Manufacturer Pushes New Narcotic for Even Mild, Transitory Pain. FDA Helps.

Oxymorphone is a highly addictive, semi-synthetic narcotic, which was first approved by the FDA in 1959 in both oral and injectable forms.  It is an active metabolite of oxycodone.  It is currently available as a 5 mg. suppository and an injectible (Numorphan) from Endo Pharmaceuticals.  Endo falsely claims that "Numorphan is a potent opioid analgesic" in the Physicians Desk Reference (2003).  It is highly addictive, but it has never been compared to the more potent non-narcotic pain relievers.

"New" immediate and long-acting forms are now being readied for sale by the same company which has recently completed phase III studies to obtain FDA approval and expects final FDA approval in early 2006.  Oxymorphone-ER is twice as potent as the infamous Oxycontin (oxycodone-ER) and much more potent than morphine or heroin (8.7 times as potent of morphine. J Clin Pharmacol 1977 Apr;17(4):186-98).  Of course, the FDA will rubber stamp any narcotic so long as it can be shown to relieve pain better than a sugar pill for any period of time, no matter how brief, and for any pain, no matter how minor.  

The FDA has recently sanctioned extremely bogus "research" to obtain approval.  Patients already habituated to narcotics were put on Endo's oxymorphone or placebo.  The one's switched to placebo reported more pain.  No where is there any reporting on how successful the blinding of this study was.  It is virtually certain that 100% of these patients knew immediately that they had been yanked off of their narcotics and were unhappy being given no pain reliever at all!  The manufacturer trumpeted the results in an Oct. 3rd press release.  In its most recent study, just published in December, 2005, Endo is promoting oxymorphone even for mild transitory pain (see below).  

Our government even helps recruit patients for the narcotic industry research through its website! (http://www.clinicaltrials.gov/ct/action/GetStudy )

Endo lists 12 of its 15 official FDA licensing phase II/III trials for oxymorphone IR and ER on its website.  In four, oxymorphone is compared to placebo and in the other eight, it is compared to another narcotic (morphine 2, oxycodone 6).  Not once is it compared to a non-narcotic pain reliever.  Three of the studies are for low back pain, two for osteoarthritis, four for post-surgical pain, and three with cancer patients.

Endo (Chadds Ford, PA. Tel: (610) 558-9800) specializes in narcotics and currently sells Percocet (oxycodone/acetaminophen), Percodan (oxycodone/aspirin), Zydone (hydrocodone/acetaminophen), and DepoDur (morphine extended-release liposome injection).  In addition to oxymorphone IR and ER, Endo is also developing a sufentanil patch and a sufentanil subcutaneous implant (Chronogesic).  It is in the phase II development of Rapinyl, a fast dissolving sufentanil tablet for so-called "break-through cancer pain," something that is very common in patients treated with narcotics, since narcotics don't work very well.  Sufentanil is another super-potent narcotic.  The market for strong narcotics is a $4.2 billion per year business and growing at 9% per year.  Narcotics are increasingly being given to all sorts of chronic pain patients.  Endo's partner, Durect, is targeting the "one in eight Americans" whom it claims suffer from chronic pain.  That's 34 million Americans whom Durect calls it's "Market Opportunity" for its extremely potent and addictive sufentanil narcotics http://www.durect.com/wt/durect/page_name/chronogesic 

Selling narcotics has been very good business for Endo.  The value of its stock (ENDP) has soared 300% since January, 2003

Most narcotic research is done by certain private clinics which seem to specialize in narcotic studies for drug manufacturers.  It makes you wonder how many of these patients were just recently yanked off an earlier narcotic for a couple weeks to have them ready for a new narcotic.  Some studies hint that up to half of their patients had been using some other narcotic prior to the study.

This is all so bogus that it is difficult for me to remain calm as I gather these nauseating "studies."  It's really sad to see Johns Hopkins involved in this.  In study after study, these friends of narcotic manufacturers are careful not to include non-narcotic pain relievers.  They also never report on how successful their blinding procedures were.  It's easy to do.  Just ask the patients to guess whether they were getting the narcotic or the placebo and calculate how good they were at guessing.  If patients know they received the placebo, it could seriously bias the results.

