In a statement released yesterday, the Justice Department and Allergan announced that the drug maker will plead guilty to one misdemeanor charge of "misbranding" in which Allegan provoked doctors to use Botox off-label for “headache, pain, spasticity, and cerebral palsy in children,” said the AP. Off-label uses are not approved by the U.S. Food and Drug Administration (FDA); however, while physicians are free to prescribe approved drugs for nonapproved uses, it is illegal for drug makers to market approved medications for nonapproved uses.
Last April, the FDA mandated a black box label for Botox and similar products, warning of the risk of adverse events when the effects of a botulinum toxin injection spread beyond its injection site. The label revision followed an FDA safety review prompted by reports of adverse reactions that resembled botulism infections in patients receiving injections. The most serious cases involved hospitalization and death, and occurred mostly in children treated for cerebral palsy (CP)-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.
As part of the plea, Allergan said it would pay $375 million, which includes forfeiture of $25 million in assets, as well as $225 million in civil fines, said the AP. This includes $210 million to the federal government—the rest to a number of states—connected to the probe, said the AP. Allergan denies liability for the civil claims, added the AP.
In a related deal, Allergan, will submit compliance reports to the Department of Health and Human Services' Office of the Inspector General and will post physician payments, including honoraria, travel, or lodging, on its website, said the AP. Allergan "paid kickbacks to induce physicals to inject Botox for off-label uses and Allergan also taught doctors how to bill for off-label uses, including coaching doctors how to miscode Botox claims leading to millions of dollars of false claims being to submitted to federal and state programs," Assistant Attorney General Tony West said, quoted the AP.
"The FDA had approved therapeutic uses of Botox for only four rare conditions, yet Allergan made it a top corporate priority to maximize sales of far more lucrative off-label uses that were not approved by the FDA," said Sally Yates, U.S. Attorney for the Northern District of Georgia, quoted the AP. "Allergan further demanded tremendous growth in these off-label sales year after year, even when there was little clinical evidence that these uses were effective."
A whistleblower complaint led to the probe; the five whistleblowers will split $37.8 million of the government's settlement, explained the AP.
Earlier this year we wrote that a Botox overdose was blamed for the death of a seven-year-old Kristen Spears, who died in November 2007 of respiratory failure and pneumonia after receiving Botox injections to treat her severe CP. Her mother filed a lawsuit against Allergan. According to the lawsuit, Kristen began receiving Botox injections when she was six to calm CP-related leg spasms. Experts hired by Kristen’s mother said Kristen died because Botox weakened the muscles controlling her breathing and swallowing, leading to respiratory failure and pneumonia. The lawsuit alleged Allergan knew problems had been reported at least two years before her death.
Kristen’s mother also claimed Allergan encouraged Kristen’s doctor to treat CP patients with Botox and helped with his training, According to the LA Times, Kristen’s doctor testified in a deposition that he learned to use Botox on children with CP at Allergan-sponsored seminars in 2000 and 2001, adding that an Allergan sales rep visited his practice 50 times where they discussed treating juvenile CP patients.
Last April, the U.S. Food & Drug Administration (FDA) mandated a black box label for Botox and similar products that warned of the risk of adverse events when the effects of a botulinum toxin injection spreads beyond the site where it was injected. The label revision followed an FDA safety review prompted by reports of adverse reactions that resembled botulism infections 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. However, doctors are permitted to use approved drugs in anyway they see fit.
According to a lawsuit filed by the mother of Kristen Spears, her daughter began receiving Botox injections when she was six to calm spasms in her legs caused by severe cerebral palsy. Experts hired by Kristen's mother say that the girl died because Botox weakened muscles that controlled her breathing and swallowing, leading to respiratory failure and pneumonia.
The lawsuit alleges that Allergan knew problems had been reported at least two years before Kristen died. Her mother also claims that the drug maker encouraged Kristen's doctor to treat cerebral palsy patients with Botox and helped with his training, According to the Los Angeles Times, Kristen's doctor has testified in a deposition that he learned to use Botox on children with cerebral palsy at Allergan-sponsored seminars in 2000 and 2001. He also said that an Allergan sales rep visited his practice 50 times where they discussed treating juvenile cerebral palsy patients.
Other documents detailed by the Times also indicate that Allergan was receiving reports about problems caused by Botox while Kristen was receiving her treatments. For example, in 200 Allergan sent a confidential report to the FDA, saying that an analysis identified 38 patients who had suffered seizures after Botox injections. Twenty were children, and most had cerebral palsy.
In 2007, a consulting firm provided Allergan with a confidential report that identified 207 patients with medical problems, including several deaths, associated with the spread of toxin. Proportionally, more problems were reported among children who received Botox to treat problems like muscle spasms, the Times said.
While Allergan was receiving these reports, Kristen was administered seven Botox treatments in a 15 month period, starting in June 2006. According to the Los Angeles Times, her health began to fail, and she was hospitalized 10 times for breathing and swallowing problems, as well as pneumonia. She died just six weeks after her last treatment at the age of 7.
Using a drug in a way that has not been approved by the FDA is known as off-label use. As we've reported in the past, doctors are free to prescribe off-label, but the Food, Drug and Cosmetic Act of 1938 prohibits drug makers from promoting such uses. According to The Wall Street Journal, they may provide doctors with accurate information about off-label uses - such as scientific studies - if a doctor requests such material.
Critics of off-label promotion say such marketing practices are harmful, as the vast majority of off-label uses have not been subjected to enough scientific scrutiny to ensure their safety. Even so, off-label prescribing is common. According to The Wall Street Journal, a 2006 study in the Archives of Internal Medicine found that 21% of drug use is off-label.
When drug makers do promote off-label uses, they can get in a lot of trouble. For example, last month we reported that Pfizer had agreed to a $2.3 billion settlement with the U.S. Department of Justice to resolve allegations that it had illegally marketed several drugs including the antipsychotic Geodone, the pain killer Bextra; Zyvox, an antibiotic; and Lyrica, an anti-epileptic drug. That agreement marked the largest healthcare fraud settlement in the history of the U.S. Department of Justice.
