The US Food and Drug Administration (FDA) has received several reports of side effects, including respiratory problems and death following the use of botulinum toxins types A and B for both FDA-approved and unapproved use.
The reactions reported are suggestive of botulism. This happens when the botulinum toxin found in cosmetic injections like Botox spreads in the body beyond the site where it was injected.
Most of the serious cases that resulted in hospital visits, severe respiratory trouble and death occurred in children who were treated for cerebral palsy-associated limb spasticity. The use of botulinum toxins to treat arm and leg muscle spasms is not an approved use of the substance 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. The FDA is currently reviewing safety data from clinical studies submitted by the manufacturers of Botox, Botox Cosmetic and Myobloc.
The 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. The 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 like Botox 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.
- 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 toxin.
- Understand that these effects have been reported as early as one day and as late as several weeks after treatment.
- 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 this data so far?
The FDA has reviewed 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. Doses for Botox 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. Doses for Botox ranged from 100 to 700 Units and for Myobloc from 10,000 to 20,000 U.