The only studies I could find comparing oxymorphone to a non-narcotic were two Canadian studies with post-surgical pain in dogs.  In both studies, the non-narcotic was clearly better than oxymorphone at pain relief.  Apparently, dogs are more important than humans to the FDA and America's "Independent" Review Boards (IRBs) when helping maximize the profits of investors is at issue.

Why aren't the IRBs requiring non-narcotic comparators?  Why does the FDA let narcotic manufacturers get away with placebo comparisons?  In view of the highly addictive nature and rampant black market consequences, shouldn't highly addictive narcotics be required to show that they are better than non-narcotic pain relievers, not just better than sugar pills?  Don't the consumers have a right to know?  Why isn't the DEA prosecuting Endo and its physicians for prescribing narcotics to individuals with brief, mild pain?  Isn't that a violation?  Everything in Washington is so corrupt these days with the Bush White House bending over backward to help narcotic manufacturers and narcotic salesmen (Endo says it has a sales force of 370 people. According to its Yahoo profile, it has 549 total employees! Assuming the sales force are all employees, that's 67% in sales).  

America is being destroyed from within.  Al-Qaeda doesn't need to worry.  Where I practice in the forests of rural northwest Pennsylvania, everything is going to hell in a handbasket with opiate addiction spreading like wild fire.  Some doctors hand it out like candy and high school and college students have no trouble buying it.  Every month I get patients who were hooked on narcotics by their doctors and students who have become heroin junkies, starting out with narcotic pills sold by patients on the black market.  Overdose deaths and drug related killings with even college students murdering each other are becoming commonplace, a dramatic change in just a couple years.  More and more people are contracting hepatitis B and C.  Young adults in the 20s and 30s, never before into illicit drugs, are being turned into junkies.  Already, since September 11, 2001, many more Americans have died as a result of overdoses of prescription narcotics, obtained both legally and illegally, than were killed by Al-Qaeda.

I'm also curious as to why the new patent law allows such slight modifications in a old drug's delivery system to grant a drug company a new patent good for 23 years of exclusivity and massive profits.  In the case of oxymorphone, it is a very old medication with no advantage over the many narcotics currently on the market (all of which are of very dubious value); the new delivery system is of absolutely no clinical benefit.  It is being done purely for financial greed.  Of course, most of those profits will come out of the pockets of consumers and tax payers in the form on higher prices in the store, higher insurance premiums, higher taxes, and lower international competitiveness due to our higher medical costs.

Endo Pharmaceuticals: 610-558-9800; David A.H. Lee, M.D., Ph.D. Chief Scientific Officer and Exec. V.P. who has exercised $13.85 million in Endo stock options in 2005 alone and is paid over $500,000 per year in addition to that.

Extremely Irresponsible Narcotic Researchers Promote Highly Addictive Narcotic for Even Mild, Brief Knee Pain: In a DB PC study of 122 out-patients after knee arthroscopy, these doctors proved that 5 mg of the highly addictive narcotic oxymorphone (immediate release) up to once per hour was somewhat better than placebo for mild to moderate acute post-surgical pain. 29% of the patients had only mild pain with the remainder only moderate pain. None had severe pain.  Of placebo patients, 52% did not ask for any pain medication vs. 83% did not ask of those on oxymorphone. Less than half the patients (47%) rated oxymorphone IR "very good" or "excellent" for pain relief (47%) versus placebo (25%). Gimbel JS, Walker D, Ma T, Ahdieh H. Efficacy and safety of oxymorphone immediate release for the treatment of mild to moderate pain after ambulatory orthopedic surgery: results of a randomized, double-blind, placebo-controlled trial. Arch Phys Med Rehab 2005 Dec;86(12):2284-9. 