Allergan's Botox is approved to treat facial wrinkles, eye muscle disorders and excessive underarm sweating. According to Reuters, Allergan is currently testing Botox for a variety of uses including treatment for upper limb spasticity in stroke victims as well as for migraine headaches.
In April, the FDA mandated a boxed warning for Botox and other botulinum toxin injection treatments regarding the risk of adverse events when the effects of the drugs spread beyond the injection site. The most serious cases had outcomes that included hospitalization and death, and occurred mostly in children treated for muscle-spasm conditions, an off-label use.
In a statement, the company said the FDA's ban on off-label promotion was particularly difficult since the agency had required the Botox safety update. "To ensure that physicians are equipped to treat patients as safely and successfully as possible, Allergan believes it is important to proactively provide comprehensive information to physicians about these off-label uses, such as dosing guidelines, patient selection criteria and proper injection technique," the company's statement said. "Without judicial relief, Allergan is unable to engage in a truthful and relevant information exchange with the medical community for fear of prosecution."
Reuters is reporting that Allergan has also maintained that its lawsuit against the FDA is not in response to a federal investigation into Botox marketing that was launched by federal prosecutors last year.
TPSG admitted that, with intent to mislead, it injected patients with Botulinum Toxin Type A manufactured by Toxin Research International, Inc. of Arizona ("TRI-toxin”) misbranded under the name of another drug, namely Botox /Botox Cosmetic. Five physicians, the practice administrator, and the Supervisory Nurse of TPSG pled guilty to strict-liability misdemeanor misbranding violations arising from the same conduct in 2004.
TPSG entered its guilty plea to felony charges and will be sentenced on December 14, 2009 in Albany. TPSG faces a fine of up to $500,000 and an order to pay restitution to about 150 patients who paid a total of approximately $100,000 for TRI-toxin injections while believing they were being treated with genuine Botox . The following pled guilty and face up to one year in prison and fines of up to $100,000 at sentencing:
Dr. William F. DeLuca, Jr., 58 of Latham, New York;
Dr. Steven Lynch, 65 of Slingerlands, New York;
Dr. Douglas M. Hargrave, 56 of Delmar, New York;
Dr. John D. Noonan, 62 of Slingerlands, New York;
Dr. Jeffrey L. Rockmore, 42, of Delmar, New York;
Practice Administrator Peter M. Slattery, 48 of West Sand Lake, New York; and
Supervisory Nurse Susan Knott (nee: Cole), 49, of Latham, New York.
Gary Tunkavige, Acting Special Agent-in-Charge of the FDA’s Office of Criminal Investigations and Office of Chief Counsel, said, “The FDA will continue to work tirelessly, on its own and in cooperation with the Department of Justice, to prevent and deter the illegal sale and use of unlicensed and unapproved drugs.”
United States Attorney Andrew T. Baxter said, “The Plastic Surgery Group of Albany misled about 150 patients who believed they were being treated with FDA-approved Botox when, in fact, they were being injected with a cheaper, unlicensed substitute. The dispositions announced today reflect a considered assessment of the nature and seriousness of that criminal conduct in the context of the positive contributions that the doctors and employees of this plastic surgery group have otherwise made to the Albany community over many years.”
An attorney for TPSG said that the group admitted that, starting in approximately February 2004, TPSG stopped using the FDA-approved Botox and Botox Cosmetic on its patients seeking treatments with Botulinum Toxin Type A for facial wrinkles and instead—from in or about February 2004 though December 2004—TPSG injected approximately 150 patients with TRI-toxin, which had not been approved by the FDA for use on humans. TPSG never disclosed to any patient that they were being injected with a product other than Botox or Botox Cosmetic.
In fact, noted the DOJ in its release, TPSG repeatedly misled patients into believing they were being treated with an FDA-approved Botox substance, for example, through the use of the Botox name on various brochures, promotional materials, consent forms, and invoices provided to patients. Patients were charged the same, higher cost of Botox treatments, for the cheaper, unapproved TRI-toxin.
The boxed warning cautions that botulinum toxin effects may spread from the area of injection to other areas of the body, causing symptoms similar to those of botulism. Those symptoms include potentially life threatening swallowing and breathing difficulties and even death. For the most part, these dangerous, sometimes deadly symptoms have been reported in children with cerebral palsy who were being treated with the botulinum toxin for muscle spasticity, a nonapproved, off-label use of the drug. Symptoms have also been reported in adults treated both for approved and unapproved uses.
The affected products are: Botox (new established name: onabotulinumtoxinA); Botox Cosmetic (new established name: onabotulinumtoxinA); Myobloc (new established name: rimabotulinumtoxinB); and Dysport (abobotulinumtoxinA), which was approved in April 2009 with the boxed warning and is not making name or label changes at this time.
No definitive serious adverse event reports of distant spread of toxin effect have been associated with dermatologic use of Botox/Botox Cosmetic at the recommended doses for frown lines between the eyebrows or severe underarm sweating. Also, no definitive serious adverse event reports of distant spread of toxin effect have been associated with Botox when used at approved doses for eyelid twitches or crossed eyes.
The FDA warns that the revised labels emphasize that the different botulinum toxin products are not interchangeable because the units used to measure the Botox/Botox Cosmetic products are different. To help reduce the potential for dosing errors, the botulinum toxin products have new established drug—also known as, “generic”—names. Neither the brand names nor the product formulations have changed.
We reported that last February, the FDA launched a safety review of botulinum toxin injections, including Botox and Botox Cosmetic. The FDA said, at the time, that it had received reports of adverse reactions that resembled botulism infections in patients receiving the injections. The most serious cases had outcomes that included hospitalization and death, and occurred mostly in children treated off-label for cerebral palsy-associated limb spasticity. The FDA said that adverse reactions may have been due to overdosing.
