Patients choosing intradetrusor onaBoNT-A should be counseled regarding risk of transient urinary retention seen in 6% of patients given 100 U in the FDA qualifying trials and 8% given 200 U in the 6-month Refractory Overactive Bladder: Sacral Neuromodulation vs. Botulinum Toxin Assessment (ROSETTA) trial.⁶,⁷,¹⁶ Despite these low risks of urinary retention, it is recommended that patients learn clean intermittent catheterization (CIC) prior to the procedure to be prepared in case it is needed. Urinalysis is performed on the day of
injection to rule out UTI. To avoid canceling injection on the date scheduled because of symptomatic UTI, it is recommended that the patient submit a urine culture at least 1 week prior to allow time to result and treat with antibiotics. Any anticoagulation must be held prior to the injection to decrease problematic hematuria that could necessitate a trip to the operating room (OR) for fulguration and clot evacuation.

Antibiotics are typically given prior to injection of intradetrusor onaBoNT-A. In the phase 3 RCTs for iOAB evaluating the 100-U dose of onaBoNT-A versus placebo, the incidence of UTIs was reported to be 25.5% in those treated with onaBoNT-A (n = 557) compared to 9.6% in those treated with placebo (n = 548), P < .001.⁶,⁷ In a retrospective study of 284 patients who received either one dose of ceftriaxone intramuscularly (n = 236) or a 3-day course of oral fluoroquinolone starting the day prior to onaBoNT-A administration (n = 48), Houman et al.¹⁷ found that the UTI rate was 20.8% for those receiving the fluoroquinolone versus 36% in the ceftriaxone group, P = .04.

Intradetrusor onaBoNT-A injection can be performed either in the office using local anesthesia or in the OR under sedation. Intravesical instillation of 60 mL of 1% lidocaine for 20 to 30 minutes prior to injection is commonly used for office injection. The onaBoNT-A is injected into the bladder wall using direct cystoscopic visualization. An injection needle (27G) is introduced into the bladder lumen under direct visualization, and the needle is placed between 2 and 4 mm into the bladder wall for multiple injections. Each 100 U of onaBoNT-A is gently mixed with 0.9% injectable saline in a 10-mL syringe. Twenty injections (each 0.5 mL) are placed into the extratrigonal bladder walls.¹⁸ The injections should be limited to the bottom half of the bladder.

After completion of all injections, full visualization of the bladder should be performed to confirm hemostasis at all sites. Bleeding at any injection site can be treated with either pressure for 1 to 2 minutes using the cystoscope tip or with cautery using a Bugbee electrode. Because cautery may be needed in rare cases, it is recommended to use sterile water as the cystoscopic fluid. All patients should follow-up in 2 to 3 weeks after injection to assess efficacy and to check postvoid residual (PVR) volume for urinary retention that may require temporary CIC.

Varying injection techniques and dosages of ona-BoNT-A have been described for the treatment of OAB. We will review the literature supporting current recommendations by the AUA/SUFU for the FDA-approved dosage of 100 U of onaBoNT-A for the treatment of iOAB refractory to first and second line OAB treatments.⁹ The risk of side effects increase with doses more than 100 U, and these include urinary retention and UTI. Temporary retention necessitating CIC was seen in 6% of OAB patients given 100 U (n = 1,105) in the FDA qualifying trials⁶,⁷ and in 8% of the OAB patients given 200 U (n = 192) in the 6-month ROSETTA trial.¹⁶ The risks of UTIs, all uncomplicated with no upper tract involvement, was 25.5% for the OAB patients given 100 U in the FDA qualifying trials⁶,⁷ and 35% for the OAB patients given 200 U in the 6-month ROSETTA trial¹⁶ and 24% during longer follow-up in the 2-year ROSETTA trial.¹⁹

