
Ø Only two years after introducing OxyContin for the treatment of cancer-related and other severe pain, Purdue Pharma was allowed to extend its indications to moderate pain situations. At about the same time, the more potent 80 mg. And 160 mg. (1999) tablets were introduced. As a result of this expansion and Purdue Pharma’s aggressive marketing, two-thirds of all OxyContin prescriptions are now for non-severe, non-cancer pain, and OxyContin is the most frequently prescribed narcotic type pain medication. That the opportunities for, and actual incidence of, OxyContin diversion and abuse have grown exponentially during this time period is not a coincidence.
Ø In spite of concerns expressed by DEA officials (Wall Street Journal,
9/27/04), the FDA recently approved similar indications for the use of
Palladone, a drug acknowledged to be even more potent than
OxyContin.
Ø The Risk Management Plan (RMP) for Palladone (notably omitted for OxyContin), which mandates Purdue Pharma’s monitoring and reporting of adverse events related to the drug, really represents no improvement vis-à-vis a preventative effect on the OxyContin/Palladone problem. The RMP will only reinforce, in an after-the-fact manner, perspectives that are already well known, and depends for its impact on the fallacious premise that Palladone is appropriate for moderate pain. Having intervention strategies in place “in case these things (abuse, addiction, death) occur” is analogous to closing the barn door after the horse is out.
Ø “Educational” OxyContin label changes have been made with FDA approval on five occasions, the 7/18/01 change notably acknowledging the issue of misuse and abuse of the drug. Although well intentioned, none of these changes has reduced the scope of the problem (as previously documented in this petition it has worsened significantly). This is because they do not address its root cause –
failure to limit OxyContin use to severe, intractable pain from
documented peripheral tissue disease processes.
Ø When Purdue Pharma was allowed to broaden the indications for OxyContin, the way was paved for the legitimate (prescribing) use of the drug in a large population of patients based on symptomatology only. Unlike severe, cancer-related pain, “moderate” pain can be treated as a “disease unto itself” without essential attention being paid to the underlying cause (diagnosis). This is akin to using narcotic type pain medications – known to be effective – to treat chronic cough without establishing the source of the cough (pneumonia, tuberculosis, lung cancer etc.) [Attachments C & D].
Ø It is well recognized that pain may be centrally (brain) mediated only and originate from a number of psychophysiologic entities not involving true tissue damage. Appropriate management of this no less real type of pain involves the use of many modalities other than narcotic drugs, which can actually have adverse effects on brain chemistry.
Based on the above, there is no question that under current FDA prescribing regulations the harm produced by OxyContin considerably outweighs the benefits, and that continuing the current indication guidelines for OxyContin and Palladone will aggravate the societal devastation they have produced. These regulations also run contrary to both the stated mission of the FDA and several fundamental tenets of medical diagnosis and therapy. There is an urgent need for the FDA to rescind the current therapeutic parameters for OxyContin and Palladone, and to revert to “severe pain attributable to medically documented tissue disease processes” as the only indication for their use.
IV. Concluding Statements
This petition has provided evidence that there is a national problem of crisis proportions involving inappropriate prescribing, diversion and abuse of the drug OxyContin, and that a similar situation will occur with Palladone in proportion to its prescribing and availability. It has established that the FDA allowing liberalization of the original indications for use of the drug(s) and the continued existence of a hazardous chemical formulation have enhanced both the availability and inherent dangers of OxyContin. The petition has demonstrated that there is insufficient scientific evidence that sustained release opioids offer the improved efficacy over immediate release forms to justify the increased risk. It has shown that previous/current efforts by the FDA to address the problem have been unsuccessful and that the situation is worsening. It has pointed out that allowing use of OxyContin and Palladone for “moderate” pain indications violates several basic and important principles of medical diagnosis and therapy, as well as the FDA’s responsibility to its citizens. Finally, the petition demonstrates that the more restrictive regulations requested, while perhaps logistically and politically challenging, are warranted both from an historical and scientific standpoint and it calls upon the FDA to exercise bold and responsible action that will prevent many future tragedies.
