Health Canada has announced that the label for Botox Cosmetic Products sold in that country will be updated to include new safety warnings. The warnings will now include the risk of the toxin spreading to other distant parts of the body. Possible symptoms of “distant toxin spread,” which can be fatal, include muscle weakness, swallowing difficulties, pneumonia, speech disorders and breathing problems, Health Canada said.
Botox and Botox Cosmetic, manufactured by Allergan Inc., is the only botulinum toxin products marketed in Canada. Botox is indicated for the treatment of muscle spasms in the neck, eye and foot, muscle pain, and excessive sweating. Botox Cosmetic is indicated for cosmetic purposes, to treat facial wrinkling.
In October, Health Canada said that five Canadians have died following Botox injections, prompting it to launch an investigation. At the time, Health Canada said it was also looking into eight reports of serious reactions following Botox treatment. The Botox reactions reported in Canada included throat swelling, respiratory arrest, difficulty swallowing and aspiration pneumonia, and infection that occurs when food or liquids are inhaled into the respiratory tract and lungs.
According to Health Canada, only one of the 13 reports it had received as of March 28 involved using Botox for wrinkles, and none was medically confirmed as “distant toxin spread.” However, “10 of the 13 cases were deemed to be serious owing to life-threatening reaction (one case), hospitalization (three cases), ongoing disability (one case) or fatal outcome (five cases),” the agency said in its most recent adverse reaction newsletter.
Two deaths occurred in children with cerebral palsy. As is the case in the U.S., Botox has not been approved for such use in Canada. The other deaths involved three women in their 60s, all of whom had underlying medical conditions such as Parkinson’s or cerebral palsy.
In addition to announcing the new labeling, Health Canada has advised Canadians using Botox and Botox Cosmetic products to seek immediate medical care if swallowing, speech or breathing disorders arise. Canadians with a history of underlying neurological disorders, swallowing difficulties and/or breathing problems should use these products with extreme caution. Botox and Botox Cosmetic products should only be used under specialist supervision in those patients and should only be used if the benefit of treatment is considered to outweigh the risk, Health Canada said.
Last February, the U.S. Food & Drug Administration (FDA) launched its own investigation of botulinum toxin injections, including Botox, Botox Cosmetic, and Mylobloc. In the U.S., Botox is approved for treatment of conditions such as blepharospasm (spasm of the eyelids), cervical dystonia (severe neck muscle spasms), and severe primary axillary hyperhydrosis (excess sweating). Botox Cosmetic, is approved for temporary improvement in the appearance of moderate to severe facial frown lines. Mylobloc is approved for the treatment of adults with cervical dystonia.
The FDA said at the time that it had received reports of adverse reactions in patients receiving the injections. The most serious cases had outcomes that included hospitalization and death, and occurred mostly in children treated for cerebral palsy-associated limb spasticity. Use of botulinum toxins for treatment of limb spasticity (severe arm and leg muscle spasms) in children or adults is not an approved use in the U.S. The FDA said that the adverse reactions may have been due to overdosing.
Last month, we reported that Australian health regulators revealed that a mother treated with another botulinum toxin Type A product gave birth to a baby with severe birth defects. The drug implicated in that incident is called Dysport, which while not yet approved in the U.S., contains the same active ingredient found in Botox and Botox Cosmetic.
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March 9th, 2009 at 1:18 pm
In 2003 I reviewed a study submitted by Alistair and Jean Carruthers
to the Journal Dermatologic Surgery which concluded the dilution of
Botox did not matter. A review of the paper uncovered serious problems with the manuscript, including graphs demonstrating a worsening of wrinkles after the Botox wore-off. Based on these problems and the small number of subjects in the study it was rejected for publication.
The author then resubmitted the study with different data. I alerted the editor of the Journal Dermatologic Surgery, William Colman to this highly suspect data change and was assured that this problem would be resolved.