Several RCTs have focused on establishing the dose response by varying doses of botulinum A compared to placebo. Dmochowski et al.²⁰ performed a randomized dose-ranging trial of onaBoNT-A in OAB patients with eight or more episodes of UUI per week, and they demonstrated that onaBoNT-A 100 U maximized symptom improvement while minimizing urinary retention for which CIC was initiated. Fowler et al.²¹ compared different doses of onaBoNT-A to placebo in OAB patients, and they found improvement from baseline in Incontinence Quality of Life (I-QOL) at 36 weeks in groups given more than 100 U, P < .05. Rovner et al.²² compared onaBoNT-A doses for OAB ranging from 50 to 300 U, and after 12 weeks, the number of patients with more than 75% improvement in urgency and UUI episodes (UUIEs) was 6% for patients given 50 U compared to 42% for both 100 and 150 U groups. Denys et at.²³ performed a double-blinded, placebo-controlled, multicenter RCT comparing onaBoNT-A 50 U, 100 U, 150 U, and placebo, and after 5 months, dry rates were 15.8%, 45%, 45.8%, and 7.1%, P < .009. For patients given 50 U, there was no significant symptomatic improvement above placebo at any time point. Likewise, Cohen et al.²⁴ found no difference in urinary frequency or urodynamics measures with either the 100- or 150-U doses after 3 months; however, there was a trend toward improved dry rates in patients receiving 150 U.

For dosages of abobotulinumtoxinA, de Sá Dantas Bezerra et al.²⁵ compared 300 U versus 500 U in a prospective, randomized study of 21 women with OAB, and they found at 12 weeks, there were similar dry rates of 91% and similar increases of 86 mL (300 U) and 71 mL (500 U) in maximum cytometric capacity, P = .27; however, by 24 weeks, 50% of patients given 300 U saw incontinence return compared to 0% given 500 U group. A similar trend in both groups at 24 weeks was seen in the Patient Global Impression of Improvement (PGI-I) scores. Because there was no significant difference in PVR at 4 weeks between 300 U (71.7 mL) and 500 U (96.5 mL) and no difference in UTI rates, these authors concluded that the 500-U dose was superior with a longer duration of effect and no increase in adverse events (AEs).

Various techniques for the delivery of intradetrusor ona-BoNT-A have been studied to evaluate efficacy and AEs. These techniques compare supratrigonal-only versus inclusion of trigonal injections, and they evaluate different depths of injection. Earlier studies, including the FDA qualifying studies, advocated for supratrigonal injection to minimize the potential development of vesicoureteral reflux (VUR) from injections placed too close to the ureteral orifices.⁶,⁷ Kuo²⁶ compared delivering onaBoNT-A 100 U into either only the bladder body (n = 37), 75 U into the bladder body and 25 U into the trigone (n = 35), or 50 U into the bladder base and 50 U into the trigone (n = 33). The study enrolled 105 patients, including 57 women and 48 men, and all patients completed the injection and at least two follow-up visits. Success was defined as moderate or marked improvement in the patient’s perception of bladder condition. Kuo²⁶ found no significant differences between treatment success (72%) or dry rates (also 72%) among the groups at 3 months. Acute urinary retention was 6% overall with no difference between groups (P = .127), but the bladder base and trigone injection group had no retention and no patient with trigone injection developed VUR at 3 months. More recently, Jo et al.²⁷ performed a meta-analysis of eight studies (419 subjects), including the Kuo study, evaluating the effect of intradetrusor onaBoNT-A according to injection site. Compared to trigone sparing techniques, injecting onaBoNT-A into the trigone demonstrated significant symptom score (I-QOL and Overactive Bladder Symptom Score [OABSS]) improvement (P = .04), higher dryness rates (P = .002), and fewer UUIEs (P = .02). When comparing intradetrusor to suburothelial injection, there were no differences in the incidence of VUR, PVR, or UTIs. Jo et al.²⁷ concluded that injecting onaBoNT-A into the trigone was more efficacious that supratrigonal-only injections, and the risks of AEs was similar between techniques. Also, the depth of onaBoNT-A injection did not change either efficacy or safety.