What is the max dose of onabotulinumtoxinA (Botox) in pediatric patients with overactive bladder?

Comment by InpharmD Researcher

Available data on the maximum dose of onabotulinumtoxinA (Botox) in pediatric patients with overactive bladder indicate a wide range of dosing variability, with reported doses up to 1200 U depending on weight, clinical protocols, and injection sites. While 100 U per session appears to be the most commonly used standard dose, higher doses, such as 500 U, have been reported in select studies, often showing increased efficacy without significant adverse events. A standardized defined maximum dose of Botox was not consistently reported across studies.

Background

A 2024 systematic review and meta-analysis evaluated the safety and efficacy of botulinum toxin A (BoNT-A) in children and adolescents with neurogenic lower urinary tract dysfunction (NLUTD) and idiopathic overactive bladder (OAB). A total of 41 studies (N= 1521 patients) were included for analysis. The studies assessed outcomes such as urinary incontinence (UI), urodynamic changes, and adverse events over varying follow-up periods, typically lasting between 2 weeks and 12 months. BoNT-A was primarily administered intradetrusor via cystoscopic injections, with doses typically adjusted by weight, ranging up to 500 IU per session. The most frequently used dose was 100 IU/kg. Quantitative analysis revealed that BoNT-A led to a mean improvement rate of 75.87% in UI episodes and a 51.24% dryness rate within 3–6 months of treatment. Urodynamic parameters also demonstrated statistically significant improvements, including reductions in maximum detrusor pressure and increases in bladder compliance and capacity. Meta-regression indicated that younger age and higher baseline bladder compliance were predictive of improved dryness rates, suggesting that early intervention may enhance therapeutic success. No major adverse effects were reported, with urinary tract infections and mild hematuria being the most common complications. However, there remained a lack of consensus regarding the optimal dose, number, location of injection, or way of administration which depended on trial design and disease etiology. [1]

A 2024 systematic review evaluated the role of intravesical BoNT-A in managing refractory idiopathic OAB in pediatric patients. The review assessed eight studies (N= 202 children aged 4 to 19 years). All children were refractory to conservative treatment such as behavioral therapy, rehabilitation, or anticholinergic medication. The review highlighted considerable heterogeneity in treatment protocols, including variations in BoNT-A type (onabotulinum toxin A or abobotulinum toxin A), doses (ranging from 50 U to 500 U), injection sites, and dilution methods. While most studies involved intradetrusor injections, typically sparing the trigone area, the number of injection points ranged from 14 to 30. The response rate was highly variable, with full-response rates following initial injections reported between 32% and 60%, and repeated injections demonstrating comparable efficacy with no major adverse events. Clinical outcomes revealed significant symptom improvement, with reductions in incontinence episodes, increased bladder compliance, and enhanced quality of life. Adverse effects were rare and typically transient, including urinary tract infections, transient urinary retention, and hematuria. Although the data support the safety and efficacy of BoNT-A as a second-line therapy for idiopathic OAB in children, the review emphasized the need for standardized protocols and further randomized controlled trials to optimize dosing, injection techniques, and long-term outcomes. [2]

A 2021 systematic review evaluated the safety and efficacy of intravesical BoNT-A injections for children with medically refractory neurogenic bladder. A total of 16 studies (N= 455 pediatric patients) were included for analysis. These children, aged less than 18 years, had neurogenic bladder conditions primarily stemming from underlying neurological disorders such as myelomeningocele or spinal cord injuries. Prior to BoNT-A injections, all patients had undergone standard management involving antimuscarinic medications and clean intermittent catheterization (CIC). Dosages of BTX-A injections ranged from 100 to 1200 units, adjusted to weight or specific clinical protocols, and were delivered into the detrusor muscle via 20 to 50 injection sites. Post-injection, 54–100% of patients experienced reduced or resolved urinary incontinence, and vesicoureteral reflux (VUR) improved in 73–100% of cases. Urodynamic parameters consistently demonstrated favorable changes, including reductions in maximum detrusor pressure by up to 50%, increases in bladder capacity (averaging 1.45 to 3.64 times baseline), and marked improvements in bladder compliance. Adverse events were minimal, with mild hematuria and post-injection urinary tract infections reported in a small subset of cases. These findings underscore the safety and therapeutic potential of BoNT-A injections as an effective second-line option for pediatric neurogenic bladder, particularly when conservative medical therapy fails. [3]

Literature Review

A search of the published medical literature revealed 3 studies investigating the researchable question:

what is the max dose of Botox in pediatric patients with overactive bladder

Level of evidence

C - Multiple studies with limitations or conflicting results Read more→

Please see Tables 1-3 for your response.