Ultimately, this study appeared two years later (December 2007) in a special Allergan sponsored edition of Dermatology Surgery, with the modified data to support the author’s claims that dilution of the toxin did not matter. Here we have foreign doctors without a license to practice medicine in any State or green presenting altered data to the medical community on behalf of a pharmaceutical company within the America. While they may have recently been given a green card the for 10 years in the The literature was once widely considered to be the holy grail of medicine. The FDA had previously written on Botox and considered improper dilution to be the greatest problem with its use. For example large dilutions of Botox solution posed a serious danger to patients because it could spread to unintended areas and muscles of the body. I complained about the above article both to David Pyott at Allergan and Dermatologic Surgery. Shortly, thereafter I was fired from Allergan and let go by William Coleman as an editor of Derm Surgery. When attempting to warn the medical community of this issue my articles were rejected from Dermatologic Surgery and Journal of the American Academy of Dermatology.
Arnold Klein MD
Professor of Medicine and Dermatology
David Geffen School of Medicine at UCLA
Arnold Klein Chair in Dermatology-Founder
March 13th, 2009 at 3:22 pm
Physicians supported by America’s big pharmaceutical companies are the very same people who run medical societies, edit and advise trade publications, appear on the internet and television, and speak before the FDA. These physicians are responsible for the recent FDA approval of synthetic permanent injectable agents as well as other synthetic products that are placed under the skin. These products have gained approval despite a total lack of information and scientific data concerning their behavior once implanted. Some of these agents have had a disastrous history abroad, but the FDA aesthetic device panel showed disinterest in these studies. This was a bit confusing because the lead physicians appearing before the FDA and supporting many of these agents were foreign and not licensed in the U.S. The fact that they would practice medicine without a license in the United States seemed of no concern to the FDA. Furthermore, these physicians’ ownership of stock in these companies was frequently not disclosed to the FDA. Often times even the studies they performed were done outside the country, yet the FDA was most accepting of this data.
The following demonstrates the complicated ethical issues that arise when physicians and powerful pharmaceutical companies attempt to compromise and influence the medical literature, the holy grail of medicine: A few years ago, the lead consultant for the company Allergan, which manufactures Botox, attempted to publish a manuscript that supported the concept that dilution of the agent did not matter. It has long been known that large dilutions of the vial of toxin could result in the toxin migrating and reaching unintended muscles. Furthermore, FDA studies had found that problems with dilution were the greatest cause of adverse reaction with Botox. A review of the submitted paper uncovered serious problems and contradictory data, including graphs which suggested a worsening of wrinkle severity from baseline after the Botox wore-off. Additionally, small sample size and adverse events in the larger dilution groups were noted. In light of these concerns, the article was rejected for publication. The authors then resubmitted this article but removed the data which suggested wrinkles worsened after the toxin wore off. I spoke to the editor of the journal and once aware, he promised to address the problem with the authors. Two years later, in a special issue of the Journal (Dermatologic Surgery), sponsored by Allergan, this article was published with the altered data and the conclusion that dilution was unimportant.
When this was brought to the attention of David Pyott, Allergan’s chief executive, he stated that while they financially supported the issue and the foreign physician who authored the piece (their chief consultant or aesthetic Czar), they could do nothing about the altered data. In another article in the same issue of Dermatologic Surgery, this very same foreign physician attempted to include my name and another physician’s name on an article regarding the supposed safety of an injectable type B toxin. We both demanded our names be removed. We were then offered $10,000.00 by Soltace who manufactured the toxin (Myobloc) to include our names on this paper. This is supposedly the same sum they paid the lead author. We both voiced concern that this article was incomplete and did not reflect the true toxicity of this agent as had been in other studies, including Japanese studies that have shown this toxin to be much more toxic than originally believed. In clinical use, this toxin had been known to cause distant side effects such as dysphagia (inability to swallow) when it was used in normal doses.
Our names were removed from the article but the manufacturer refused to include this important safety data. The article concluded that this toxin was both safe and effective. The field of aesthetics has been badly damaged by these deliberate acts. I have voiced my serious concerns and raised questions about the alteration of data published in peer-reviewed journals and as a result, I have been terminated from one manufacturer’s advisory board and from the editorial board of a peer-reviewed publication (Dermatologic Surgery). Interestingly enough, William Coleman who was editor during the entire altered episode, remains at the helm of Dermatologic Surgery. Somehow and in some way, we must warn the public of the potential danger that exists at the end of the needle.