Attachments
A. NATIONAL PETITION TO RECALL OXYCONTIN
Lee Coalition for Health
B. COMMENTARY ON THE PITFALLS OF OPIOIDS FOR
CHRONIC NON-MALIGNANT PAIN OF CENTRAL ORIGIN
Stephen G. Gelfand, M.D.
C. OXYCONTIN RISKS AND THE FDA
Stephen G. Gelfand, M.D.
References/Bibliography
1. Office of National Drug Control Policy, Pulse Check, April 2002
2. Woolf DJ, Hashmi, M. Use and abuse of opioid analgesics: Potential methods to
Prevent and deter non-medical consumption of prescription opioids.
Current Opinion in Investigational Drugs 2004 vol 5, No. 1, 61-66
3. Gilson A, Ryan K, Joranson D, Dahl J. A reassessment of trends in the medical
use and abuse of opioid analgesics and implications for diversion control: 1997-2002. Pain Symptom Management. 2004. vol.28 No. 2.176-188
4. Hale ME, Fleischmann R, Salzman R, Wild J, iwan T et al. Efficacy and safety of controlled-release and immediate-release oxycodone: randomized, double-blind evaluation in patients with chronic back pain. Clin j Pain 1999 Sep; 15 (30 179-83
5. Kaplan R, Parris WC, Citron ML, et al. Comparison of controlled-release and Immediate-release and oxycodone tablets in cancer pain. J Clin Oncol. 1998 Oct; (10): 3230-7
6. Stambaugh JE, Reder RF, Stambaugh MD et al. Double-blind, randomized comparison of the analgesic and pharmacokinetic profiles of controlled and immediate-release oral oxycodone in cancer pain patients. J. Clin Pharmacol. 2001 May;41(5): 500-6
7. Hays H, Hagan N, Thirlwell M, et al. Comparative clinical efficacy and safety of immediate release and controlled release hydromorphone for chronic severe cancer pain. Cancer. 1994 Sep 15;74(6); 1808-16
8. Bruera E, Sloan P, Mount B. A randomized, double-blind, double-dummy, over trial comparing the safety and efficacy of oral sustained-release hydromorphone with immediate-release hydromorphone in patients with cancer pain. Canadian Palliative Care Clinical Trials Group. J Clin Oncol 1996 May; 14(5): 1713-7
9. Chou R, Clark E, Helfand M. Comparative efficacy and safety of long-acting opioids for chronic non-cancer pain: a systematic review. J Pain Symptom Manage. 2003 Nov;26(50:1026-48
Certification Statement
The undersigned certifies, that, to the best knowledge and belief of the undersigned, this petition includes all information and views on which the petition relies, and that it includes representative data and information known to the petition which are unfavorable to the petition.
1/31/05
Signature Date
Barbara A. Van Rooyan
Name of Petitioner
Folsom CA 95630
Mailing Address
Telephone Number
1/31/05
Signature Date
Kirk W. Van Rooyan, M.D.
Folsom CA 95630
Mailing Address
Telephone Number
ATTACHMENT A
RECALL OXYCONTIN NOW
The Lee Coalition for Health in Lee County, Virginia has initiated the National Petition to recall OxyContin. While this is a complicated issue with many factors to consider, we feel that the pain and suffering brought to countless families and communities by the abuse of the drug far surpasses the benefits. It is clear by now that the best interests of the public health are served by the recall of OxyContin.
Why Recall OxyContin?
1. Fifteen months ago, we knew that some counties in Maine and our region in southwest Virginia were areas of heavy OxyContin abuse, dependence, and addiction. It's apparent over the last year that there has been extensive and rapid spread of this problem. There are major problems in Maine, Pennsylvania, New Jersey, Ohio, West Virginia, Maryland, Kentucky, Virginia, North Carolina, South Carolina, Florida, Louisiana, Mississippi, Wisconsin, Alaska, and Washington. It is being seen in a number of other areas. It is a national problem.
2. There are a number of important measures to take in trying to cope with this problem. Public education, prevention initiatives, more prudent physician prescribing, better tracking and detection systems for prescription fraud or diversion, more comprehensive law enforcement efforts, and greatly expanded treatment capacities -- are all critically important measures. However, all of these will move too slowly and will fall short in halting the rapid and devastating spread of the OxyContin abuse epidemic in the United States.