Earlier this year, the agency announced that all botulinum toxin injection products, including Botox and Botox Cosmetic, would carry a Black Box warning regarding the risk of adverse events when the effects of a botulinum toxin injection spreads beyond the site where it was injected. In addition to the new warning, the agency also required the makers of these drugs to develop and implement a Risk Evaluation and Mitigation Strategy [REMS] plan to provide more information regarding the risk for distant spread of botulinum toxin effects after local injection, as well as information to explain that botulinum toxin products cannot be interchanged. The REMS would also include a Medication Guide that explains the risks to patients, their families, and caregivers.
Allergan markets two Botox products. Botox Cosmetic is made from botulinum toxin type A, and is approved for temporary improvement in the appearance of moderate to severe facial frown lines. It is different from Botox, another Allergan botulinum toxin product, which is approved to treat conditions such as blepharospasm (spasm of the eyelids), cervical dystonia (severe neck muscle spasms), and severe primary axillary hyperhydrosis (excess sweating).
Last February, the FDA launched a safety review of botulinum toxin injections, including Botox and Botox Cosmetic. The FDA said at the time that it had received reports of adverse reactions that resembled botulism infections in patients receiving the injections. The most serious cases had outcomes that included hospitalization and death, and occurred mostly in children treated off-label for cerebral palsy-associated limb spasticity. The FDA said that the adverse reactions may have been due to overdosing.
Late last month, the agency announced that all botulinum toxin injection products, including Botox and Botox Cosmetic, would carry a Black Box warning regarding the risk of adverse events when the effects of a botulinum toxin injection spreads beyond the site where it was injected. In addition to the new warning, the agency is also requiring the makers of these drugs to develop and implement a Risk Evaluation and Mitigation Strategy [REMS] plan to provide more information regarding the risk for distant spread of botulinum toxin effects after local injection, as well as information to explain that botulinum toxin products cannot be interchanged. The REMS would also include a Medication Guide that explains the risks to patients, their families, and caregivers.
According to Reuters, the FDA wants to review Allergan's proposed REMS for Botox before making a decision on its application for expanding its use. The agency is also seeking additional documentation and analysis of a clinical study included in the approval application. Finally, the FDA has also proposed certain label revisions, including one that could broaden Botox use to upper limb spasticity regardless of underlying cause, Reuters said.
The FDA is not requiring that Allergan conduct additional clinical trials for the new use of Botox , something that could have delayed the agency's decision by years, Reuters said. The company told Reuters that it could comply with the FDA's request within 60 to 90 days.
Like Botox and Botox Cosmetic, Dysport is made from botulinum toxin type A. It was approved by the FDA yesterday as both an anti-wrinkle treatment, and for treating spasms of the neck muscles. The drug is manufactured by Medicis Pharmaceutical Corp. of Scottsdale and its partner, France’s Ipsen SA. The cosmetic version of Dysport should be available in the U.S. within the next 30 to 60 day. The medical form should be available during the second half of the year.
Late last year, we reported that the Australian Federal Health and Ageing Department had released documents detailing the case of a baby who was born deaf and blind in November 2005 after the mother was given facial cosmetic injections of Dysport in the first week of pregnancy. A 2006 report on the Australian birth defect case, written by the medical services manager for Ipsen, admitted a “possible” link with the drug’s use.
A month later, the Cosmetic Physicians Society of Australasia (CPSA) told its physicians to avoid using Dysport and similar products on pregnant women. “Botulinum toxin should not be prescribed to pregnant women and we advise our members to strictly follow these guidelines,” said the CPSA’s Dr Gabrielle Caswell said in a statement. “. . . there are some circumstances, such as during pregnancy, breastfeeding, glaucoma and neuromuscular disease where it is not an appropriate medication.”
The same day the FDA approved Dysport, it ordered the manufacturers of botulinum toxin injection products to add black box warnings Osmosis Jones trailer The Way We Were dvdrip - the agency's strictest safety alert - to their labels regarding their risk of potentially life-threatening complication when the effects of the toxin spread far beyond the injection site. According to the FDA, such an occurrence can cause symptoms similar to those of botulism, including unexpected loss of strength or muscle weakness, hoarseness or trouble talking, trouble saying words clearly, loss of bladder control, trouble breathing, trouble swallowing, double vision, blurred vision and drooping eyelids. The agency said such symptoms have mostly been reported in children with cerebral palsy being treated with the products for muscle spasticity, an unapproved use of the drugs. Symptoms have also been reported in adults treated both for approved and unapproved uses.
The new warning label will apply to Dysport, as well as Allergan's Botox and Botox Cosmetic and Solstice Neurosciences' Myobloc. Botox Cosmetic is approved as a wrinkle treatment. Myobloc and Botox are approved for the treatment of spasms of the neck muscles. Botox is also approved for the treatment of severe underarm sweating (primary axillary hyperhidrosis), crossed eyes (strabismus), and abnormal tics and twitches of the eyelids (blepharospasm).
The new black warning will apply to several products. Botox, which is made with botulinum toxin type A, 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, which also uses botulinum toxin Type A, is approved for temporary improvement in the appearance of moderate to severe facial frown lines. A third product, Myobloc, is made from botulinum toxin Type B and is approved for the treatment of adults with cervical dystonia. The new black box warning will also apply to Dysport, a botulinum toxin product that was just approved for use in the U.S. by the FDA today.
Last February, the FDA launched a safety review of botulinum toxin injections, including Botox and Botox Cosmetic. The FDA said at the time that it had received reports of adverse reactions that resembled botulism infections 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.
In addition to the new black box warning, the FDA said today that it will require that manufacturers develop and implement a Risk Evaluation and Mitigation Strategy [REMS], including a communication plan to provide more information regarding the risk for distant spread of botulinum toxin effects after local injection, as well as information to explain that botulinum toxin products cannot be interchanged. The REMS would also include a Medication Guide that explains the risks to patients, their families, and caregivers.
The FDA also said today that it is requiring the manufacturers to submit safety data after multiple administrations of the product in a specified number of children and adults with spasticity to assess the signal of serious risk regarding distant spread of toxin effects.
