The American College of

Obstetricians and Gynecologists

WOMEN’S HEALTH CARE PHYSICIANS

COMMITTEE OPINION
Number 604 • June 2014
(Reaffirmed 2017)
Committee on Gynecologic Practice
American Urogynecologic Society
This document reflects emerging clinical and scientific advances as of the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed.

OnabotulinumtoxinA and the Bladder

ABSTRACT: In January 2013, the U.S. Food and Drug Administration approved the use of onabotulinum-
toxinA (also known as Botox A) for the treatment of overactive bladder, thus providing another treatment option
for women. Symptoms of overactive bladder have been shown to significantly improve after onabotulinumtoxinA
injections compared with no intervention, placebo, pharmacological treatments, and bladder instillation technique.
Before considering medical or surgical treatment, all patients in whom overactive bladder is diagnosed should
receive instruction in behavioral techniques (eg, bladder retraining drills and timed voids), fluid management, or
pelvic muscle exercises with or without physical therapy. Intradetrusor onabotulinumtoxinA may be a second-line
treatment option for overactive bladder in appropriate patients, and consideration of its use requires shared deci-
sion making between the patient and health care provider. Patients who are candidates for onabotulinumtoxinA
injections into the bladder should be counseled about its risks and possible postprocedure adverse events,
including the risk of postprocedure urinary retention, urinary tract infections, hematuria, pain, and transient body
weakness. Health care providers who perform onabotulinumtoxinA injections must have appropriate training and
experience in treating women with pelvic floor disorders, operative cystoscopy privileges, and the ability to diag-
nose and manage any adverse outcomes after onabotulinumtoxinA injections into the bladder.

