BOTOX® and Botulinum Toxin Products to Bear Black Box Warning

The FDA issued a requirement for black box labeling on Allergan, Inc. Botox® and Botox Cosmetic®, Solstice Neruoscience’s Myobloc®, and Ipsen’s Dysport®, the newest formulation of botulinum toxin. Hospitalizations and deaths due to botulism poisoning have been reported, although a WebMD article of April 30, 2009 reports that the “Deaths among adults are suspected but could not be confirmed.†This report also states that no serious side effects have been confirmed due to cosmetic uses of Botox® and Myobloc®.

The key word in the above statements is “confirmed†as there have been a large number of reports filed. The decision to require the black box warning resulted from hospitalizations, including deaths of children with cerebral palsy who received botulinum toxin to treat muscle spasms. While reports indicate that the danger is associated with the higher doses used in therapeutic treatments, other reports suggest that cosmetic uses, especially the off-label uses have resulted in serious adverse reactions.

How bad can it get?

The FDA’s Adverse Event Database (AERS) reports 180 adverse events, of which there were 16 deaths. Many more are posted online from the European Union (EU). As of November 2005 693 cases were reported throughout its 27 member nations of which there were 17 deaths due to aspiration pneumonia.

The most common adverse events result from the toxin spreading from the injection site to distant sites where it has caused incontinence, drooping eyelids, double or blurred vision, difficulty talking, hoarseness, dry mouth, muscle weakness, breathing difficulties, and dysphagia (difficulty swallowing,) which leads to aspiration pneumonia due to weakness of the epiglottis and esophageal muscles. Weakened esophageal muscles can’t prevent reflux, and a weakened epiglottis doesn’t close off the airway sufficiently and allows stomach contents, or food or drink to enter the upper airways and lungs, a potentially fatal condition known as aspiration pneumonia.

Approved uses of botulinum toxin

There are two approved uses of botulinum toxin drugs. The first is therapeutic, primarily to treat cervical dystonia (uncontrolled muscle spasms in the neck and shoulder.) The second is cosmetic, to reduce frown lines between the eyebrows, or to treat excessive underarm sweating. Most cosmetic use of Botox® is not FDA approved and is considered off-label. Off-label uses of Botox® include injections in unapproved sites as well as in multiple sites.

According to the FDA, if the drug is used as descried on the label the likelihood of adverse reactions is near zero. Myobloc® is approved only for cervical dystonia. Because of dosage differences and type differences (Botox® is a type A and Myobloc® is a type B toxin) switching from one manufacturer’s formulation to another is a potential risk that can result in an overdose with the toxin spreading to unintended muscles.

The black box warning is accompanied by requirements to inform users in writing that botulinum toxin products have the potential for distant spread at the time of their injection. Manufacturers are to warn doctors and patients about the dangers of overdosing by substituting different botulinum products. Manufacturers are also to follow the outcomes of children and adults who receive their botulinum toxin drugs for involuntary muscle movement, and to submit safety data to the FDA.

About the Author

If you have received treatment from any botulism drug for cosmetic or therapeutic purposes and have experienced any of the above symptoms (even weeks after treatment) please visit the website of Schlichter, Bogard & Denton, experienced pharmaceutical attorneys.

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