The widespread, off-label use of Botox to treat everything from headaches to oily skin has many patient advocates worried. According to The New York Times, they are concerned that many off-label Botox procedures could hold hidden risks, as such therapies have not undergone extensive study.
Botox and Botox Cosmetic, both manufactured by Allergan, are purified forms of botulinum toxin, a nerve poison produced by the bacteria. Botox Cosmetic is approved for treating moderate to severe facial frown lines. Botox is medically approved for treating blepharospasm (involuntary blinking of the eye), cervical dystonia (involuntary contractions of the neck muscles), hyperhidrosis (excess sweating), and strabismus (crossed eyes).
According to The New York Times, many doctors believe that Botox is an effective therapy for other ailments. Physicians have used it to treat chewing problems, swallowing problems, pelvic muscle spasms, drooling, hair loss, anal fissures and pain from missing limbs, the Times said.
Such use is known as "off-label", and is entirely legal. Once a drug is approved by the Food & Drug Administration (FDA), physicians are free to use it any way they see fit. The Times report said as much as half of all Botox procedures are off-label.
But Botox is not without risks. Last February, the FDA launched a safety review of botulinum toxin injections, including Botox and Botox Cosmetic. 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.
The consumer advocacy group, Public Citizen has petitioned the FDA to issue warnings to doctors about the hospitalizations and deaths associated with the use of botulinum toxin products. The group wants a “black box” added to product labels and an information pamphlet given to patients when the drug is injected.
Sidney Wolfe, director of Public Citizen, told The New York Times, that the safety of off-label Botox procedures have not been established. Such therapies amount to "trial and error with a nerve poison", Wolfe said.
According to the Times, when complications have occurred during off-label Botox procedures, they are often the result of overdosing. Because off-label treatments haven't been subjected to clinical trials, physicians often make an educated guess about dosing. But too much Botox can be toxic.
Obviously, Allergan sees other uses for Botox. With annual sales of $1.3 billion, Botox and Botox cosmetic have been big revenue generators for the company. According to The New York Times, Allergan has applied for patents on more than 90 uses for the drug. This year, it will ask the FDA to approve Botox as a treatment for stroke victims suffering from limb tightness or spasms. It is also expected to soon seek approval to market it as a treatment for migraine headaches and enlarged prostate.
If such uses are approved, Botox could become an even bigger blockbuster for Allergan. According to the Times, sales of Botox could easily double within the next five to seven years.
Several botulinum toxin treatments are currently approved for use in the U.S. Botox, which like Dysport is made with botulinum toxin Type A, 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, which also uses botulinum toxin Type A, is approved for temporary improvement in the appearance of moderate to severe facial frown lines. Myobloc, which is made from botulinum toxin Type B, is approved for the treatment of adults with cervical dystonia.
Dysport is not currently approved as a treatment in the U.S. However, the drug's manufacturer has submitted an application to the U.S. Food & Drug Administration (FDA), and hopes to have approval from the agency to market the drug as a treatment for cervical dystonia by mid-2009. The maker of Dysport is also seeking approval for a version used to treat wrinkles called Reloxin.
Last month, the Australian Federal Health and Ageing Department released documents detailing the case of a baby who was born deaf and blind in November 2005 after the mother was given facial cosmetic injections of Dysport in the first week of pregnancy. A 2006 report on the Australian birth defect case, written by the medical services manager for Dysport manufacturer Ipsen, admits a “possible” link with the drug’s use.
On Tuesday, The Cosmetic Physicians Society of Australasia (CPSA) told its physicians to avoid using Botox and similar products on pregnant women. "Botulinum toxin should not be prescribed to pregnant women and we advise our members to strictly follow these guidelines," said the CPSA's Dr Gabrielle Caswell said in a statement. ". . . there are some circumstances, such as during pregnancy, breastfeeding, glaucoma and neuromuscular disease where it is not an appropriate medication."
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.
Earlier this week, the Australian Federal Health and Ageing Department released documents detailing the case of a baby who was born deaf and blind in November 2005 after the mother was given facial cosmetic injections of Dysport in the first week of pregnancy. A 2006 report on the Australian birth defect case, written by the medical services manager for Dysport manufacturer Ipsen, admits a "possible" link with the drug's use.
Several botulinum toxin treatments are currently approved for use in the U.S. Botox, which like Dysport is made with botulinum toxin Type A, 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, which also uses botulinum toxin Type A, is approved for temporary improvement in the appearance of moderate to severe facial frown lines. Myobloc, which is made from botulinum toxin Type B, is approved for the treatment of adults with cervical dystonia.
In February 2008, the U.S. Food & Drug Administration (FDA) announced that Botox, Botox Cosmetic and Myobloc would undergo a safety review following reports of serious side effects, including the deaths of some children. According to the FDA, most of the severe reactions occurred in children treated for limb spasticity associated with cerebral palsy, an off-label use of the drugs. At the time, the FDA said that many reported reactions resembled botulism, and occurred when botulinum toxin spread beyond the site where it was injected.
While Dysport is not currently approved as a treatment in the U.S, the drug's manufacturer has submitted an application to the FDA, and hopes to have approval from the agency to market the drug as a treatment for cervical dystonia by mid-2009. The maker of Dysport is also seeking approval for a version used to treat wrinkles called Reloxin.
All of the deaths occurred in people who had received Botox injections to treat medical conditions such as neck and muscle spasms. Using Botox to treat conditions like muscle spasms requires much higher doses than what is typically used to eliminate wrinkling.
This past 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.
In the U.S., the group Public Citizen has petitioned the FDA issue warnings to doctors about the hospitalizations and deaths associated with the use of botulinum toxin products. The group wants a "black box" added to product labels and an information pamphlet given to patients when the drug is injected.
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.
Botox Cosmetic is approved for treating moderate to severe facial frown lines. Botox is medically approved for treating blepharospasm (involuntary blinking of the eye), cervical dystonia (involuntary contractions of the neck muscles), hyperhidrosis (excess sweating), and strabismus (crossed eyes); Myobloc is only approved for the neck condition. Both injections are made with forms of the botulinum toxin, which blocks nerve impulses to muscles, relaxing them. In off-label use, a physician uses a drug to treat a condition for which it is not specifically approved but for which evidence suggests it will help.