The U.S. Food and Drug Administration (FDA) approved Botulinum toxin, a potent neurotoxin derived from
onabotulinumtoxinA (also known as Botox A) for cos- the anaerobic bacterium Clostridium botulinum, acts
metic use in 1991. It has since been FDA-approved for primarily as a muscle paralytic by inhibiting the presyn-
treatment of blepharospasm, strabismus, cervical neck aptic release of acetylcholine from motor neurons at the
dystonia, hyperhidrosis, chronic migraine, and upper neuromuscular junction. Botulinum toxin also has effects
limb spasticity. In August 2011, onabotulinumtoxinA on the afferent side of the nervous system by decreasing
was approved for the treatment of neurogenic bladder; in the sensory response of the C afferent fibers. There are
January 2013, it was approved for treatment of overactive several subtypes of botulinum toxin, but the most com-
bladder. Overactive bladder, a term initially introduced monly used is subtype A. OnabotulinumtoxinA is admin-
by the pharmaceutical industry, is defined as urinary istered by cystoscopic injection of multiple aliquots into
urgency, typically accompanied by frequency and noc- the detrusor muscle. The FDA-approved dosage for the
turia, with and without urge urinary incontinence in treatment of neurogenic bladder is 200 units; the FDA-
the absence of urinary tract infection or other obvious approved dose for overactive bladder is 100 units.
pathology (1). The term overactive bladder includes
the previously defined term of “detrusor overactivity” Efficacy
(idiopathic) (2). This joint Committee Opinion of the An extensive Cochrane review (3) has summarized the
American College of Obstetricians and Gynecologists and literature for the use of botulinum toxin for overactive
the American Urogynecologic Society will focus on the bladder. Symptoms of overactive bladder have been
use of onabotulinumtoxinA for the treatment of overac- shown to significantly improve after botulinum toxin
tive bladder. injections even at 12 months (P<.001) compared with
no intervention, placebo, pharmacological treatments, cystoscope with injection needle. Injections are spread out
and bladder instillation technique. This review also sum- over different rows to equally cover the bladder dome and
marized results of different types, doses, and injection posterior base, sparing the trigone and ureteral orifices
techniques of botulinum toxin. (see Fig. 1).
A multi-institutional, randomized, double-blind, The patient should be observed until a spontaneous
placebo controlled trial compared 200 units of onabotu- void occurs. If the patient is unable to void or demonstrates
linumtoxinA with placebo for neurologically normal inadequate voiding, she should be instructed on self-
women who were refractory to two first-line treatments catheterization. See “Postprocedure Recommendations”
(4). The trial demonstrated that 60% of the women who for additional information.
received onabotulinumtoxinA had a clinical response
based on the Patient Global Impression of Improvement Candidates for OnabotulinumtoxinA
index. Even though this study was halted before comple- Bladder Injections
tion because of concerns with elevated postvoid residual Before considering medical or surgical treatment, all
volumes, onabotulinumtoxinA revealed a statistically patients in whom overactive bladder is diagnosed should
significant improvement over placebo. receive instruction in behavioral techniques (eg, bladder
The Anticholinergic vs OnabotulinumtoxinA Com- retraining drills and timed voids), fluid management, or
parison study was a multicenter randomized trial that pelvic muscle exercises with or without physical therapy.
compared the effectiveness of 6 months of daily anticho- A recent randomized controlled trial indicated that ona-
linergic therapy with a single intradetrusor injection of botulinumtoxinA may be considered a second-line treat-
100 units of onabotulinumtoxinA in patients with over- ment (5). Shared decision making between the patient
active bladder symptoms (5). The study included partic- and health care provider should include a discussion
ipants who had never taken anticholinergic medications about where onabotulinumtoxinA injections ultimately
and those who had taken two or fewer prior anticholin- fit in the treatment algorithm depending upon symptom
ergic medications. Results demonstrated that anticholin- severity, bother, presence of other co-morbidities, and
ergics had similar rates of improvement in symptoms of risk–benefit ratio for the patient.
overactive bladder compared with onabotulinumtoxinA Contraindications to onabotulinumtoxinA usage
injections. However, patients who underwent onabotu- ascertained from the medical history include a known
linumtoxinA injections had significantly higher cure hypersensitivity to onabotulinumtoxinA, dysphagia, pre-
rates compared with patients who received anticholiner- existing neuromuscular disorders (myasthenia gravis), and
gic medication. Risk of voiding dysfunction that required compromised respiratory status. OnabotulinumtoxinA is
catheterization and urinary tract infection in women who considered an FDA Pregnancy Category C drug, so there
received onabotulinumtoxinA injection was 5% and 33%, are no adequate and well-controlled studies in pregnant
respectively.
Evaluation
The diagnosis of overactive bladder should be confirmed
by appropriate evaluation. (See Practice Bulletin No. 63
Urinary Incontinence in Women, for information on
eval-uation of urinary incontinence [2].) A differential
diagnosis for overactive bladder may include other disor-
ders such as recurrent urinary tract infections, interstitial
cystitis or painful bladder syndrome, hematuria, and pel-
vic organ prolapse.
Technique of Injection
The technique of mixing the onabotulinumtoxinA and
how to inject it can be found on the package insert (6).
OnabotulinumtoxinA injection is most often performed
as a cystoscopic office procedure under local anesthesia;
however, in certain circumstances, such as patient dis-
comfort or lack of office-based equipment, the injection Fig. 1. Pattern for intradetrusor onabotulinumtoxinA
may be performed in an operating room as an outpatient injections for the treatment of overactive bladder or
procedure. detrusor overactivity associated with a neurologic con-
When performed in an office setting, a local anes- dition. (Reprinted from Allergan I. Botox: highlights of
thetic is instilled into the bladder 30 minutes before prescribing information. Irvine (CA): Allergan; 2013.
injection. Cystoscopy may be performed using either a Available at: http://www.allergan.com/assets/pdf/botox_
30-degree lens or with an injection cystoscope or flexible pi.pdf. Retrieved December 18, 2013.) ^

