We want to begin by addressing recent media reports on botulinum toxins and what you need to know – the stories behind the headlines, if you will. In order to make choices about your health and wellbeing, you need facts, not misconceptions or alarmist conclusions.

Public Citizen and the FDA

In January 2008, national consumer advocacy group Public Citizen petitioned the FDA to warn patients and physicians about serious side effects associated with the use of botulinum toxins. The organization analyzed FDA data that included 658 adverse events, of which 180 were aspiration (fluid in the lungs), dysphagia (difficulty swallowing) and/or pneumonia. There were 16 deaths reported, four of which occurred in children under the age of 18. In response, the FDA issued an Early Communication announcing a pending safety review focusing on high-dose medical uses of botulinum toxins.

What You Need to Know

1. The posting of an Early Communication is routine and provides early information about safety or pending reviews. In the FDA’s own words, an Early Communication “does not mean that there is a causal relationship between the products and the adverse events.”

2. A report of an adverse event following treatment with a drug does not by itself mean that the drug caused the event – it just means that the event happened after treatment with the drug. A report is filed even if the physician has concluded that the drug did not cause the event.
 
3. Over a million people have been treated with Botox® for cosmetic use. In its entire history, there has never been a single reported death where a causal link to Botox Cosmetic® was established. None of the adverse events in the upcoming FDA review relate to a death involving the use of Botox Cosmetic®.

4. The FDA safety review involves a small number of adverse event reports involving large doses and focuses mainly on people who were already very sick with juvenile cerebral palsy and other lower-limb spasticities. Botox® has been used worldwide to treat a variety of often-serious medical conditions for 18 years and is approved in roughly 60 countries for the treatment of juvenile cerebral palsy (though not in the US). Specialists in the US have used botulinum toxins to treat cerebral palsy with great success for more than a decade at their own discretion (called “off-label” use).

5. There is a huge difference in dose between Botox® for medical purposes and for cosmetic injections in the face. In cosmetic procedures, doses usually range from 20 to 50 units at a time. The treatment of juvenile cerebral palsy involves very compromised, sick children and relatively huge doses — often up to a total of 700 units. In some of the adverse event reports, physicians used doses much higher than that approved for cerebral palsy outside the US, greater than 80 times that of a typical cosmetic injection on a per kilogram of body weight basis. According to Allergan, the makers of Botox®, “Our analysis indicates that when a problem arises in the use of the product for juvenile cerebral palsy, it tends to either be because the patient was already very high risk and sick and/or because a significant amount of Botox® was administered.”

For more information on the safety of Botox®, click here



Buyer Beware

In 2004, Toxin Research International (TRI) in Tucson, Arizona, began selling a substitute, “cheaper alternative to Botox®” to dozens of physicians in the US. The bogus Botox® was labeled “FOR RESEARCH PURPOSES ONLY, NOT FOR HUMAN USE.” Over 200 plastic surgeons, dermatologists, family physicians and naturopaths ordered the product from TRI. In December 2005, four people in Florida experienced a mysterious paralysis that put them on ventilators, unable to swallow or breathe, that was eventually linked to the Botox alternate, and investigators estimated that more than 1000 people may have been injected. Following an investigation by the FBI, the owners of TRI – naturopathic physicians Chad Livdah and his wife, Zahra Karim – were sentenced to 9 and 6 years in prison, respectively, and a number of other injectors have been convicted in the incident.

Other botulinum toxins not approved by the FDA, for example from China and Russia, among other places, have popped up in North America, and are sold at reduced prices. Some of these may even look like the real product. The problem with unapproved toxin is that it’s not as well controlled as the commercially available product nor as pure. In 2006, a woman in Salinas, California, died after receiving fake Botox® injections from her hairstylist.

Avoiding Fakes

• Choose properly trained and qualified cosmetic specialists (nothairstylists or spa technicians)
• Do your research; the cheapest choice is not the safest
• Check the vial of Botox® for a rainbow-coloured holograph with the name Allergan within the lines

Can Botox Spread to the Brain?

In April, a new study suggested that Botox® has the ability to travel along neurons and into the brain.[1]  Researchers in Italy injected botulinum toxin type A into the whisker muscles of rats and mice and found trace amounts of the toxin in the brainstem three days later.

To learn more about the misinformation about BOTOX click here.

Facts

1. The botulinum used in the Italian study was an uncomplexed toxin (140,000 kDa molecule Botox is complexed with other proteins as a 900,000 kDa complex) produced in the laboratory for veterinarian research purposes and is not approved for human use by any governing body. The clinical effect of uncomplexed toxin in humans is not well studied or understood, as yet.