3. The pain and suffering brought to countless families and communities by the abuse of the drug greatly surpasses the benefits of the drug.
4. It is important to understand that there are very good alternatives to OxyContin for patients with severe pain. A recall of OxyContin would not mean that the medical community would be abandoning the treatment of severe pain. As physicians, this is one of our largest responsibilities -- the thoughtful and compassionate treatment of pain. TThere are several other good pain medications on the market that are as effective and as strong as OxyContin. These include transdermal fentanyl patches, sustained release morphine pills and methadone tablets. Patients with severe pain can be reassured that we do have equally effective medications and at least some of these have less abuse potential than OxyContin.
5. OxyContin can, should, and will be re-formulated to a preparation of much less abuse potential. It needs to be off the market until that is done.
Art Van Zee, MD and Vince Stravino, MD
Lee Coalition for Health
P.O. Box 578
Pennington Gap, VA 24277
Prior to going online July 20, 2001 - Over 6.950 signatures received
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To: international
National Petition to Recall OxyContin
Whereas, OxyContin abuse has reached epidemic proportions in many regions of the United States and has been destructive of countless futures, families, and communities; Whereas, public education; prevention initiatives; more prudent physician prescribing; improved treatment services; and more comprehensive law enforcement efforts---are all critically important, but much more is needed to halt the increasingly widespread abuse of Oxycontin; We, the undersigned, call upon the FDA and Purdue Pharma to recall OxyContin until it can be reformulated to a medication of minimal abuse potential.
Sincerely,
The National Petition to Recall OxyContin Petition to international was created by and written by Art Van Zee, MD. This petition is hosted here at www.PetitionOnline.com as a public service. There is no express or implied endorsement of this petition by Artifice, Inc. or our sponsors. The petition scripts are created by Mike Wheeler at Artifice, Inc. For Technical Support please use
700 Total online Signatures
1-16-05
6950 signatures prior to going online
450 additional (pen and paper)
signatures since petition introduced
in California October 2004
1-16-05
View Signatures : 700 650 600 550 500 450 400 350 300 250 200 150 100 50
The National Petition to Recall OxyContin Petition to international was created by and written by Art Van Zee,MD. The petition is hosted here at www.PetitionOnline.com as a public service. There is no express or implied endorsement of this petition by Artifice, Inc. or our sponsors. The petition scripts are created by Mike Wheeler at Artifice, Inc. For Technical Support please use our simple Petition Help form.
Epidemic of OxyContin Abuse
Dr. Art Van Zee
July 20, 2001
In my experience in primary care general internal medicine for the last 25 years in Lee County, there has always been a certain level of drug abuse -- both of illegal drugs and prescription drugs. However, there has never been anything like what we have witnessed in the last two years. There has been a virtual epidemic of Oxycontin abuse and subsequent opioid (narcotic) addiction. Oxycontin has been snorted or injected IV, males and females, from mid-teens to early forties. There have been numerous over-doses (some fatal), infections, increasing Hepatitis C, and occasional case of endocarditis related to this. Numerous young people have been losing their jobs, vehicles, houses, and children to this addiction. Many of these young people are very good kids, coming from good solid families, and who have had bright, promising futures until they did make the mistake of recreationally using and abusing prescription drugs. Oxycontin became rapidly addicting for them, and they have suffered severe consequences of their opioid addiction, devastating not only their own lives but the lives of their families and loved ones. There are very few families in our region who have not been directly or indirectly affected by this problem. The medical, personal, social, and societal toll has been, and continues to be, huge. The medical community has not had the capacity or resources to deal with the large scale opioid dependence that we have had. In-patient and out-patient facilities are limited. At our closest in- patient drug detoxification facility --"The Laurels" in Lebanon, Virginia, the percent of patients using opioids has increased from 18% to 44% in the last 4 years. Our closest methadone maintenance clinic in Knoxville is a two and a half hour drive, and many parents leave at 4A.M. to drive their children down to the clinic. The DRD Knoxville Medical Clinic can document what a tremendous increase in opioid addiction there has been in the region in the last few years. The Life Center of Galax opened an out- patient methadone maintenance clinic in March, 2000 -- anticipating about 15 patients at the end of the first year, based on the known prevalence of heroin in the region. They had 30 admissions within the first two weeks of opening, and within 6 months had 254 patients, 95% of them entering the program with Oxycontin addiction. Law enforcement has been over - whelmed by the associated problems, as drug related crime has sky-rocketed. The county sheriffs in the region document that 70 - 80% of the major crime over the last two years has been drug related, and most of that Oxycontin.