2 Committee Opinion No. 604

women. Caution should be used for women who are Summary and Recommendations
breastfeeding. The January 2013 FDA approval of onabotulinumtoxinA
Patient Counseling for the treatment of overactive bladder provides another
treatment option for women. Where onabotulinum-
Patients who are candidates for onabotulinumtoxinA toxinA bladder injections fit into a health care provider’s
injections into the bladder should be counseled about its treatment algorithm is dependent on an assessment of
risks and possible postprocedure adverse events, includ- each patient’s symptom severity and bother, the effect
ing the risk of postprocedure urinary retention, urinary of incontinence on daily activities, previous treatment
tract infections, hematuria, pain, and transient body history, an assessment of the risk–benefit ratio for the
weakness. Patients who are considering onabotulinum- patient, and the health care provider’s capacity to manage
toxinA injections should be counseled about the risk of postprocedure adverse events. Based on available data and
postprocedure urinary retention or incomplete blad- expert opinion, the American College of Obstetricians
der emptying that may require clean intermittent self- and Gynecologists and the American Urogynecologic
catheterization or catheter placement (5). Patients also Society make the following recommendations:
should be counseled that the effect of onabotulinum- • The diagnosis of overactive bladder should be con-
toxinA is transient and can wear off in 6–15 months; firmed by appropriate evaluation.
reinjections may be needed for continued effectiveness.
The manufacturing label states that patients should be • Intradetrusor onabotulinumtoxinA may be a second-
considered for reinjection when the clinical effect of the line treatment option for overactive bladder in
previous injection has diminished, but no sooner than appropriate patients, and consideration of its use
12 weeks from the prior bladder injection (6). requires shared decision making between the patient
and health care provider. Patients should be coun-
Postprocedure Recommendations seled about risks and possible postprocedure adverse
events of onabotulinumtoxinA injections, including
There are currently no evidence-based recommendations urinary retention, incomplete bladder emptying, and
on when to follow up with patients who have received urinary tract infections.
onabotulinumtoxinA injections. Based upon expert opin-
ion, patients should be contacted 3–7 days postprocedure • Health care providers who perform onabotulinum-
to assess the effectiveness of the injection and assess blad- toxinA injections as a treatment option must have
der emptying. If symptoms cannot be assessed over the appropriate training and experience in treating
women with pelvic floor disorders, operative cystos-
telephone, patients should be seen in the office. Because
copy privileges, and the ability to diagnose and man-
incomplete bladder emptying can occur after the ona-
age any adverse outcomes after onabotulinumtoxinA
botulinumtoxinA injection, and some patients may report
injections into the bladder.
minimal voiding, many experts recommend an in-office
assessment of postvoid residual urine volume by cath- References
eterization or bladder ultrasonography postprocedure or 1. Haylen BT, de Ridder D, Freeman RM, Swift SE, Berghmans
when an assessment of bladder emptying is indicated. B, Lee J, et al. An International Urogynecological Asso-
Clean intermittent self-catheterization may be recom- ciation (IUGA)/International Continence Society (ICS)
mended for postvoid residual volumes greater than joint report on the terminology for female pelvic floor
300 mL or greater than 150 mL in the presence of bother- dysfunction. Int Urogynecol J 2010;21:5–26. [PubMed] ^
some retention symptoms (5). For those patients sent 2. Urinary incontinence in women. Practice Bulletin No.
home who require clean intermittent self-catheterization, 63. American College of Obstetricians and Gynecologists.
a clear follow-up plan should be outlined, including how Obstet Gynecol 2005;105:1533–45. [PubMed] [Obstetrics
often to use the catheter and at what volumes catheteriza- & Gynecology] ^
tion should be continued or discontinued. Urinalysis and 3. Duthie JB, Vincent M, Herbison GP, Wilson DI, Wilson D.
urine culture also may be indicated. Botulinum toxin injections for adults with overactive blad-
der syndrome. Cochrane Database of Systematic Reviews
Clinician Training and Experience 2011, Issue 12. Art. No.: CD005493. DOI: 10.1002/14651858.
CD005493.pub3. [PubMed] [Full Text] ^
Health care providers who perform onabotulinumtoxinA
4. Brubaker L, Richter HE, Visco A, Mahajan S, Nygaard I,
injections must have appropriate training and experience Braun TM, et al. Refractory idiopathic urge urinary incon-
in treating women with pelvic floor disorders, operative tinence and botulinum A injection. Pelvic Floor Disorders
cystoscopy privileges, and the ability to diagnose and Network. J Urol 2008;180:217–22. [PubMed] [Full Text] ^
manage any adverse outcomes after onabotulinumtoxinA 5. Visco AG, Brubaker L, Richter HE, Nygaard I, Paraiso MF,
injections into the bladder. For example, subspecialists in Menefee SA, et al. Anticholinergic therapy vs. onabotu-
female pelvic medicine and reconstructive surgery and linumtoxina for urgency urinary incontinence. Pelvic
urologists are qualified to inject onabotulinumtoxinA for Floor Disorders Network. N Engl J Med 2012;367:1803–13.
overactive bladder. [PubMed] [Full Text] ^

Committee Opinion No. 604 3

 6. Allergan I. Botox: highlights of prescribing information. Also published in Female Pelvic Medicine & Reconstructive Surgery
Irvine (CA): Allergan; 2013. Available at: http://www.aller
gan.com/assets/pdf/botox_pi.pdf. Retrieved December 18, Copyright June 2014 by the American College of Obstetricians and
Gynecologists, 409 12th Street, SW, PO Box 96920, Washington, DC
2013. ^ 20090-6920. All rights reserved.
ISSN 1074-861X
OnabotulinumtoxinA and the bladder. Committee Opinion No. 604.
The American College of Obstetricians and Gynecologists. Obstet
Gynecol 2014;123:1408–11.

4 Committee Opinion No. 604