Meanwhile, the lawsuit claims that Botox maker Allergan promotes "off label" use for treating patients with cerebral palsy and other conditions not approved by the Food and Drug Administration (FDA) and that Allergan fails to appropriately warn Botox users of the possibility of fatal and life-threatening injuries from Botox injections. Another physician, Alan Gold, MD, a plastic surgeon in Great Neck, N.Y., and president of the American Society for Aesthetic Plastic Surgery, says off-label use carries additional risk that consumers need to be aware of. Only three of the 11 plaintiffs received Botox for cosmetic purposes; the remainder were treated with Botox for other conditions. Plaintiffs complaints included droopy eyelids, numbness, headaches, and swallowing and breathing problems.
By January, Botox and Myobloc were linked to 16 deaths and more hospitalizations due to botulinum toxin spreading inside the bodies of those patients. In response, Public Citizen, a U.S. consumer group, called for stronger warnings on the drugs and asked U.S. authorities to require the strongest possible warning—the black box—to be included on Allergan Inc.'s Botox and Solstice Neurosciences Inc.'s Myobloc. In February, the FDA announced its ongoing evaluation of reports of adverse reactions such as respiratory problems and death following the use of Botox and Myobloc for approved and unapproved uses.
Public Citizen said it reviewed 180 FDA reports involving patients injected with Botox or Myoblo, which detailed muscle weakness, difficulty swallowing, or aspiration pneumonia, a serious condition caused by breathing a foreign material into the lungs. Sixteen cases were fatal and four of these involved children under 18; there were also 87 patient hospitalizations. Dr. Sidney Wolfe, director of Public Citizen's Health Research Group, said such problems could occur if botulinum toxin spreads from the injection site to places such as the esophagus, causing partial paralysis. Early symptoms of botulinum toxin include dry mouth, difficulty breathing or swallowing, slurred speech, drooping eyelids, and muscle weakness.
Botulinum toxin, which is produced by the bacterium Clostridium botulinum and is known commercially as Botox and Myobloc, is one of the most powerful nerve poisons known. Although best known for smoothing facial wrinkles, Botox is medically approved for treating cervical dystonia, or rigid neck muscles and is also used to treat stroke victims and medical conditions including excessive sweating. Myobloc is only approved for the neck condition. Both injections are made with forms of the botulinum toxin, which blocks nerve impulses to muscles, relaxing them. In children, Botox is used when neurological disorders are present, such as Cerebral Palsy. Injections are meant to allow the child to gain normal movement by weakening stronger muscles and strengthening weaker ones by forcing the stronger contracting muscles to relax. While experiencing the drug’s effects, physical therapists work with the child to develop the weaker muscles. Although not appropriate for all children with CP, the treatment may help some move normally. Recently, the toxin is being used off-label to treat unremitting overactive bladder problems that do not respond to other therapies.
Of the seven types of botulism, only two—A and B—are currently used medically. Of the products available in the United States, Botox and Botox Cosmetic are derived from botulinum toxin A and Myobloc from B. This February, the FDA—which continues its safety review of these products—notified the public about reports of ill effects associated with the drugs.
It has long been known that injecting botulinum can cause unwanted effects in nearby muscles; injections to smooth eye creases may cause temporary eyelid drooping; however, there are more serious concerns over systemic reactions, or effects on distant muscles. And, the FDA says that adverse effects do not always occur right away and may emerge weeks after treatment.
In addition to the 16 deaths, Public Citizen reviewed the FDA’s adverse-event reports and found 180 cases of serious effects like pneumonia and difficulty swallowing and breathing. In September 2005, the Centers for Disease Control and Prevention (CDC) reviewed 1,437 adverse reports: 406 after medical use of Botox—217 of them serious effects—and 1,031 after cosmetic use—36 serious. Reports detailed cases of muscle weakness, difficulty swallowing, or aspiration pneumonia, a serious condition caused by breathing a foreign material into the lungs. Wolfe said such problems could occur if botulinum toxin spreads from the injection site to places such as the esophagus, causing partial paralysis.
"In the early reports on polyalkylimide implant injections for cosmetic purposes, there were no significant signs of bioincompatibility (rejection of, or reaction to, the foreign material). Recent evidence disprove these statements, and so the complete safety of polyalkylimide implant gels can no longer be assured," wrote Dr. Jaume Alijotas-Reig, of Vall d'Hebron University Hospital and Autonomous University of Barcelona, and colleagues. The study assessed 25 patients who developed adverse effects 12 months or more after polyalkylimide implant injection. Adverse effects included swelling, hardening, and swollen or tender nodules (skin lesions) near the injection site, as well as systemic troubles such as fever, arthritis, and dry eyes or mouth.
"Eight patients were previously injected with another implant," the study authors wrote. "Tender inflammatory nodules were seen in 24 patients. Systemic or distant manifestations appeared in six cases. Laboratory abnormalities were found in 20 cases. After an average of 21.3 months of follow-up, 11 patients appeared to be free of adverse effects, and 10 still had recurrent bouts." The rate of these delayed adverse events is unclear, said the authors. Study findings were published in the May issue of the journal Archives of Dermatology. "Considering the increased use of polyalkylimide implants in European countries and in the United States, physicians should be aware that intermediate or delayed adverse effects can occur with polyalkylimide implants just as they can with collagen, polyacrylamide, polylactic acid or methacrylate (cosmetic fillers)," the authors wrote.
Meanwhile, the popular skin injection generally used to smooth wrinkles was linked to a number of hospitalizations and 16 deaths. Of the deaths, four of the victims of the poisonous Botox injections were children. An additional 87 people were hospitalized. Botox and Myobloc have been linked to the injuries and fatalities because the botulinum toxin spread inside the bodies of the patients, killing some and injuring others. The toxin spreading in the bodies of the children proved most serious, killing four children under the age of 16.