    Ed: This is a highly unethical study in my opinion.  There is no non-narcotic comparison medication and the pain was at worst moderate, often only mild, and certain to be brief in duration.  To use a highly addictive medication in such a situation is simply immoral. Shame on the Archives of Physical Medicine and Rehabilitation for publishing this.  29% of the patients had only mild pain! Gimbel is a wealthy orthopedic physician who runs an independent center doing studies for drug manufacturers in Phoenix. Three of his four published studies on PubMed involve narcotics and all appear to have been funded by the manufacturers. To the best of my knowledge, at least two of the authors are Endo Pharmaceutical employees. How could an IRB approved this study?  What IRB did approve it?  Did the State of Arizona approve it?  Is it a violation of DEA licensure to prescribe highly addictive narcotics for mild pain?  Are there no DEA guidelines prohibiting the use of narcotics for mild and brief pain conditions?  Can narcotics now be prescribed like aspirin for a stubbed toe? How can the FDA let Endo pharmaceuticals get away with this?  Doctors and Lawyers for a Drug Free Youth has filed complaints with the FDA and DEA over this study and we are investigating the IRB and asking that its license to be an IRB be revoked.  We are asking for an investigation of Dr. Gimbel privilege of prescribing controlled substances.  Is there no responsibility anywhere for this corporate greed?  We are also requesting investigations of the medical licenses of Dr. Lee and the medical employees of Endo who designed and helped carry out this study.

Johns Hopkins Physician Unethically Helps Manufacturer Promote Highly Addictive Narcotic for Every Day Arthritis Pain: In a short, 4-week study of 370 adults with moderate osteoarthritis pain, a John Hopkins physician compared oxymorphone ER 20 mg, oxymorphone ER 40 mg, and oxycodone controlled release 20 mg, to a placebo every 12 hours. At three weeks, the oxymorphone ER 40 mg did only somewhat better than placebo (P = 0.015). The oxymorphone ER 20 mg at week 4 barely made a significant different compared to placebo (P = 0.050). The doctors state that the pain intensity decreased by only 30-40%. Side-effects were common: mild to moderate nausea, constipation, and somnolence. Oxymorphone Extended-Release Tablets Relieve Moderate to Severe Pain and Improve Physical Function in Osteoarthritis: Results of a Randomized, Double-Blind, Placebo- and Active-Controlled Phase III Trial. Matsumoto AK, et al. Johns Hopkins. Pain Med 2005 Sep-Oct;6(5):357-66. Ed: These coward physicians refused to compare this highly addictive narcotic to glucosamine and chondroitin or to an NSAID, both of which would probably have done as well or better.  What's more, the glucosamine and chondroitin would have actually helped the healing process and prevented any further deterioration.  Comparing highly addictive narcotics to sugar pills in very brief studies for common, chronic pain like arthritis is wrong.  These researchers should be investigated. Two of the three authors are Endo employees. I guess they don't trust Matsumoto to say the right thing. I am filed a letter to the Johns Hopkins ethics board.

Highly Addictive Narcotic Claimed Effective for Moderate Arthritis Pain in Bogus "Research:" In a 52-week "open trial" of 153 osteoarthritis patients with primarily moderate pain, only 40% of the patients completed the follow-up.  There was no blinding, no controls, no randomization, no active comparator, not even a placebo.  Yet, the physicians involved claimed their report proved the effectiveness of this highly addictive narcotic in treating chronic arthritis. Most withdrawals were caused by drug side-effects, a very high rate of drop-outs. Safety, tolerability, and effectiveness of oxymorphone extended release for moderate to severe osteoarthritis pain: a one-year study. McIlwain H, et al. Tampa Medical Group Research, Tampa, FL. . Am J Ther 2005 Mar-Apr;12(2):106-12. Ed: These doctors are advocating turning a large percentage of older Americans into long-term narcotic addicts.  This is wrong! Open trials are normally worthless.  This is even more true for highly addictive narcotics.  How many stayed in the study because they were too addicted to drop out?  How many said it helped so as not to lose their connection?  Where's the glucosamine and chondroitin, something that really works. An Endo employee with the other author of this paper.