Arnold William Klein MD
Professor of Dermatology and Medicine
David Geffen School of medicine at UCLA
Arnold Klein Chair in Dermatology at UCLA
March 14th, 2009 at 6:13 pm
Part 2:
WORLD-RENOWNED DERMATOLOGIST REVEALS HISTORY OF FORGED DATA IN THE STUDY OF BOTOX
LOS ANGELES, March 16, 2009 – The recent news of Dr. Scott S. Reuben’s faked data for 21 studies involving Vioxx, Celebrex and other drugs has caused a ruckus in the medical world. But this isn’t the first case of forged data being released by a physician or physicians with strong ties to the pharmaceutical industry. For Dr. Arnold William Klein, the international authority on minimally invasive aesthetics and renowned for pioneering the cosmetic use of Botox and dermal fillers, it’s just a reminder of what’s happened to him and what he’s been trying to disclose to the public for several years. With no avail.
For the thousands of users of Vioxx and Celebrex, perhaps the most disturbing aspect of Reuben’s scandal is that many of the drugs he researched have been linked to serious side effects. For Dr. Klein, this is all too familiar, but the severe adverse reactions he’s witnessed have been associated with the use of botulinum toxins. And what’s most shocking for Dr. Klein is the discovery that articles written about agents such as Botox are totally incorrect and rely on falsified data. Such as in the case of Dr. Reuben.
According to Dr. Klein, “A few years back, the lead consultant for the company Allergan, which manufactures Botox, attempted to publish a manuscript that supported the concept that dilution of the agent did not matter. It has long been known that large dilutions of the vial of toxin could result in the toxin migrating and reaching unintended muscles. Furthermore, FDA studies had found that problems with dilution were the greatest cause of adverse reaction with Botox.”
“A review of the submitted paper uncovered serious problems and contradictory data,” says Dr. Klein, “including graphs which suggested a worsening of wrinkle severity from baseline after the Botox wore-off. Additionally, small sample size and adverse events in the larger dilution groups were noted. In light of these concerns, the article was rejected for publication. The authors then resubmitted this article but removed the data that suggested wrinkles worsened after the toxin wore off.”
“I spoke to the editor of the journal,” says Dr. Klein, “and once aware, he promised to address the problem with the authors. Two years later, in a special issue of the journal Dermatologic Surgery, sponsored by Allergan, this article was published with the altered data and the conclusion that dilution was unimportant. When this was brought to the attention of David Pyott, Allergan’s chief executive, he stated that while they financially supported the issue and the foreign physician who authored it, they could do nothing about the altered data. In another article in the same issue of Dermatologic Surgery, this very same foreign physician attempted to include my name and another physician’s name on an article regarding the supposed safety of an injectable type B toxin. We both demanded our names be removed. We were then offered $10,000.00 by Soltace who manufactured the toxin (Myobloc) to include our names on this paper. This is supposedly the same sum they paid the lead author. We both voiced concern that this article was incomplete and did not reflect the true toxicity of this agent as had been in other studies, including Japanese studies that have shown this toxin to be much more toxic than originally believed. Our names were removed from the article,” continues Dr. Klein, “but the manufacturer refused to include this important safety data. The article concluded that this toxin was both safe and effective.”
From his office on Roxbury Drive in Beverly Hills, Dr. Klein maintains a very busy, prestigious practice, catering to some of Hollywood’s biggest stars. He is recognized as the international father of architectural facial restoration. But none of this changes the fact that he’s become persona non-gratis at U.S. society meetings and speaking engagements. “I have voiced my serious concerns and raised questions about the alteration of data published in peer-reviewed journals, and as a result, I have been terminated from one manufacturer’s advisory board and from the editorial board of a peer-reviewed publication,” says Dr. Klein. “Maybe they don’t want anyone to question how they are re-writing history or making a very useful toxin potentially dangerous. I, for one, will not be quiet. It’s not enough to do no harm; one must do good.”
March 14th, 2009 at 8:00 pm
This release I just posted is a rewrite of my original release in part – however, the second part deals with problems with Myobloc, a Type B toxin. I think it is very important to reveal the truth about this situation to the public and to physicians. Sincerely and thankfully, Arnold Klein