The county Social Services Departments have likewise been over-whelmed. The number of children needing to be placed in foster care has tripled over the last 4 years in Lee County, primarily related to Oxycontin abuse.
In the spring of 2000, the Oxycontin abuse epidemic appeared from the media to be primarily located in southwest Virginia and Maine. Numerous other states now have major problems with this including Pennsylvania, Ohio, West Virginia, Kentucky, Maryland, North Carolina, South Carolina, Florida, Alabama, Mississippi, Louisiana, and Alaska. Other states including New Jersey, Arizona, Wisconsin, Michigan, and Kansas are beginning to record significant problems. Clearly, this is a growing national problem.
Alternatives to OxyContin
There are several strong pain medications (opioids) which are just as effective as treating severe pain as in Oxycontin. There are no studies in the medical literature which demonstrate Oxycontin has clear cut superiority over immediate release oxycodone, controlled release morphine, transdermal fentanyl patches, or methadone when used in the treatment of severe pain. Some of these have less abuse potential, and some of these offer significant cost savings over Oxycontin. In reviewing oxycodone and Oxycontin in the September 17, 2001 issue, The Medical letter concluded:
"Oxycontin is a q12hour controlled-release formulation of oxycodone that can be used effectively in the treatment of pain due to cancer and, occasionally, other types of chronic pain. There is no evidence that oxycodone offers any advantage over appropriate doses of other opioids, and it appears to have the same potential for addiction as morphine."
Some of the studies are summarized briefly below--
Comparison: Immediate release oxycodone versus Oxycontin
Hale ME, et al Efficacy and Safety of Controlled-Release Versus Immediate-Release Oxycodone: Randomized, Double-Blind Evaluation in Patients with Chronic Back pain Clin J Pain 1999 Sep:15(3): 179-83 ** Conclusions: 47 Patients randomized "controlled-release oxycodone given every 12 hours was comparable with immediate-release oxycodone given four times daily in efficacy and safety...."
Kaplan R, et al Comparison of Controlled-Release and Immediate-Release Oxycodone Tablets in Cancer Pain J Clin Oncol 1998 Oct:16(10):320-7 ** Conclusions: 160 patients, double blind study "CR and IR oxycodone were equally effective in the management of cancer-related pain" -- "..the adverse event profiles of CR and IR oxycodone were similar. Overall, however, significantly fewer adverse events were reported for CR oxycodone compared with IR oxycodone..." (somewhat less nausea and vomiting with CR oxycodone)
Stambaugh JE, et al Double-Blind, Randomized Comparison of the Analgesic and Pharmacokinetic Profiles of Controlled and Immediate-Release Oral Oxycodone in Cancer Pain Patients J Clin Pharmacol 2001 May:41(5):500-6 ** Conclusions: 32 Patients "CR provides equivalent analgesia as IR oxycodone with the same patient acceptance profile" "..similar incidences and numbers of reports of individual adverse events considered related to the IR and CR drug"
Comparison: Controlled-release morphine versus controlled-release oxycodone (Oxycontin)
Heiskanen T and Kalso E. Controlled-release oxycodone and morphine in cancer related pain. Pain 1997 Oct:73(1):37-45 ** Conclusions: 45 Patients in a double-blind, randomized, cross-over "the two opioids provided comparable analgesia" "the total incidence of adverse experiences reported by the patients was similar, but significantly more vomiting occurred with morphine, whereas constipation was more common with oxycodone."
Mucci-LoRusso P, et al Controlled-release oxycodone compared with controlled-release morphine in the treatment of cancer pain: a randomized, double-blind, parallel-group study. European Journal of Pain (1998) 2:239-249 ** Conclusions: 100 patients-- "controlled-release oxycodone was effective as controlled-release morphine in relieving chronic cancer-related pain.." "the side-effect profiles of CR oxycodone and CR morphine were similar overall in this trial."