As well as deaths, there have been reported problems of muscle weakness and difficulty swallowing. And, American group Public Citizen says it has seen 180 reports sent to the US Food and Drug Administration (FDA) about Botox and Myobloc. Spokesman Dr. Sidney Wolfe—director of Public Citizen’s Health Research Group—said users should be told of early symptoms such as dry mouth, trouble breathing, slurred speech, or droopy eyelids, adding “Significantly improved warnings would increase likelihood of earlier medical intervention and could prevent complications, including death.” Reports detailed cases of muscle weakness, difficulty swallowing, or aspiration pneumonia, a serious condition caused by breathing a foreign material into the lungs.
Botox, which is made with botulinum toxin type A, is approved in the US 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, which also uses botulinum toxin Type A, is approved for temporary improvement in the appearance of moderate to severe facial frown lines. A similar drug, Myobloc, is made from botulinum toxin Type B, and is approved for the treatment of adults with cervical dystonia.
According to the FDA, there have been reports of Botox, Botox Cosmetic and Myobloc reactions that are suggestive of botulism, which occurs when botulinum toxin spreads in the body beyond the site where it was injected. 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.
Now, scientists from the Italian National Research Council's Institute of Neuroscience in Pisa who were conducting experiments with Botox in rats have found that the toxin can make its way to the brain in those lab animals. Although rats and humans have a different physiology and their responses may vary, the researchers said say the results should lead to more research.
In the study, the whisker muscles of rats were injected with the toxin. Within three days, the scientists discovered traces of potentially deadly botulism in the rodents' brain stems. The study's author, Matteo Caleo, said the toxin also moved from one hippocampus, which controls long-term memory and spatial navigation, to the hippocampus on the other side of the rat's brain. The botulism toxin was still present in the rats' brains after six months.
Last month, another Botox study conducted by researchers at the University of Calgary experimenting on cats also found that the botulism toxin from Botox could migrate to other parts of the body. The Calgary team injected the toxin into a muscle at the back of the leg of cats. Four weeks later, the time it takes for Botox to have its full effect, they measured the strength of this muscle, and that of a neighboring muscle. The Botox study revealed the toxin passed easily into the surrounding muscles and weakened all the muscles in the area. The results support other research that has already shown that botulinum can pass through tissue surrounding muscle.
Allergan, the California-based company that makes Botox, told the UK newspaper "The Daily Mail" that the Italian research was not conclusive and contradicted previous findings. "The authors used a laboratory preparation of botulinum toxin and did not use Botox," said a spokesman. "Data suggests that different preparations of botulinum toxin react differently in both the laboratory and in clinical practice."
Botox, which is made with botulinum toxin type A, is approved in the US 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, which also uses botulinum toxin Type A, is approved for temporary improvement in the appearance of moderate to severe facial frown lines. A similar drug, Myobloc, is made from botulinum toxin Type B, and is approved for the treatment of adults with cervical dystonia.
According to the FDA, there have been reports of Botox, Botox Cosmetic and Myobloc reactions that are suggestive of botulism, which occurs when botulinum toxin spreads in the body beyond the site where it was injected. 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.
It has been widely assumed that Botox stayed in the muscle after it was injected and was therefore safe - but new research contradicts this. In the study, conducted at the University of Calgary, in Canada, and published in the Journal of Biomechanics, it was found that the product is not as easy to control as previously thought. Experimenting on cats, the Calgary team injected the toxin into a muscle at the back of the leg. Four weeks later, the time it takes for Botox to have its full effect, they measured the strength of this muscle, and that of a neighboring muscle.
The Botox study revealed the toxin passed easily into the surrounding muscles and weakened all the muscles in the area. The results support other research that has already shown that botulinum can pass through tissue surrounding muscle.
Allegan, the company that makes Botox, insists that the drug is safe, and points to the fact that it has been in use for more than 20 years. Still, Botox recipients have been warned to seek immediate medical attention if they experience worsening or unexpected difficulty in swallowing or talking, trouble breathing or muscle weakness following any injection.
Botox and similar drugs are already at the center of a Food & Drug Administration (FDA) safety review. The review came after the FDA received reports of systemic adverse reactions including respiratory compromise and death following use of botulinum toxins types A and B for both FDA-approved and -unapproved uses. Botox and another drug, Myobloc have been linked to 16 deaths and more hospitalizations; reactions reported are suggestive of botulism in which the toxin spreads in the body beyond the injection site. The most serious cases involved hospitalization and death and occurred mostly in children treated for cerebral palsy-associated limb spasticity (severe arm and leg muscle spasms). Use of botulinum toxins for this purpose is not approved in the US in children or adults. The FDA is aware of the literature describing the use of botulinum toxins to treat limb spasticity; however, the safety, efficacy, and dosage of botulinum toxins have not been established for the treatment of limb spasticity of cerebral palsy or for use in any condition in children under 12.
Botox (botulinum toxin type A) is medically approved for treating cervical dystonia (rigid neck muscles), blepharospasm (eyelid spasm), and severe primary axillary hyperhydrosis (excess sweating). Botox Cosmetic (botulinum toxin Type A) is approved for temporary improvement in the appearance of moderate to severe facial frown lines. Myobloc (botulinum toxin Type B) is approved for the treatment of adults with cervical dystonia; the safety and effectiveness of Myobloc for cervical dystonia in children has not been established. The botulinum toxin blocks nerve impulses to muscles, relaxing them.
The FDA is reviewing data from clinical studies submitted by the manufacturers of Botox, Botox Cosmetic, and Myobloc, as well as post-marketing adverse event reports, and medical literature. Current labeling for Botox, Botox Cosmetic, and Myobloc describes adverse reactions occurring near the injection site for each product’s approved uses. The Warnings sections for the products note that important systemic adverse effects, including severe difficulty swallowing and breathing occurred in patients with neuromuscular disorders after local injection of typical. The FDA now has evidence that similar, potentially life-threatening events can occur following local injection in those with underlying conditions such cerebral palsy associated limb spasticity.