2. The dose of the research animal neurotoxin injected into the whisker pads of rodents were at least 150 times higher (per body weight) than approved doses to treat frown lines in humans.

3. People are not rats; rodent physiology is remarkably different from that of humans. It is not possible to equate the results of a single rodent study to what might occur in humans.

4. The results of this study are at odds with nearly twenty years of research demonstrating the safety of Botox®. Botulinum toxin is one of the most researched drugs in the world. Multiple clinical trials established the safety of Botox® in humans nineteen years ago and led to the approval of the FDA, Health Canada, and 70 other regulatory bodies around the world.

The Safety of Botox

With over 3000 publications to date, Botox® is one of the most researched drugs in the world (see graph). In 2005, researchers analyzed 1031 adverse event reports submitted to the FDA for Botox®.[2]  Only 36 were considered “serious” (headaches, facial paralysis, muscle weakness, difficulty swallowing, flu-like symptoms, and allergic reactions), and 13 had underlying disease that may have contributed to the adverse event. Serious adverse events were most common with higher doses associated with medical, rather than cosmetic, Botox®. Even when used in the long-term for therapeutic uses, serious side effects are rare.[3]

Two studies published in 2007 examined the safety of multiple injections over many years. The first trial looked at over 4000 treatments in 945 people injected in the upper face and found only mild or moderate side effects, such as bruising and eyelid drooping, and side effects decreased with repeated injections.[4]  In our own study of 50 people, adverse events occurred in only 9 out of 853 treatments sessions and were mild to moderate and temporary.[5]

The Bottom Line

It is difficult to draw any conclusions from a single animal study – especially one that used higher doses of a non-Botox®, unapproved veterinary-grade drug — that seems to refute years of research and experience in humans. Botox Cosmetic® is not only safe, but extremely effective; in a recent survey by Allergan Inc., 97% of people injected with Botox Cosmetic were satisfied with the results of the procedure.
 
Parties, Cruises, and Bars

Years ago, when Botox® first arrived on the scene, some physicians made headlines when they began treating men and women at “Botox® parties.

“Both the American Society for Dermatologic Surgery and The American Society of Plastic Surgeons released a statement reminding consumers that Botox® “is still a medical procedure.” We think it prudent to re-state the  Societies’ recommendations for effective and safe Botox® treatment.

1. Check the Physician’s Credentials. Because of the complicated musculature of the human face, potential Botox® patients should seek a cosmetic surgeon certified in dermatology, ophthalmology, plastic surgery or ENT facial plastic surgery.

2. Seek a Complete Patient Evaluation. When a person is considering an elective medical treatment like Botox®, he or she should consult with a physician for an evaluation, as well as a full medical history, to determine the most appropriate treatment.
 
3. Be Informed. Speak with others about the procedure, friends, family as well as a physician. When a treatment decision is made co-operatively between the physician and patient, the physician should explain the factual information about risks, benefits, alternatives, and reasoning for the proposed treatment, after which an Informed Consent document should be signed by the patient. The consumption of alcohol before, during or after the medical procedure could affect a patient’s decision and outcome. The decision to have a medical procedure should be made without the influence of alcohol or peer pressure.

4. Choose an Appropriate Setting. Botox® injections should be performed in a setting with appropriate medical personnel and necessary equipment to safely observe patients and deal with potential complications, as well as provide for the disposal of medical waste as required by Occupational Safety.

[1] Antonucci F, Rossi C, Gianfranceschi L, Rossetto O, Caleo M. Long-distance retrograde effects of botulinum neurotoxin A. J Neurosci 2008;28:3689-96.

[2] Coté TR, Mohan AK, Polder JA, Walton MK, Braun MM. Botulinum toxin type A injections: Adverse events reported to the US Food and Drug Administration in therapeutic and cosmetic cases. J Am Acad Dermatol 2005;53:407–15.

[3] Naumann M, Albanese A, Heinen F, Molenaers G, Relja M. Safety and efficacy of botulinum toxin type A following long-term use. Eur J Neurol 2006;13 Suppl 4:35-40.

[4] Rzany B, Dill-Müller D, Grablowitz D, Heckmann M, Caird D Repeated botulinum toxin A injections for the treatment of lines in the upper face: a retrospective study of 4,103 treatments in 945 patients. Dermatol Surg 2007;33(1 Spec No.):S18-25.

[5] Carruthers J, Carruthers A. Complications of botulinum toxin A. Facial Plast Surg Clin North Am 2007;15:51-4.