Onabotulinumtoxina (2 brand names, 1 dosage form, 1 route)
Available dosage forms: VIAL.
Routes of administration: SINGLE-USE.
Brand Names
- BOTOX
- BOTOX COSMETIC
Boxed Warning
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 the se 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 an d spasticity and at lower doses [ see Warnings and Precautions ( 5.1 )] .
Contraindications
BOTOX is contraindicated: In patients who are hypersensitive to any botulinum toxin product or to any of the components in the formulation [see Warnings and Precautions ( 5.4 )]. In the presence of infection at the proposed injection site(s). For intradetrusor injection in patients with a urinary tract infection; or in patients with urinary retention or post-void residual (PVR) urine volume >200 mL who are not routinely performing clean intermittent self-catheterization (CIC) [see Warnings and Precautions ( 5.12 , 5.13 )].
Adverse Reactions
The following adverse reactions to BOTOX (onabotulinumtoxinA) for injection are discussed in greater detail in other sections of the labeling: Spread of Toxin Effects [see Warnings and Precautions ( 5.1 )] Serious Adverse Reactions with Unapproved Use [see Warnings and Precautions ( 5.3 )] Hypersensitivity Reactions [see Contraindications ( 4 ) a nd Warnings and Precautions ( 5.4 )] Increased Risk of Clinically Significant Effects with Pre-Existing Neuromuscular Disorders [see Warnings and Precautions ( 5.5 )] Dysphagia and Breathing Difficulties [see Warnings and Precautions ( 5.6 )] Pulmonary Effects of BOTOX in Patients with Compromised Respiratory Status Treated for Spasticity or for Detrusor Overactivity Associated with a Neurologic Condition [see Warnings and Precautions ( 5.7 )] Corneal Exposure and Ulceration in Patients Treated with BOTOX for Blepharospasm [see Warnings and Precautions ( 5.8 )] Retrobulbar Hemorrhages in Patients Treated with BOTOX for Strabismus [see Warnings and Precautions ( 5.9 )] Bronchitis and Upper Respiratory Tract Infections in Patients Treated for Spasticity [se e Warnings and Precautions ( 5.10 )] Autonomic Dysreflexia in Patients Treated for Detrusor Overactivity Associated with a Neurologic Condition [see Warnings and Precautions ( 5.11 )] Urinary Tract Infections in Patients with Overactive Bladder [see Warnings and Precautions ( 5.12 )] Urinary Retention in Patients Treated for Bladder Dysfunction [see Warnings and Precautions ( 5.13 )]
Mechanism of Action
BOTOX blocks neuromuscular transmission by binding to acceptor sites on motor or autonomic nerve terminals, entering the nerve terminals, and inhibiting the release of acetylcholine. This inhibition occurs as the neurotoxin cleaves SNAP-25, a protein integral to the successful docking and release of acetylcholine from vesicles situated within nerve endings. When injected intramuscularly at therapeutic doses, BOTOX produces partial chemical denervation of the muscle resulting in a localized reduction in muscle activity. In addition, the muscle may atrophy, axonal sprouting may occur, and extrajunctional acetylcholine receptors may develop. There is evidence that reinnervation of the muscle may occur, thus slowly reversing muscle denervation produced by BOTOX. When injected intradermally, BOTOX produces temporary chemical denervation of the sweat gland resulting in local reduction in sweating. Following intradetrusor injection, BOTOX affects the efferent pathways of detrusor activity via inhibition of acetylcholine release.
Overdosage
Excessive doses of BOTOX (onabotulinumtoxinA) for injection may be expected to produce neuromuscular weakness with a variety of symptoms. Symptoms of overdose are likely not to be present immediately following injection. Should accidental injection or oral ingestion occur or overdose be suspected, the person should be medically supervised for several weeks for signs and symptoms of systemic muscular weakness which could be local, or distant from the site of injection [see Boxed Warning and Wa rnings and Precautions ( 5.1 , 5.6 )]. These patients should be considered for further medical evaluation and appropriate medical therapy immediately instituted, which may include hospitalization. If the musculature of the oropharynx and esophagus are affected, aspiration may occur which may lead to development of aspiration pneumonia. If the respiratory muscles become paralyzed or sufficiently weakened, intubation and assisted respiration may be necessary until recovery takes place. Supportive care could involve the need for a tracheostomy and/or prolonged mechanical ventilation, in addition to other general supportive care. In the event of overdose, antitoxin raised against botulinum toxin is available from the Centers for Disease Control and Prevention (CDC) in Atlanta, GA. However, the antitoxin will not reverse any botulinum toxin-induced effects already apparent by the time of antitoxin administration. In the event of suspected or actual cases of botulinum toxin poisoning, please contact your local or state Health Department to process a request for antitoxin through the CDC. If you do not receive a response within 30 minutes, please contact the CDC directly at 1-770-488-7100. More information can be obtained at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5232a8.htm.