Until the FDA has completed its review, healthcare professionals who use medicinal botulinum toxins should understand that potency amounts indicated by “Units” or “U” differs among the products and are not comparable from one product to the next. They should also be alert to the potential for adverse effects and know effects have been reported as early as one day and as late as several weeks following treatment, providing patients and caregivers with the information to identify the signs and symptoms of these effects, especially worsening or unexpected difficulty swallowing or talking, trouble breathing, or muscle weakness.
Botox, which is made with botulinum toxin type A, 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, which also uses botulinum toxin Type A, is approved for temporary improvement in the appearance of moderate to severe facial frown lines. Myobloc, which is made from botulinum toxin Type B, is approved for the treatment of adults with cervical dystonia.
According to the FDA, it has received fewer than 100 reports of adverse events related to the use of botulinum toxin injections. But some say the real numbers are much higher. Public Citizen, a consumer advocacy group, petitioned the agency two weeks ago to strengthen warnings on the products' labels because of serious adverse reactions. "Our analysis of FDA data found that between Nov. 1, 1997, and Dec. 31, 2006, the makers of the drugs had reported 180 U.S. cases of people developing serious conditions after receiving injections," Sidney Wolfe, director of the Public Citizen Health Research, said in a statement Friday. Those 180 cases included 16 deaths, four of which occurred in children.
According to the FDA, the Botox, Botox Cosmetic and Myobloc reactions reported resemble botulism. The reactions have occurred when botulinum toxin spreads beyond the site where it was injected. 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 be due to overdosing
The FDA has advised that healthcare professionals who use medicinal botulinum toxins should understand that potency determinations expressed in “Units” or “U” are different among the botulinum toxin products; clinical doses expressed in units are not comparable from one botulinum product to the next. Physicians should also be alert to the potential for systemic effects following administration of botulinum toxins such as: dysphagia, dysphonia, weakness, dyspnea or respiratory distress and Understand that these effects have been reported as early as one day and as late as several weeks after treatment. Patients and caregivers should be provided with the information they need to be able to identify the signs and symptoms of systemic effects after receiving an injection of a botulinum toxin. Finally, healthcare providers should tell patients to receive immediate medical attention if they have worsening or unexpected difficulty swallowing or talking, trouble breathing, or muscle weakness.
Botox, which is made with botulinum toxin type A, 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, which also uses botulinum toxin Type A, is approved for temporary improvement in the appearance of moderate to severe facial frown lines. Myobloc, which is made from botulinum toxin Type B, is approved for the treatment of adults with cervical dystonia.
According to the FDA, the Botox, Botox Cosmetic and Myobloc reactions reported are suggestive of botulism, which occurs when botulinum toxin spreads in the body beyond the site where it was injected. 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.
According to the FDA, pediatric botulism cases occurred in patients less than 16 years old, with reported symptoms ranging from dysphagia to respiratory insufficiency requiring gastric feeding tubes and ventilatory support. Serious outcomes included hospitalization and death. The most commonly reported use of botulinum toxin among these cases was treatment of limb muscle spasticity associated with cerebral palsy. For Botox, doses ranged from 6.25 to 32 Units/kilogram (U/kg) in these cases. For Myobloc, reported doses were from 388 to 625 U/kg.
The reports of adult botulism cases described symptoms including patients experiencing difficulty holding up their heads, dysphagia and ptosis. Some reports described systemic effects that occurred distant from the site of injection and included weakness and numbness of the lower extremities. Among the adult cases that were serious, including hospitalization, none required intubation or ventilatory support. No deaths were reported. The doses for Botox ranged from 100 to 700 Units and for Myobloc from 10,000 to 20,000 U.
The FDA has advised that healthcare professionals who use medicinal botulinum toxins should understand that potency determinations expressed in “Units” or “U” are different among the botulinum toxin products; clinical doses expressed in units are not comparable from one botulinum product to the next. Physicians should also be alert to the potential for systemic effects following administration of botulinum toxins such as: dysphagia, dysphonia, weakness, dyspnea or respiratory distress and Understand that these effects have been reported as early as one day and as late as several weeks after treatment. Patients and caregivers should be provided with the information they need to be able to identify the signs and symptoms of systemic effects after receiving an injection of a botulinum toxin. Finally, healthcare providers should tell patients to receive immediate medical attention if they have worsening or unexpected difficulty swallowing or talking, trouble breathing, or muscle weakness.
The FDA said it is currently reviewing safety data from Botox, Botox Cosmetic and Myobloc clinical studies submitted by the drugs' manufacturers, as well as post-marketing adverse event reports and medical literature. After completing a review of the data, the FDA said it will communicate to the public its conclusions, resulting recommendations, and any regulatory actions.
Botox made news last week when the lobby group Public Citizen wrote to the U.S. Food and Drug Administration (FDA) calling on it to "immediately require Allergan and Solstice Neurosciences to issue a warning letter to physicians regarding all formulations of botulinum toxin (Botox and Myobloc, respectively). This letter would alert physicians to serious problems, including hospitalizations and deaths, resulting from the spread of the toxin from the site of injection to other parts of the body," they said. Public Citizen's petition included an in-depth analysis of hundreds of mild and severely adverse reactions to Botox treatments, which have been reported since the late 1990s in both Europe and the U.S.
Allergan disputed claims that complications from Botox treatments have resulted in death. In the U.S., consumer groups are demanding new black box warnings be included to Botox and Myobloc packaging to indicate the medications can cause death in some cases.
Health Canada said its primary concern is the health and safety of Canadians. If the review identifies any new safety information, "it will be made public to Canadians and Canadian health care professionals as soon as it is available."
But recently, Botox has been linked to a number of hospitalizations and 16 deaths. Of the deaths, four of the victims were children under the age of 16. An additional 87 people were hospitalized. All the deaths and injuries appear to be the result of the botulinum toxin spread inside the bodies of the patients.
