Title:
Incidence of adverse events after high doses of onabotulinumtoxinA for multiple indications.

Abstract:
To determine the occurrence of all treatment-related adverse events (AEs), especially life-threatening AEs, after the injection of a cumulative dose of >360 units of onabotulinumtoxinA for multiple indications (neurogenic detrusor overactivity, lower limb spasticity, and so forth) within a 3-month interval.
This is a retrospective cohort study of patients who received >360 units of onabotulinumtoxinA within a 3-month interval, with at least 1 urologic indication for injection, between January 1, 2002 and January 1, 2013. The rate of treatment-related AE up to 8 days after injection and life-threatening AE up to 90 days after injection was compared between the injection sessions below and exceeding the maximum dosage recommendations.
Thirteen patients met the study criteria. Eleven were female patients and had a diagnosis of multiple sclerosis. Sixty-five injection sessions involved >360 units of onabotulinumtoxinA administered within a 90-day interval. Median interval between injections was 54 days (interquartile range [IQR], 30-71 days) and median dose administered was 800 units (IQR, 600-1000 units). Seventy injection sessions involved <360 units of onabotulinumtoxinA administered >90 days after prior injection. Median interval between these injections was 113 days (IQR, 97-158 days) and median dose administered was 200 units (IQR, 100-300 units). The maximum cumulative dosage injected was 1900 units (1500 units for lower extremities and 400 units for bladder). This patient did not experience any AE. There was a total of 6 AEs (general and/or extremity weakness or leg pain) that occurred in 4 patients, of a total of 183 injection sessions. These AEs all eventually resolved. There were no life-threatening AEs in either group.
This is the first report of patients receiving >360 cumulative units of onabotulinumtoxinA within a 3-month interval for multiple indications. There were no life-threatening AEs. This study provides preliminary data on administration of high doses of onabotulinumtoxinA for multiple indications.