Very Bogus Study Promotes Highly Addictive Narcotics for Chronic Lower Back Pain: In a bizarre 18-day supposedly double-blind PC study of 213 adults with chronic lower back pain, all patients received either oxymorphone ER (10 to 110 mg) or oxycodone CR (Oxycontin)(20 to 220 mg) every 12 hours during a 7- to 14-day dose-titration phase. Patients achieving effective analgesia at a stable opioid dose entered an 18-day double-blind treatment phase and either continued opioid therapy or received placebo. With stable dosing throughout the treatment phase, oxymorphone ER (79 mg/day) and oxycodone CR (155 mg/day) were supposedly superior to placebo for change from baseline in pain intensity as measured on a visual analog scale (P = .0001). These physicians claim that their study shows "Oxymorphone ER and oxycodone CR (a)re generally safe and effective for controlling low back pain." Efficacy and safety of oxymorphone extended release in chronic low back pain: results of a randomized, double-blind, placebo- and active-controlled phase III study. Hale ME, Dvergsten C, Gimbel. Gold Coast Research, Weston, FL. . J Pain 2005 Jan;6(1):21-8. Ed: This study conveniently eliminated right from the start anyone who didn't feel better on narcotics or who had serious side-effects.  Then, one third of the patients, after 14 days on powerful narcotics were suddenly put on look-alike sugar pills.  How many of these patients could tell that they weren't getting the real stuff?  The doctors don't tell us.  How many experienced narcotic withdrawal discomfort?  This issue isn't mentioned.  This is bogus.  There is no double-blind.  I am sure that 100% of placebo patients knew that they had been switched to placebo.  How do you think they felt without even be allowed an aspirin for pain relief?  Where is the vitamin D and vitamin K?  Where are the bisphosphonates?  Where is the glucosamine and condroitin?  An 18-day "study" for what is likely to be a lifelong problem.  This is wrong!  The "Arizona Research Center" was also involved in this study.  In narcotic studies, it always seem to be the usual line-up of suspects.  The authors of this paper have worked very closely with Endo Pharmaceuticals. Dvergsten is with INC Research, Charlottesville, VA.

University of Kentucky Claims to Prove Effectiveness of Oxymorphone-ER in Bogus Study: The University of Kentucky physicians admit that inadequate analgesia frequently result in the rotation of patients with cancer pain from opioid to opioid. In a bogus "study," they claim to prove "the analgesic effectiveness and safety" of  oxymorphone-ER by comparing it to morphine-CR and oxycodone-CR. Of 86 cancer pain patients with mostly moderate pain and already on narcotics, in only 63 were they about to arrive at a stabilized dose of morphine-CR and oxycodone-CR within 10 days. These patients were then switched to oxymorphone ER for 7 more days. There were no significant differences in daily pain intensity scores between oxymorphone ER and the other narcotics. Oxymorphone patients received an extra 13% of their total dose in PRN narcotic medications.  Effectiveness and safety of oral extended-release oxymorphone for the treatment of cancer pain: a pilot study. Sloan P et al. University of Kentucky Medical Center. . Support Care Center 2005 Jan;13(1):57-65.  Ed: This is another sad testament to the dishonest deceptions of the narcotic pain treatment industry.  All these researchers did is to show that oxymorphone is the same as morphine and oxycodone.  None of them have ever been compared to non-narcotic treatments for cancer pain.  The large number of extra PRN doses used shows that patients were still not doing well.  There is absolutely no evidence presented that shows that oxymorphone is any better than non-narcotic alternatives in the treatment of moderate or severe cancer pain.  A letter has been filed with the University of Kentucky Medical Center ethics board

