botox

Important safety information

Spread of toxin effects; swallowing and breathing difficulties can lead to death. Seek immediate medical attention if respiratory, speech or swallowing difficulties occur ( 5.1 , 5.6 ) Potency Units of BOTOX are not interchangeable with other preparations of botulinum toxin products ( 5.2 , 11 ) Potential serious adverse reactions after BOTOX injections for unapproved uses ( 5.3 ) Concomitant neuromuscular disorder may exacerbate clinical effects of treatment ( 5.5 ) Use with caution in patients with compromised respiratory function ( 5.6 , 5.7 , 5.10 ) Corneal exposure and ulceration due to reduced blinking may occur with BOTOX treatment of blepharospasm ( 5.8 ) Retrobulbar hemorrhages and compromised retinal circulation may occur with BOTOX treatment of strabismus ( 5.9 ) Bronchitis and upper respiratory tract infections in patients treated for spasticity ( 5.10 ) Urinary tract infections in patients treated for OAB ( 5.12 ) Urinary retention: Post-void residual urine volume should be monitored in patients treated for OAB or adult detrusor overactivity associated with a neurologic condition who do not catheterize routinely, particularly patients with multiple sclerosis or diabetes mellitus. ( 5.13 ) 5. 1 Spread of Toxin Effect Postmarketing safety data from BOTOX and other approved botulinum toxins suggest that botulinum toxin effects may, in some cases, be observed beyond the site of local injection. The symptoms are consistent with the mechanism of action of botulinum toxin and 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 related to spread of toxin effects. 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, and particularly in those patients who have an underlying condition that would predispose them to these symptoms. In unapproved uses and in approved indications, symptoms consistent with spread of toxin effect have been reported at doses comparable to or lower than doses used to treat cervical dystonia and spasticity. Patients or caregivers should be advised to seek immediate medical care if swallowing, speech or respiratory disorders occur. No definitive serious adverse event reports of distant spread of toxin effect associated with BOTOX for blepharospasm at the recommended dose (30 Units and below), severe primary axillary hyperhidrosis at the recommended dose (100 Units), strabismus, or for chronic migraine at the labeled doses have been reported. 5.2 Lack of Interchangeability between Botulinum Toxin Products 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 [see Description ( 11 )] . 5.3 Serious Adverse Reactions with Unapproved Use 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. 5.4 Hypersensitivity Reactions 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. 5.5 Increased Risk of Clinically Significant Effects with Pre-Existing Neuromuscular Disorders Individuals with peripheral motor neuropathic diseases, amyotrophic lateral sclerosis or neuromuscular junction disorders (e.g., 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 ( 5.1 , 5.6 ) ] . 5.6 Dysphagia and Breathing Difficulties 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 Warnings and Precautions ( 5.1 )]. Deaths as a complication of severe dysphagia have been reported after treatment with botulinum toxin. Dysphagia may persist for several months, and require use of a feeding tube to maintain adequate nutrition and hydration. Aspiration may result from severe dysphagia and is a particular risk when treating patients in whom swallowing or respiratory function is already compromised. Treatment with botulinum toxins may weaken neck muscles that serve as accessory muscles of ventilation. This may result in a critical loss of breathing capacity in patients with respiratory disorders who may have become dependent upon these accessory muscles. There have been postmarketing reports of serious breathing difficulties, including respiratory failure. Patients with smaller neck muscle mass and patients who require bilateral injections into the sternocleidomastoid muscle for the treatment of cervical dystonia have been reported to be at greater risk for dysphagia. Limiting the dose injected into the sternocleidomastoid muscle may reduce the occurrence of dysphagia. Injections into the levator scapulae may be associated with an increased risk of upper respiratory infection and dysphagia. Patients treated with botulinum toxin may require immediate medical attention should they develop problems with swallowing, speech or respiratory disorders. These reactions can occur within hours to weeks after injection with botulinum toxin [see Warnings and Precautions ( 5.1 )] . 5.7 Pulmonary Effects of BOTOX in Patients with Compromised Respiratory Status Treated for Spasticity or for Detrusor Overactivity Associated with a Neurologic Condition Patients with compromised respiratory status treated with BOTOX for spasticity should be monitored closely. In a double-blind, placebo-controlled, parallel group study in adult patients treated for upper limb spasticity with stable reduced pulmonary function (defined as FEV 1 40-80% of predicted value and FEV 1 /FVC ≤ 0.75), the event rate in change of Forced Vital Capacity (FVC) ≥15% or ≥20% was generally greater in patients treated with BOTOX than in patients treated with placebo (see Table 8 ). Table 8: Event Rate Per Patient Treatment Cycle Among Adult Upper Limb Spasticity Patients with Reduced Lung Function Who Experienced at Least a 15% or 20%…