Bruera E, et al Randomized, Double-blind, cross-over trial comparing safety and efficacy of oral controlled-release oxycodone with controlled-release morphine in patients with cancer pain. J. Clin Oncol 1998 Oct:16(10):3222-9 ** Conclusions: 23 patients "There were no significant differences detected between the two treatments in ...adverse events, or clinical effectiveness..."
There are no studies that we are aware of comparing controlled-release oxycodone (Oxycontin) with transdermal fentanyl or oral methadone for treatment of severe chronic pain.
There are a few studies comparing transdermal fentanyl with oral morphine.
Transdermal fentanyl versus oral morphine
Payne RJ Quality of life and cancer pain: satisfaction and side effects with transdermal fentanyl versus oral morphine. Clin Oncol 1998 April 16(4):1588-93 Conclusions: 504 patients "these data suggest that patients are more satisfied with transdermal fentanyl compared with sustained-release morphine"
Ahmedzai S.J. Transdermal fentanyl versus sustained-release oral morphine in cancer pain: preference, efficacy, and quality of life. J. Pain Symptom Management 1997 May: 13(5):254-61 Conclusions: both were equally effective in terms of pain control: there was less constipation and sedation with fentanyl.
Art Van Zee, MD
Lee Coalition for Health
10/1/2001
What is the Lee Coalition for Health?
Lee Coalition is a non profit- coalition of professionals and other concerned citizens founded 10 years ago to promote health and wellness issues in Lee County, Virginia. Some of the Coalition projects have included:
· An annual free cancer screening for Lee County residents for the last 10 years.
· Tobacco education in the middle schools.
· Smoking cessation classes.
· Fire prevention activities.
· Healthy heart cook- books.
· A community smoking cessation contest.
· After prom party.
· Asthma camp.
Attachment B
COMMENTARY ON THE PITFALLS OF OPIOIDS
FOR CHRONIC NON-MALIGNANT PAIN OF CENTRAL ORIGIN
Stephen G. Gelfand, M.D.
There is a serious medical and social problem today under intense media, law enforcement, and regulatory scrutiny concerning the misuse and abuse of OxyContin for chronic non-malignant pain. This situation has made the drug difficult to obtain for many patients with malignant and other types of intractable chronic pain, and has recently influenced the FDA to issue a black box warning in order to lessen the chance of inappropriate prescribing of this Schedule II narcotic. In addition to recent D.E.A. autopsy findings of nearly 300 OxyContin overdose deaths nationally since January 2000, there is a large volume of patients with chronic non-malignant pain who have become dependent or addicted as a result of legitimate prescriptions written for OxyContin [as well as other opioids]. In a recent case, the D.E.A. suspended physician narcotic licenses and closed a South Carolina pain clinic for the excessive prescribing of OxyContin, although the physicians involved believed they were following current established standards [New York Times, Dec. 10, 2001].
How did this situation occur? In the first place, on closer inspection, certain statements in the narcotic guidelines established by the Federation of State of Medical Boards [1] have received insufficient or cursory attention. These include the recommendations pertaining to the importance of psychological and substance abuse evaluations, the necessity for other treatments depending upon the etiology of the pain and extent of psychosocial impairment, and the requirement for consultation with or referral to an expert for comorbid psychiatric disorders. These are common omissions, particularly in rural environments, where the OxyContin problem first originated, and in which psychosocial factors receive less attention, resulting in fewer numbers of and referrals to mental health providers. Even before OxyContin, however, another opioid, hydrocodone, was one of the most widely abused drugs, particularly in rural areas of the South[2].
Clearly, the large volume of prescriptions and chronic use of OxyContin have increased the supply, availability, and opportunities for every type of abuse, while also filtering into our schools. Contributing to this situation has been an attempt to expand the indications for opioid therapy to the entire spectrum of chronic pain, regardless of cause. As a result of an organized educational and marketing campaign by the manufacturer of OxyContin and a number of pain societies, the message has spread that there is too much undertreatment of pain in general, and that opioids are safe in most instances and should be prescribed more often for chronic pain of all types [3,4]. There would be general agreement with this appeal if restricted to patients with cancer or other forms of intractable peripheral pathology, but it is also intended and has been used for many patients with non-malignant, non-structural chronic pain.
