Evidence review: safety

Evidence review: safety

The Cochrane review provided limited evidence on the safety of using botulinum toxin type A for chronic anal fissure.

Yiannakopoulou et al. (2012) included data from trials included in its assessment of efficacy and 10 additional trials. It highlighted that adverse events associated with botulinum toxin type A may differ between different indications since they are typically consequences of diffusion of the toxin to adjacent muscles, although systemic effects have been reported when it was used for other indications.

Yiannakopoulou et al. (2012) concluded that, in general, low levels of adverse events were reported in clinical trials and most of them were localised. One of the expected adverse events when botulinum toxin is injected into the internal anal sphincter is temporary incontinence to flatus in approximately 10% of patients, and to liquids and faeces in approximately 5% of patients. This compares with reports of up to 30% of patients having difficulty controlling flatus, 20% soiling and 3–10% having episodes of leakage after surgery (Cross et al. 2008), although other reports (Nelson et al. 2011) suggest lower rates of usually no more than 5% having anal incontinence after surgery in more recent years. Perianal haematoma and perianal thrombosis have also been reported (Yiannakopoulou et al. 2012). Reduced tissue tone surrounding the inferior haemorrhoidal plexus was implicated in the specific cases discussed.

Other possible complications include thrombosis of external haemorrhoids, prolapse of internal haemorrhoids and perianal abscess. The Yiannakopoulou et al. (2012) review also captured 2 reports of long-term incontinence after botulinum injection.

The review highlighted that botulinum toxin type A is contraindicated in cases of hypersensitivity, pregnancy, neurological disease including myasthesia, Lambert Eaton syndrome and amyotrophic lateral sclerosis. Co-administration with aminoglycosides is also contraindicated because of the possibility of enhancement of the action of the toxin.

A specific drug safety update was issued in March 2013 by the Medicines and Healthcare products Regulatory Agency (MHRA) concerning the potential dangers of toxin spread using botulinum toxin type B, mostly through off-label use. In 2007 a specific drug safety update had been issued for all products containing botulinum toxin about the risk of serious adverse reactions caused by distant spread of the toxin. The risk of toxin spread with botulinum toxins is rare but serious and has been reported with all products in this class. The MHRA advises that all patients receiving any product containing botulinum toxin should be warned of the signs and symptoms of toxin spread, such as muscle weakness and breathing difficulties, and advised to seek medical attention immediately if they experience breathing difficulties, choking, or any new or worsening swallowing difficulties, as such side effects may be life-threatening.