botulinum toxin type A products: updated warnings regarding risk of iatrogenic botulism

Botulinum toxin type A (BoNT-A), onabotulinumtoxinA (Botox) was approved by the United States Food and Drug Administration for temporary improvement of glabellar lines in patients 65 years and younger in 2002 (1):

• theoretically, botulinum toxins weaken skeletal muscles by presynaptic blockade of the exocytosis of acetylcholine (ACh)-containing vesicles in the neuromuscular junction and eliminate facial wrinkles
• licensed indications for botulinum containing products vary by product and include neurologic disorders (e.g. focal spasticity, some types of spasms and chronic migraine), bladder disorders (e.g. overactive bladder), severe sweating of the axillae (hyperhidrosis) and for the temporary improvement in the appearance of facial lines where their severity has an important psychological effect on the patient (2)

Cases of iatrogenic botulism have been reported following the therapeutic or cosmetic use of botulinum toxin containing products where the toxin’s effect extends beyond the area of treatment (2):

• botulism caused by botulinum toxin is rare but can be life threatening:
  • symptoms can take up to four weeks to develop and may typically include difficulty breathing or shortness of breath, difficulty swallowing, talking or slurred speech and muscle weakness
  • in severe cases, patients may require mechanical ventilation and intensive care treatment

The risk of adverse reactions from the spread of toxin or botulism may be increased in patients:

• who have underlying conditions and comorbidities (underlying neurological disorders, or a history of dysphagia or aspiration)
• where high doses of botulinum toxin are used
• where a product is used outside of its licensed indications (off-label) and administered into unapproved sites
• where a counterfeit or unauthorised botulinum toxin containing product is used

In patients presenting with only localised side effects where administration of botulinum antitoxin is not indicated (2):

• it may be necessary to monitor for further progression of symptoms and presentation of systemic neurological symptoms

Key Advice for Healthcare Professionals

• cases of iatrogenic botulism, (botulism caused by a therapeutic or cosmetic procedure) following use of botulinum toxin containing products have been rarely reported
• symptoms of iatrogenic botulism typically occur between 4 and 8 days but can take up to 4 weeks to develop following treatment with botulinum toxin
• risks of botulism may be increased in patients with underlying disorders that may predispose them, the use of high-doses of botulinum toxin, using a product off-label or administering a product into unapproved sites, or in the use of counterfeit or unauthorised products
• the product information for these products is being updated to include a warning of iatrogenic botulism
• advise new and existing patients to be aware of symptoms of botulism including, severe drooping of the upper eye lids difficulty breathing, speaking (slurred speech) and difficulty swallowing. This is a medical emergency and patients should be advised to seek immediate medical help
• if you suspect your patient may have botulism, follow the UK Health Security Agency advice on the clinical management of iatrogenic botulism
• check that the botulinum toxin product is authorised for use and follow the product specific guidance in the product information for administration, dose and indication
• prescribers should ensure that anyone they direct to administer the product, including practitioners who may use it for cosmetic purposes, follow the directions on the prescription and that they are familiar with this Drug Safety Update and the actions to be taken
• report any suspected side effects or complications via the Yellow Card scheme

Reference:

1. Park MY, Ahn KY. Scientific review of the aesthetic uses of botulinum toxin type A. Arch Craniofac Surg. 2021 Feb;22(1):1-10.
2. MHRA Drug Safety Update volume 19, issue 12: July 2026: 1.