Another Bogus Study Proving Only that a Highly Addictive Narcotic is Somewhat Better than a Placebo: In a supposedly double-blind, placebo-controlled study of 300 patients with mostly moderate postsurgical pain, oxymorphone IR 10, 20, or 30 mg was only somewhat better than placebo for 8 hour pain relief (P < 0.05). Discontinuations for lack of efficacy totaled only 42% among placebo-treated patients vs. 27% among those treated with oxymorphone IR, a small 15% difference. The efficacy and safety of oral immediate-release oxymorphone for postsurgical pain. Gimbel J, et al. Arizona Research Center, Phoenix, AZ. . Anesth Analg 2004 Nov;99(5):1472-7. Ed: This study made no effort to find out if patients figured out that they had been given sugar pills for their pain.  It is surprising how well placebo patients did.  I bet that a good non-narcotic pain reliever would have done just as well as the highly addictive narcotic and that the large majority of surgical patients, if fully informed that there is no difference in pain relief effective and if given a choice, would prefer to avoid narcotics entirely. An Endo employee was involved in this study.

Narcotics Pushed for Brief Moderate Knee Surgery Pain with Only Placebo Comparator: In a study of 126 patients with mostly moderate pain following knee arthroplasty who were only on patient-controlled narcotics, they were switched to receive oxymorphone-ER 20 mg. or placebo every 12 hours for 1 day. Patient controlled oxymorphone was used as an extra analgesic. Oxymorphone ER did better for total pain relief over 0 to 12 hours (19 vs. 14; p = 0.006), as well as for 24-hour assessments. Efficacy of oxymorphone extended release in postsurgical pain: a randomized clinical trial in knee arthroplasty. Ahdieh H, Ma T, Babul N, Lee D. David Lee is the executive vice-president and Chief Scientific Officer of Endo. This was an Endo study. J Clin Pharma 2004 Jul;44(7):767-76. Ed: This is another bogus study by the company itself encouraging a highly addictive narcotic for brief post-surgical pain with absolutely no evidence that a narcotic is of any advantage over many less expensive and non-addictive non-narcotics.  In my opion, in narcotic research the use of only placebo comparators is unethical.

No Difference Between Oxymorphone Extended Release and Oxycontin: In a DB crossover study of 47 patients with moderate to severe cancer pain, oxymorphone extended release (ER) was compared to oxycodone controlled release (CR).  Patients were first titrated for 3-10 days with open-label oxymorphone or oxycodone to achieve a stable dose that provided adequate analgesia with tolerable adverse events and no requirement for more than 2 doses of rescue medication per day. The subsequent double-blind treatment phase was a 7- to 10-day period of oxycodone CR or oxymorphone ER treatment followed by crossing over to the alternate medication for another 7-10 days. During the treatment phase, up to 2 doses per day of morphine sulfate 15-mg tablets were allowed as rescue. The average daily dosage of oxycodone CR (92 mg) was twice that of oxymorphone ER (46 mg). Rescue medication use was approximately 1 tablet of morphine sulfate 15 mg/day. No significant differences in opioid adverse events were observed. Establishing the dosage equivalency of oxymorphone extended release and oxycodone controlled release in patients with cancer pain: a randomized controlled study. Gabrail NY, Dvergsten C, Ahdieh H. . Curr Med Res Opin. 2004 Jun;20(6):911-8.  Ed: This is an unethical study cranked out for a narcotics manufacturer to help them push a dangerous and useless, highly addictive drug.  While the physicians put a positive spin on the study, it's pretty abysmal if a cancer patient is helped so little that he or she has to use a second narcotic an average of once every day.  Narcotics are grossly inferior for cancer pain and these patients were being irresponsibly and recklessly deprived of adequate pain relief, i.e, more effective, non-narcotic pain relief.

