BOTOX® safety profile in clinical trials
In BOTOX® clinical studies:
- 93.5% of patients did NOT initiate CIC2
- The vast majority of patients (99.8%) did not develop a complete inability to void6
– Based on a post hoc, pooled analysis of 2 pivotal studies
*Adverse reactions reported by ≥ 2% of BOTOX® treated patients and more often than in placebo-treated patients within the first 12 weeks.2 † Elevated PVR urine volume not requiring catheterization. Catheterization was required for PVR ≥ 350 mL regardless of symptoms, and for PVR ≥ 200 mL to < 350 mL with symptoms (eg, voiding difficulty).2 ‡ Post-void residual. § Clean intermittent catheterization.
BOTOX® for injection is indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency, in adults who have an inadequate response to or are intolerant of an anticholinergic medication.
BOTOX® is indicated for the treatment of urinary incontinence due to detrusor overactivity associated with a neurologic condition (eg, SCI, MS) in adults who have an inadequate response to or are intolerant of an anticholinergic medication.
Postmarketing reports indicate that the effects of BOTOX® and all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. These may include asthenia, generalized muscle weakness, diplopia, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence, and breathing difficulties. These symptoms have been reported hours to weeks after injection. Swallowing and breathing difficulties can be life threatening, and there have been reports of death. The risk of symptoms is probably greatest in children treated for spasticity, but symptoms can also occur in adults treated for spasticity and other conditions, particularly in those patients who have an underlying condition that would predispose them to these symptoms. In unapproved uses and in approved indications, cases of spread of effect have been reported at doses comparable to those used to treat Cervical Dystonia and spasticity and at lower doses.
BOTOX® is contraindicated in the presence of infection at the proposed injection site(s) and in patients who are hypersensitive to any botulinum toxin product or to any of the components in the formulation.
Spread of Toxin Effect
See Boxed Warning.
The potency Units of BOTOX® are specific to the preparation and assay method utilized. They are not interchangeable with other preparations of botulinum toxin products and, therefore, Units of biological activity of BOTOX® cannot be compared to nor converted into Units of any other botulinum toxin products assessed with any other specific assay method.
Serious adverse reactions, including excessive weakness, dysphagia, and aspiration pneumonia, with some adverse reactions associated with fatal outcomes, have been reported in patients who received BOTOX® injections for unapproved uses. In these cases, the adverse reactions were not necessarily related to distant spread of toxin, but may have resulted from the administration of BOTOX® to the site of injection and/or adjacent structures. In several of the cases, patients had pre-existing dysphagia or other significant disabilities. There is insufficient information to identify factors associated with an increased risk for adverse reactions associated with the unapproved uses of BOTOX®. The safety and effectiveness of BOTOX® for unapproved uses have not been established.
Serious and/or immediate hypersensitivity reactions have been reported. These reactions include anaphylaxis, serum sickness, urticaria, soft-tissue edema, and dyspnea. If such a reaction occurs, further injection of BOTOX® should be discontinued and appropriate medical therapy immediately instituted. One fatal case of anaphylaxis has been reported in which lidocaine was used as the diluent, and consequently the causal agent cannot be reliably determined.
Individuals with peripheral motor neuropathic diseases, amyotrophic lateral sclerosis (ALS), or neuromuscular junction disorders (eg, myasthenia gravis or Lambert-Eaton syndrome) should be monitored when given botulinum toxin. Patients with known or unrecognized neuromuscular disorders or neuromuscular junction disorders may be at increased risk of clinically significant effects including generalized muscle weakness, diplopia, ptosis, dysphonia, dysarthria, severe dysphagia, and respiratory compromise from therapeutic doses of BOTOX® (see Warnings and Precautions).
Treatment with BOTOX® and other botulinum toxin products can result in swallowing or breathing difficulties. Patients with pre-existing swallowing or breathing difficulties may be more susceptible to these complications. In most cases, this is a consequence of weakening of muscles in the area of injection that are involved in breathing or oropharyngeal muscles that control swallowing or breathing (see Boxed Warning).
