January 3, 2009
December 2008
FDA warning issued in early February of 2008--have advised consumers of
newly learned risks that are associated with using the popular injections, Botox. Of the risks,
dangerous side effects such as respiratory failure and death have been warned of by the FDA.
This report has spurred the sales of other anti-wrinkle creams like Skinlastin. [1]

The common side effects include the loss of facial expressiveness, and the numbing or losing
of feeling in the muscles of areas near to where injections have been administered. Fatal side
effects are rare but serious including respiratory failure and death. [1]

Off-label Uses of Botox
However, a study done at the Headache Care Center, which was recently published, found that
patients who were unsuccessful with more traditional treatments were given back their quality
of life, with Botox. Patients get multiple injections at specific points in their forehead, neck and
other muscles. Doctors say the results typically last 3 to 4 months, unlike other medications
taken on a daily basis. Please, note that FDA hasn't approved Botox for treatment of
Migraines. [2]

Some physicians used Botox to stop muscle rigidity and spasms in cerebral palsy patients, but
the powerful drug can migrate inside the body and affect the muscles that control breathing,
causing death. In July 2008, a lawsuit was filed against Allergan Inc., Botox’s maker, on behalf
of the families of deceased victims and other victims, alleging the company promoted “off label”
uses of Botox, causing injuries and deaths. [3]
Early Communication about an Ongoing Safety Review Botox and Botox
Cosmetic (Botulinum toxin Type A) and Myobloc (Botulinum toxin Type B) FDA
February 8, 2008

FDA has received reports of systemic adverse reactions including respiratory
compromise and death following the use of botulinum toxins types A and B for both
FDA-approved and unapproved uses. The 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.

These serious systemic adverse reactions occurred following treatment of a variety of
conditions using a wide range of botulinum toxin doses.  FDA is currently reviewing
safety data from clinical studies submitted by the manufacturers of Botox, Botox
Cosmetic and Myobloc, as well as post-marketing adverse event reports and the
medical literature.

Botox (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, also 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 have
not been established.   

FDA is aware of the body of literature describing the use of botulinum toxins to treat
limb spasticity in children and adults.  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 less than 12 years of age.

The current prescribing information (labeling) for  Botox,  Botox Cosmetic and Myobloc
describes adverse reactions occurring in regions near the site of injection for each
product’s approved uses, such as dysphagia (difficulty swallowing) after injections to
treat cervical dystonia, or ptosis (drooping eye lids) after injections for glabellar frown
lines or for strabismus and blepharospasm.

Warnings sections of the labeling for both botulinum toxin products note that
important systemic adverse effects, including severe difficulty swallowing and difficulty
breathing have occurred in patients with neuromuscular disorders after local injection of
typical doses of botulinum toxin.  FDA now has evidence that similar, potentially life-
threatening systemic toxicity from the use of botulinum toxin products can also result
after local injection in patients with other underlying conditions such as those with
cerebral palsy associated limb spasticity. Systemic toxicity has been reported in
children, several of whom required feeding tubes and/or ventilation (breathing) support.

Until such time that FDA has completed its review, 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
* Be alert to the potential for systemic effects following administration of botulinum
toxins such as: dysphagia, dysphonia, weakness, dyspnea or respiratory distress
* Understand that these effects have been reported as early as one day and as late as
several weeks after treatment
* Provide patients and caregivers with the information they need to be able to identify
the signs and symptoms of systemic effects after receiving an injection of a botulinum
* Tell patients they should receive immediate medical attention if they have worsening
or unexpected difficulty swallowing or talking, trouble breathing, or muscle weakness

What does FDA know now about these data?

The FDA has reviewed post-marketing cases from its Adverse Event Reporting
System (AERS) database and from the medical literature of pediatric and adult
patients diagnosed with botulism following a local injection with a marketed botulinum
toxin product.

The 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.