Irresponsible Endo Pharmaceuticals Proves Oxymorphone Better than Placebo in Knee Surgery: In a DB study of 126 patients suffering from moderate or severe pain following knee arthroplasty, they received 20 mg of an extended-release (ER) oxymorphone formulation (n = 65) or placebo (n = 61) q12h for 1 day. Oxymorphone PCA was used as rescue analgesic. Oxymorphone ER provided significant improvements over placebo for most standard single-dose analgesic parameters, including mean total pain relief over 0 to 12 hours (19.30 vs. 13.72; p = 0.0056), as well as for all multiple-dose (24-h) efficacy assessments. Oxymorphone-treated patients used significantly less rescue PCA than those who received placebo (p < 0.02). Adverse events such as nausea and constipation were typical of opioids, and laboratory and physical findings were similar between groups. These highly irresponsible physicians state, "Comparisons with other oral opioids are warranted, especially in the setting of outpatient and day surgery." Efficacy of oxymorphone extended release in postsurgical pain: a randomized clinical trial in knee arthroplasty. Ahdieh H, Ma T, Babul N, Lee D. Endo Pharmaceuticals Inc., Chadds Ford, PA 19317, USA. J Clin Pharmacol. 2004 Jul;44(7):767-76. Ed: It's a huge, corrupt game that narcotic manufacturers play with the FDA, showing that narcotics are better than placebos, and as good as narcotics.  They carefully avoid any comparison against non-narcotic pain relievers.  The FDA does not require that only narcotics be used as active comparators.  This is the choice of the manufacturer and their negligent researchers.

NSAID Ketoprofen (Orudis) Did Better than Oxymorphone for Post-Surgical Hind Limb Pain in Dogs: In a random-assignment study of 70 dogs undergoing orthopedic surgery on a hind limb, ketoprofen, oxymorphone hydrochloride, and butorphanol were compared for the control of postoperative pain. If the pain score was > or = 9, supplemental oxymorphone was administered IM. The ketoprofen alone and ketoprofen-oxymorphone groups did significantly better than the oxymorphone alone group. During the first hour after surgery, pain score was lower for oxymorphone alone and ketoprofen-oxymorphone groups than for ketoprofen or butorphanol alone groups. Significant differences were not detected among groups in regard to pain score 2 and 3 hours after surgery or in regard to arterial blood pressures at any time. From 4 to 12 hours after surgery, pain score was significantly lower for the ketoprofen alone group than for other groups. Except during the first hour after surgery, dogs given ketoprofen alone after elective orthopedic surgery had a greater level of, and longer-lasting, analgesia than did dogs given oxymorphone or butorphanol alone. Comparison of ketoprofen, oxymorphone hydrochloride, and butorphanol in the treatment of postoperative pain in dogs. Pibarot P, et al. University of Montreal, Canada. J Am Vet Med Assoc 1997 Aug 15;211(4):438-44. Ed: Ketoprofen (Orudis) is readily available in the U.S. for humans with a prescription for just $32 for 60 pills of 75 mg each, taken one three times a day. A long-acting form is available as Oruvail 200 mg once a day. The IM form is available as well. 

Ketorolac (Systemic) Much Better than Oxymorphone for Post-Surgical Laparotomy and Shoulder Arthrotomy Pain in Dogs: In a DB random-assignment study, ketorolac was compared with flunixin and butorphanol after laparotomy or shoulder arthrotomy in 64 dogs (butorphanol 0.4 mg/kg body weight (BW), flunixin 1.0 mg/kg BW, or ketorolac 0.5 mg/kg BW. The analgesic efficacy was (1 = inadequate, 4 = excellent) after laparotomy: ketorolac, 3.4; flunixin, 2.7; and butorphanol, 1.6. After shoulder arthrotomy, the average scores were ketorolac, 3.5; flunixin, 3.0; and butorphanol, 1.4 (5/11 dogs). As butorphanol was unable to control pain after shoulder arthrotomy, oxymorphone, 0.05 mg/kg BW, replaced butorphanol in a subsequent group of dogs and had a score of 2.0 (6/11 dogs). We concluded that ketorolac is a good analgesic for postoperative pain in dogs. A comparison of ketorolac with flunixin, butorphanol, and oxymorphone in controlling postoperative pain in dogs. Mathews KA, et al. Ontario Veterinary College, University of Guelph. Can Vet J 1996 Sep;37(9):557-67.