Patients with compromised respiratory status treated with BOTOX® for detrusor overactivity associated with a neurologic condition should be monitored closely.
Autonomic dysreflexia associated with intradetrusor injections of BOTOX® could occur in patients treated for detrusor overactivity associated with a neurologic condition and may require prompt medical therapy. In clinical trials, the incidence of autonomic dysreflexia was greater in patients treated with BOTOX® 200 Units compared with placebo (1.5% vs 0.4%, respectively).
BOTOX® increases the incidence of urinary tract infection. Clinical trials for overactive bladder excluded patients with more than 2 UTIs in the past 6 months and those taking antibiotics chronically due to recurrent UTIs. Use of BOTOX® for the treatment of overactive bladder in such patients and in patients with multiple recurrent UTIs during treatment should only be considered when the benefit is likely to outweigh the potential risk.
Due to the risk of urinary retention, treat only patients who are willing and able to initiate catheterization post treatment, if required, for urinary retention.
In clinical trials, 6.5% of patients (36/552) initiated clean intermittent catheterization for urinary retention following treatment with BOTOX® 100 Units as compared to 0.4% of patients (2/542) treated with placebo. The median duration of catheterization for patients treated with BOTOX® 100 Units was 63 days (minimum 1 day to maximum 214 days) as compared to a median duration of 11 days (minimum 3 days to maximum 18 days) for patients receiving placebo.
In clinical trials, 30.6% of patients (33/108) who were not using clean intermittent catheterization (CIC) prior to injection, required catheterization for urinary retention following treatment with BOTOX® 200 Units as compared to 6.7% of patients (7/104) treated with placebo. The median duration of postinjection catheterization for these patients treated with BOTOX® 200 Units (n = 33) was 289 days (minimum 1 day to maximum 530 days) as compared to a median duration of 358 days (minimum 2 days to maximum 379 days) for patients receiving placebo (n = 7).
This product contains albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases and variant Creutzfeldt-Jakob disease (vCJD). There is a theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD), but if that risk actually exists, the risk of transmission would also be considered extremely remote. No cases of transmission of viral diseases, CJD, or vCJD have ever been identified for licensed albumin or albumin contained in other licensed products.
Adverse reactions to BOTOX® for injection are discussed in greater detail in the following sections: Boxed Warning, Contraindications, and Warnings and Precautions.
The most frequently reported adverse reactions for overactive bladder occurring within 12 weeks of injection include urinary tract infection (BOTOX® 18%, placebo 6%), dysuria (BOTOX® 9%, placebo 7%), urinary retention (BOTOX® 6%, placebo 0%), bacteriuria (BOTOX® 4%, placebo 2%), and residual urine volume (BOTOX® 3%, placebo 0%).
The most frequently reported adverse reactions within 12 weeks of BOTOX® injection for detrusor overactivity associated with a neurologic condition include urinary tract infection (BOTOX® 24%, placebo 17%), urinary retention (BOTOX® 17%, placebo 3%), and hematuria (BOTOX® 4%, placebo 3%).
Adverse reactions that have been identified during postapproval use of BOTOX® are discussed in greater detail in Postmarketing Experience (Section 6.3 of the Prescribing Information).
Co-administration of BOTOX® and other agents interfering with neuromuscular transmission (eg, aminoglycosides, curare-like compounds) should only be performed with caution as the effect of the toxin may be potentiated. Use of anticholinergic drugs after administration of BOTOX® may potentiate systemic anticholinergic effects. The effect of administering different botulinum neurotoxin products at the same time or within several months of each other is unknown. Excessive neuromuscular weakness may be exacerbated by administration of another botulinum toxin prior to the resolution of the effects of a previously administered botulinum toxin. Excessive weakness may also be exaggerated by administration of a muscle relaxant before or after administration of BOTOX®.
Postmarketing reports indicate that the effects of BOTOX® and all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. These may include asthenia, generalized muscle weakness, diplopia, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence, and breathing difficulties. These symptoms have been reported hours to weeks after injection. Swallowing and breathing difficulties can be life threatening, and there have been reports of