Since chronic widespread pain and psychological distress in the general population are closely associated [5], the indications for opioids have thus been expanded to this large population of patients with chronic pain of central affective origin, including those within the wide spectrum of fibromyalgia, one of the most common rheumatic disorders. Thus, the indications for opioid therapy has been extended to this large, heterogeneous group closely associated with a wide range of psychological distress, including the affective spectrum disorders [6]. It is these vulnerable patients who are at risk for the dangers of opioid therapy, especially in rural regions where insufficient attention is given to pain-generating and amplifying psychosocial factors, in lieu of a more patient-popular drug-oriented approach.
The current “pain revolution” has also widened the use of opioid drugs for chronic pain by focusing on quantitative criteria such as degrees of pain [a largely subjective parameter], rather than on etiology. However, the degree of pain often correlates poorly with objective findings, and quantitative factors have different levels of significance for the types of chronic pain common to different specialties, i.e. oncology as opposed to rheumatology. This approach does not account for the essential distinctions in the biological and psychological origins of chronic pain subgroups, which are important to understand in making informed therapeutic decisions. Furthermore, the appeal to broaden the indications for opioids has also trivialized possible long-term adverse consequences, particularly of OxyContin [3,4]. Consequently, as cited above, a number of pain clinics have formed for the major reason of prescribing analgesics, especially opioids, while at the same time frequently downplaying or disregarding non-pharmacological approaches including psychological testing and management necessary for a large number of the chronic pain population . Thus, the combined effect of expanding the indications for opioid use, and insufficient attention to guideline recommendations, has facilitated the current environment of OxyContin abuse which has grown into a major medical, social, and law enforcement problem in many rural areas, as well as in an increasing number of metropolitan regions throughout the country. The extent of this situation, which often involves law-abiding citizens, was recently reported in special television broadcasts on both CBS News’48 HOURS entitled “Addicted”, anchored by Dan Rather, and MTV’s: “True Life: I’m Hooked on OxyContin”. Susan Zirinsky, executive producer of “Addicted” which aired on Dec.12, 2001, states that “the growing addiction to prescription painkillers is a story that is touching every age group, and its effects are often devastating”. In the last several years, OxyContin abuse and addiction have quickly spread and have reached epidemic proportions.
Pain is a complex sensation modulated by central brain pathways, including the nerve centers and networks responsible for emotions. The types of chronic pain for which opioids were originally intended are caused by pathological processes in tissues or organs from diseases such as cancer or intractable nerve or joint damage. In these conditions, the drugs combine with opioid receptors on nerve cell bodies in the brain and spinal cord which connect to and attenuate the electrical activity of these afferent nerve pathways stimulated by peripheral tissue lesions. However, in other common types of chronic pain, similar structural abnormalities in peripheral tissues are not present; instead pain is produced and intensified by central brain mechanisms, including emotions, which are stimulated by a spectrum of chronic psychological distress, and results in disordered central pain regulation and amplification [7]. This latter type of chronic pain includes the fibromyalgia syndrome, in which symptoms have neurophysiological correlates originating from persistent central nervous system activation from a large range and degree of stressful psychosocial life events [8]. The outcome is a persistent chronic stress response characterized by dysfunctional neuroendocrine reactivity to psychological, as well as to physical and physiological stressors [9,10,11]. Since opioids may have mood-elevating or altering effects, particularly in individuals with chronic pain and psychic distress [conscious or subconscious], these drugs may facilitate psychological dependence by their action on central affective nerve networks, as opposed to the peripheral afferent nerve pathways of tissue damage or destruction. In essence, it appears that opioids work on different nerve pathways in fibromyalgia than they do in cancer, intractable nerve damage, or end-stage arthritis. This central action may also occur in vulnerable patients with non-structural low back pain and tension headache.