Intradetrusor Onabotulinum-A Toxin Injections in Children with Therapy-resistant Idiopathic Detrusor Overactivity. A Retrospective Study
Design	Retrospective study N= 257
Objective	To determine the effectiveness and safety of intradetrusor onabotulinum-A toxin (BoNT-A) injections in children with non-neurogenic detrusor overactivity resistant to conservative therapy
Study Groups	All patients (n= 257)
Inclusion Criteria	Children aged ≤ 18 y/o; therapy-resistant non-neurogenic detrusor overactivity proven by urodynamics; failure of first-line treatments (including urotherapy, anticholinergics, and transcutaneous electrical nerve stimulation [TENS])
Exclusion Criteria	Age > 18 years; neurogenic bladder or dysfunctional voiding; abnormalities on MRI (e.g., tethered cord, spinal lipoma); history of malignancy
Methods	Initial treatment for all patients included urotherapy, oral anticholinergics (e.g., oxybutynin, solifenacin, propiverine, fesoterodine), and TENS. Urotherapy combined behavioral and lifestyle modifications, constipation management, and symptom tracking using bladder diaries or frequency–volume charts. Additionally, 31.9% of patients attended a 2-week voiding school program involving dietary and hydration corrections, biofeedback training, uroflowmetry, and alarm systems. Patients were classified as therapy-resistant if they failed first-line treatments, including urotherapy, anticholinergics, and TENS. Invasive urodynamics confirmed detrusor overactivity in 96.9% of the cohort. Treatment involved intradetrusor injection of 100 U BoNT-A, diluted in 10 mL saline, administered under general anesthesia using cystoscopic guidance. Injections were delivered at 10 to 20 sites, sparing the bladder dome, ventral bladder wall, and trigone to avoid complications. Prophylactic antibiotics were given to all patients and post-procedure, patients were discharged after successful spontaneous voiding.
Duration	Enrollment: May 2003 to August 2017 Follow-up: 11 months (interquartile range [IQR] 3.5 to 23.5 months)
Outcome Measures	Reduction in daytime incontinence episodes/week; reduction in enuresis episodes/week; improvement in bladder capacity (BC) (as a percentage of expected capacity for age)
Baseline Characteristics		All patients (N= 257)
	Age, years (IQR)	8 (7 to 10)
	Female	102 (39.6%)
	Clinical findings Urgency ID EN ID and EN Decreased bladder capacity for age	251 (97.7%) 40 (16.7%) 43 (16.7%) 168 (65.4%) 200 (77.8%)
	Post void residual Number of patients Median, ml (IQR)	14/257 (5.4%) 30 (14.5 to 32.3)
	Invasive urodynamics Detrusor overactivity	249 (96.9%) 100%
	Treatment duration before injection, months (IQR)	40 (25.8 to 59.3)
	Injection series 1 2 3 4	155 (60.3%) 69 (26.8%) 20 (7.8%) 13 (4.9%)
	Abbreviations: ID, daytime incontinence; EN, enuresis
Results	Response rates in patients with daytime incontinence or enuresis	Missing	CR	PR	FoT
	EN (n= 43)	3	20 (50%)	5 (12.5%)	15 (37.5%)
	ID (n= 40)	5	16 (45.7%)	6 (17.1%)	13 (37.1%)
	Response rates in patients with both daytime incontinence and enuresis
	ID (n= 168)	21	78 (53.1%)	35 (23.8%)	34 (23.1%)
	EN (n= 168)	21	31 (21.1%)	6 (4.1%)	110 (74.8%)
	ID and EN (n= 147)		25 (17%)
	Difference in BC (%) before and after BoNT-A injection	BC before	BC after	MD	P-value
	First BoNT-A injection (n= 159)	59.9 ± 22.6	83.1 ± 27.4	23.1	<0.0001
	Second BoNT-A injection (n= 40)	67.7 ± 21.8	99.3 ± 41.7	31.6	<0.0001
	Third BoNT-A injection (n= 14)	77.4 ± 18.6	94.1 ± 28.7	16.8	0.008
	Abbreviations: CR, complete response; PR, partial response; FoT, failure of treatment
Adverse Events	Common Adverse Events: Urinary tract infections (6.6%)
	Serious Adverse Events: Urinary retention requiring catheterization (0.4%); vesicoureteral reflux (1.2%)
	Percentage that Discontinued due to Adverse Events: Not disclosed.
Study Author Conclusions	BoNT-A injection is a potentially effective adjuvant therapy in the treatment of children with therapy-resistant overactive bladder (OAB). Bladder capacity increases significantly after the first, second, and third injections. A better effect on daytime incontinence than on enuresis was seen. Prospective randomized trials with standardization of conservative treatment and symptoms questionnaires are necessary to confirm the beneficial effect of BoNT-A injections on BC and incontinence.
InpharmD Researcher Critique	The study provides insight into the safety and efficacy of BoNT-A in a challenging pediatric population, supported by significant clinical improvements. However, its retrospective design and lack of standardized pre- and post-treatment protocols may limit the robustness of its findings.