Botox is best known for smoothing facial wrinkles but is medically approved for treating cervical dystonia, or rigid neck muscles and is also used to treat stroke victims and medical conditions including excessive sweating. Myobloc is only approved for the neck condition. Both injections are made with forms of the botulinum toxin, which blocks nerve impulses to muscles, relaxing them. In children, Botox is used when neurological disorders are present, such as Cerebral Palsy. Injections are meant to allow the child to gain normal movement by weakening stronger muscles and strengthening weaker ones by forcing the stronger contracting muscles to relax. While experiencing the drug’s effects, physical therapists work with the child to develop the weaker muscles. Although not appropriate for all children with CP, the treatment may help some move normally.
As well as deaths, there have been reported problems of muscle weakness and difficulty swallowing. And American group Public Citizen says it has seen 180 reports sent to the FDA about Botox and Myobloc detailing cases of muscle weakness, difficulty swallowing, or aspiration pneumonia, a serious condition caused by breathing a foreign material into the lungs.
Botox is best known for smoothing facial wrinkles, but the drug is also medically approved by the Food & Drug Administration (FDA) for treating cervical dystonia, or rigid neck muscles. In some cases, Botox is also used to treat stroke victims and other medical conditions including excessive sweating. Myobloc is only approved for the neck condition.
In children, Botox is used when neurological disorders are present, such as Cerebral Palsy. Injections are meant to allow the child to gain normal movement by weakening stronger muscles and strengthening weaker ones by forcing the stronger contracting muscles to relax. While experiencing the drug’s effects, physical therapists work with the child to develop the weaker muscles. Although not appropriate for all children with CP, the treatment may help some move normally.
Consumer groups are demanding new black box warnings be included to Allergan Inc.'s Botox and Solstice Neurosciences Inc.'s Myobloc packaging to indicate the medications can cause death in some cases.
As well as deaths, there have been reported problems of muscle weakness and difficulty swallowing. And American group Public Citizen says it has seen 180 reports sent to the FDA about Botox and Myobloc. Spokesman Dr. Sidney Wolfe—director of Public Citizen’s Health Research Group—said users should be told of early symptoms such as dry mouth, trouble breathing, slurred speech, or droopy eyelids, adding “Significantly improved warnings would increase likelihood of earlier medical intervention and could prevent complications, including death.”
Reports detailed cases of muscle weakness, difficulty swallowing, or aspiration pneumonia, a serious condition caused by breathing a foreign material into the lungs. Reports to the FDA do not prove a product caused a particular problem, but the agency uses the reports to find patterns of potential complications. "There are no safety issues raised in the petition that are not already addressed in the labeling for Botox," Allergan said, adding that it is in frequent dialogue with the FDA to ensure proper labeling and submits all information it receives on adverse events regardless of whether or not they are related to Botox. Solstice Neurosciences reported it recently provided safety data to the FDA and stood behind the drug’s current prescribing information. Wolfe said such problems could occur if botulinum toxin spreads from the injection site to places such as the esophagus, causing partial paralysis. Instructions for Botox and Myobloc mention the issue but it is easy to miss, he said.
Botox is best known for smoothing facial wrinkles but is medically approved for treating cervical dystonia, or rigid neck muscles; Myobloc is only approved for the neck condition. Both injections are made with forms of the botulinum toxin, which blocks nerve impulses to muscles, relaxing them.
Public Citizen said it reviewed 180 reports submitted to the Food and Drug Administration (FDA) by manufacturers involving patients injected with Botox or Myobloc. Reports detailed cases of muscle weakness, difficulty swallowing, or aspiration pneumonia, a serious condition caused by breathing a foreign material into the lungs. Reports to the FDA do not prove a product caused a particular problem, but the agency uses the reports to find patterns of potential complications.
"There are no safety issues raised in the petition that are not already addressed in the labeling for Botox," Allergan said, adding that it is in frequent dialogue with the FDA to ensure proper labeling and submits all information it receives on adverse events regardless of whether or not they are related to Botox. Solstice Neurosciences reported it recently provided safety data to the FDA and stood behind the drug’s current prescribing information.
Of the cases reported to the FDA, 16 were fatal. Of these, four involved children under 18. There were also 87 patient hospitalizations linked to the medication.
Dr. Sidney Wolfe, director of Public Citizen's Health Research Group, said such problems could occur if botulinum toxin spreads from the injection site to places such as the esophagus, causing partial paralysis. Instructions for Botox and Myobloc mention the issue but it is easy to miss, he said.
Public Citizen asked the FDA to order a black-box warning to highlight the concern, to draft a notice to doctors, and to require a consumer-friendly guide explaining the medicines’ risks to be distributed by doctors when administering the drugs. "These significantly improved warnings to doctors and patients would increase the likelihood of earlier medical intervention when symptoms of adverse reactions to botulinum toxin first appear and could prevent more serious complications, including death," Public Citizen said in a petition to the FDA.
Early symptoms of botulinum toxin include dry mouth, difficulty breathing or swallowing, slurred speech, drooping eyelids, and muscle weakness. The group said European regulators have warned physicians to watch for signs of botulinum toxin complications. FDA spokeswoman Karen Riley said the agency would not comment while the Public Citizen petition was under review.
In November, Allergan projected worldwide sales for Botox would top $1.1 billion in 2007. Allergan shares closed down 1.4 percent to $64.12 at the end of regular trading Thursday on the New York Stock Exchange.
According to the American Society of Dermatological Surgery, patients seeking treatment to treat or correct botched procedures is on the rise. The ASDS said that 41 percent of its members have seen an increase in patients seeking second treatments to repair damage from botched procedures performed by improperly trained individuals.
The ASDS said a physician should always perform cosmetic surgeries and procedures. Consumers considering cosmetic surgery should always ask about the training of the person who will perform the surgery. They should also ask what safety procedures are in place in case of an emergency. Consumers should also be wary about procedure prices that seem too good to be true, the ASDS said, €œThis is just one of those times when you just don €™t want to get a bargain. € The ASDS also warns consumers not to use physicians who aren't trained in performing these procedures. General doctors and gynecologists are offering these services more often, which could potentially expose them to medical malpractice lawsuits.