The localization of opiates in the pleasure centers of the human brain and the recent demonstration of mu opoid receptors in the amygdala of nonhuman primates [12], a brain region essential for emotional content and behavior, is further evidence of the intimate relationship between emotional states and pain processing. In my view, the treatment of pain of central origin should focus on attenuating the causative and perpetuating psychobiological factors, rather than masking them with exogenous opioids. These drugs carry the risk of long-term dependency or addiction by their direct effects on the emotional component of pain while depleting the brain’s natural endogenous opioids.
Even in conditions of chronic pain associated with peripheral pathology such as the synovial inflammation or cartilage destruction of arthritis, central pain-modulating mechanisms may play an important role, a fact which has definite therapeutic implications. For instance, the recognition and management of underlying psychological disorders in patients with rheumatic diseases can significantly improve pain levels and function [13]. Self-management programs including education, exercise, and behavioral-cognitive therapies have likewise resulted in positive benefits beyond that of drug therapy alone [14,15]. Furthermore, dependence upon painkillers including opioids, may directly inhibit the learning of the construct of self-efficacy, which affirms the belief that people themselves, with their own resources, can significantly reduce pain and other symptoms [16]. Unfortunately for too many today, “taking a pill is easier than building the necessary will”, a socio-cultural reality contributing to our national problem of prescription drug abuse, including that of OxyContin.
Self-efficacy and dependence upon drugs for pain are opposite therapeutic objectives. Although certain medications such as low dose tricyclic antidepressants for improved sleep, and SSRIs for depression and /or persistent pain are beneficial in selected patients, conventional drug management by itself has not been shown to improve outcomes in fibromyalgia [17,18]. The same conclusions also apply to chronic low back pain not caused by specific structural lesions. Both conditions frequently have multiple psychosocial and cognitive variables unique to each individual which need to be recognized and treated as part of a multidisciplinary treatment program including self-management techniques. Disregarding these factors, which are essential in the origin and amplification of symptoms, predisposes to polypharmacy, drug dependence, and a dysfunctional state in which each symptom is medicalized.
One of the most common reasons for patient visits today is the large range and severity spectrum of multiple unexplained symptoms, including pain, which are associated with stressful life events, psychological distress, depression, and anxiety disorders [19]. Fibromyalgia syndrome should be viewed and managed in this broader context, rather than as a discrete disease requiring medications [including opioids] as principle therapy. Recognition that a number of these patients would rather have a “physical disease” than confront the effects of stressful past or present life circumstances may be helpful in their overall evaluation process. Furthermore, this comprehensive approach considers the chronic muscle pain of fibromyalgia syndrome to be just one of many symptoms that can be generated by chronic tension and stress originating from biopsychosocial factors, rather than as a distinct disease in the traditional biomedical sense [8].
The lessons of OxyContin could serve to strengthen the importance of good clinical judgement and the need to evaluate each patient in context. This includes determining whether chronic pain originates from peripheral or central mechanisms, and adhering to the narcotic guideline recommendations for adequate psychosocial evaluations prior to prescribing opioids. Pain should not be treated in isolation without understanding it’s roots, just as fever mandates a search for causes. Undertreatment should refer not only to drug therapy, but also to the absence of important non-drug interventions. The appropriate management of chronic pain is multimodal including non-pharmacological therapies, especially for pain of central origin. Diagnosis and care should be individualized and involve other disciplines as indicated, including clinical psychology, psychiatry, stress management, health education, and physical and/or occupational therapy.
As a result of the OxyContin problem, certain pain societies are now calling for a more balanced approach to the diagnosis and management of chronic pain [20]. Hopefully, the aftermath of OxyContin will show that a “one drug fits all” orientation to chronic pain is a risky practice with many pitfalls. In the public interest, more attention must be paid to proper patient selection rather than to marketing ploys intended to increase company drug sale figures.
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18. Lautenschlager J. Present state of medication therapy in fibromyalgia syndrome. Scand J Rheumatol Suppl 2000;113:32-6.
19. Katon W, Sullivan M, Walker E. Medical symptoms without identified pathology: relationship to psychiatric disorders, childhood and adult trauma, and personality traits. Ann Intern Med. Suppl 2001;134:917-25.
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Stephen G. Gelfand, M.D.
Intracoastal Arthritis & Rheumatology, PC
3516 Caduceus Drive
Myrtle Beach, SC
843-293-1022; fax: 843-293-0096
Attachment C