References:

Ringoir A, Dhondt B, De Bleser E, et al. Intradetrusor onabotulinum-a toxin injections in children with therapy-resistant idiopathic detrusor overactivity. A retrospective study. J Pediatr Urol. 2020;16(2):181.e1-181.e8. doi:10.1016/j.jpurol.2019.12.013

Non-invasive evaluation of botulinum-A toxin treatment efficacy in children with refractory overactive bladder
Design	Retrospective observational study N= 31
Objective	To evaluate the efficacy and safety of intravesical onabotulinum toxin A (onaBoNTA) injections for the treatment of children diagnosed with refractory overactive bladder (OAB) by using non-invasive methods
Study Groups	All subjects (N = 31)
Inclusion Criteria	Patients with persistent urgency and urinary incontinence, refractory to 6 months of medical and behavioral (urotherapy) therapy
Exclusion Criteria	Patients with neurogenic bladder or dysfunctional voiding, patients whose constipation was not treated, and those with incomplete data in their files
Methods	Medical records of pediatric patients receiving intravesical botulinum toxin A (onaBoNTA) injections from 2008 to 2015 were retrospectively analyzed. Data collected included medical history, pre- and postoperative symptom scores (DVISS), voiding diaries, physical exams, urine analysis, renal/bladder ultrasonography, postoperative complications, and residual urine volume. Botulinum toxin (10 U/kg, max 200 U) was administered under general anesthesia with antibiotic prophylaxis. Therapy response was categorized as no response (<50% improvement), partial (50–99%), or full (100%). Patients with incomplete responses received a second injection at the same dose and technique.
Duration	2008 to 2015
Outcome Measures	Therapy response
Baseline Characteristics		All subjects (N= 31)
	Age, years	10.2 (range 7-15)
	Female	22 (70.9%)
	Assessment of bladder diaries Ratio of FBC to EB Voiding frequency/day Urgency/day Urge incontinence attack/day	67.3% 9 4 2
	DVISS	8 (4-15)
	DVISS, Dysfunctional Voiding and Incontinence Symptom Score; EBC, estimated bladder capacity; FBC, functional bladder capacity
Results	Endpoint	All subjects (N= 31)
	Six-months after the first injection Complete response Partial response No response	10 (32.2%) 15 (48.4%) 6 (19.4%)
	Patients without complete response after the first injection (n = 21) Received second injection 6 months after the first injection Complete response Partial response No response	21 (100% 9 (42.9%) 9 (42.9%) 3 (14.3%)
	One year after the first injection Complete response Partial response No response	19 (61.3%) 9 (29%) 3 (9.7%)
Adverse Events	Not disclosed
Study Author Conclusions	Based on our results, onaBoNTA therapy is an effective and reliable second-line off-label therapy in the management of patients with non-neurogenic OAB that is refractory to medical therapy. Asking the patients/guardians to fill out a standardized questionnaire form before and after the therapy enables easy and non-invasive assessment of the response to the therapy
InpharmD Researcher Critique	The study has several limitations, including its retrospective design and a relatively small sample size. The short follow-up period also restricts the ability to assess long-term outcomes.

References:

Uçar M, Akgül AK, Parlak A, Yücel C, Kılıç N, Balkan E. Non-invasive evaluation of botulinum-A toxin treatment efficacy in children with refractory overactive bladder. Int Urol Nephrol. 2018;50(8):1367-1373. doi:10.1007/s11255-018-1926-6

Results of a study examining the use of onabotulinumtoxinA in pediatric patients with overactive bladder
Design	Double-blind, parallel-group, multiple-dose study N= 55
Objective	To investigate the efficacy and safety of onabotulinumtoxinA (OnabotA) treatment of overactive bladder (OAB) in children aged 12 to 17 years who were not adequately managed with anticholinergics
Study Groups	OnabotA 25U (n= 18) OnabotA 50U (n= 17) OnabotA 100U (n= 20)
Inclusion Criteria	Male or female patients aged 12-17 years, had OAB symptoms of frequency and urgency with UI for 6 months and were not adequately managed with 1 anticholinergic agent for OAB, recorded 2 episodes of daytime UI along with urinary frequency (8 micturitions per day) in the 2-day bladder diary during screening, were willing/able to use clean intermittent catheterization (CIC) if necessary, agreed to a minimum fluid intake of 1500 mL/m2 of body surface area (BSA) per day (3000 mL/m2 of BSA per day).
Exclusion Criteria	Previous or current malignancy, symptoms of OAB due to any known neurologic reason, history of 2 UTIs treated with antibiotics within 6 months of randomization or prophylactic antibiotic use to prevent UTIs, use of CIC or an indwelling catheter to manage OAB, postvoid residual (PVR) urine volume of >40 mL at screening, daytime total volume of urine voided >3000 mL in 2-day bladder diary prior to randomization.
Methods	OnabotA was dosed at either 25U, 50U, or 100U (≤ 6 U/kg) and was injected at 20 separate 0.5-mL injections into the detrusor muscle, avoiding the trigone, via cystoscopy. Scheduled clinic visits were at weeks 2, 6, and 12 post-treatment, then alternating telephone and clinic visits every 6 weeks. Patients could request 1 retreatment starting at week 12 if they had ≥ 1 daytime urgency UI episode, PVR <200 mL, and no serious treatment-related adverse events. Patients were discontinued if the investigator requested a dose increase from the 100U dose twice.
Duration	12 weeks
Outcome Measures	Primary: Change in daytime urinary incontinence (UI) episodes from baseline to week 12 Secondary: Proportion of patients with 0 nighttime incontinence episodes at week 12, mean volume voided per micturition, positive treatment response (greatly improved or improved)
Baseline Characteristics		OnabotA 25U (n= 18)	OnabotA 50U (n= 17)	OnabotA 100U (n= 20)
	Median age, years	13	14	14
	Gender Female Male	88.9% 11.1%	100% 0	70% 30%
	Race White Asian Other Not reported Unknown	66.7% 0 5.6% 11.1% 16.7%	70.6% 5.9% 5.9% 5.9% 11.8%	85.0% 0 5.0% 5.0% 5.0%
	Weight, kg	61.4	60	57.5
	Duration of OAB, years	3.2	3.7	2.9
Results	Endpoint	OnabotA 25U (n= 18)	OnabotA 50U (n= 17)	OnabotA 100U (n= 20)
	Daily frequency of daytime micturition episodes Baseline (standard deviation [SD]) Change from baseline at week 12 (95% CI) Difference vs OnabotA 25U at week 12 (95% CI) p-Value vs onabotA 25U p-Value within group	11.2 (4.2) -1.8 (-3.9 to 0.2) -- -- --	8.5 (2.0) 0.3 (-1.7 to 2.4) 2.2 (-0.8 to 5.0) 0.15 0.76	8.1 (2.5) -1.0 (-3.0 to 1.0) 0.82 (-2.1 to 3.7) 0.57 0.30
	Proportion of patients with 0 nighttime incontinence episodes at week 12	9 (50%)	13 (76.5%)	10 (50%)
	Change in mean volume voided per micturition at 12 weeks. mL (95% CI)	-9.2 (-41.2 to 22.8)	24.9 (-9.3 to 59.2)	26.2 (-5.8 to 58.1)
	Positive treatment response (greatly improved or improved) at week 12	9 (52.9%)	12 (70.6%)	13 (68.4%)
Adverse Events	Urinary retention in 1 patient after treatment with 100U during cycle 2 occurring 167 days after the last treatment Residual urine volume in 1 patient on day 29 of cycle 4
Study Author Conclusions	OnabotulinumtoxinA injections were well tolerated in children with OAB at all doses studied. Although the primary endpoint was not met, the significantly greater treatment response rate observed with onabotulinumtoxinA 100U versus 25U suggests additional benefit of the higher dose, without additional safety concerns.
InpharmD Researcher Critique	The study was prematurely terminated due to enrollment challenges, resulting in a smaller sample size of 56 patients instead of the planned 108. Furthermore, the study lacked of a placebo arm due to ethical concerns in children, and the treatment benefits observed in the low-dose comparator arm made it difficult to draw definitive conclusions about efficacy differences between the treatment groups.

References:

Hoebeke P, Hittelman A, Jenkins B, Geib T, Titanji W, Bogaert G. Results of a study examining the use of onabotulinumtoxinA in pediatric patients with overactive bladder. J Pediatr Urol. 2024;20(4):600.e1-600.e8. doi:10.1016/j.jpurol.2024.04.019