Since the active constituent in this drug is Clostridium botulinum toxin type A neurotoxin which is derived from Clostridium botulinum, the recommended dosages and frequency of administration should be observed with a full understanding of the precautions in use. Physicians administering the drug must understand the relevant neuromuscular anatomy of the area involved and any alterations to the anatomy due to prior surgical procedures. An understanding of standard electromyographic techniques is also required for the administration of the drug. The recommended dosage and frequency of administration for NEURONOX should not be exceeded.
Spread of toxin effect: In some cases, botulinum toxin effect may be observed beyond the site of local injection. The symptoms may include asthenia, generalized muscle weakness, diplopia, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence and breathing difficulties. 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. Symptoms with spread of toxin effect have been reported as doses comparable to or lower than doses used to treat cervical dystonia.
Hypersensitivity reactions: Serious and/or immediate hypersensitivity reactions have been rarely reported with other botulinum toxin products. These reactions include anaphylaxis, urticaria, soft tissue edema and dyspnea. One fatal case of anaphylaxis with other botulinum toxin product has been reported in which lidocaine was used as a diluent but the causal agent cannot be reliably determined. If such a reaction occurs, further injection of the drug should be discontinued and appropriate medical therapy should be immediately instituted.
Pre-existing neuromuscular disorders: Individuals with peripheral motor neuropathic diseases (e.g., amyotrophic lateral sclerosis, or motor neuropathy) or neuromuscular junctional disorders (e.g., myasthenia gravis or Lambert-Eaton syndrome) may be at increased risk of clinically significant systemic effects including severe dysphagia and respiratory compromise from typical doses of botulinum toxin injection. Published medical literature with other botulinum toxin product has reported rare cases of administration of a botulinum toxin to patients with known or unrecognized neuromuscular disorders where the patients have shown extreme sensitivity to the systemic effects of typical clinical doses. In some of these cases. dysphagia has lasted several months and required placement of a gastric feeding tube.
Dysphagia: Treatment of patients with Cervical Dystonia with all botulinum toxin products can result in swallowing difficulty and it is a common adverse reaction reported. In those patients, it has been rarely reported to use of a feeding tube due to severe dysphagia. Deaths as aspiration pneumonia have been reported after treatment with botulinum toxin that is developed after dysphagia.
There have been reports of adverse events involving the cardiovascular system, including arrhythmia and myocardial infarction, some with fatal outcomes in case of other botulinum toxin treatment. Some of these patients had risk factors including cardiovascular disease.
During the administration of other botulinum toxin product for the treatment of strabismus, retrobulbar hemorrhages sufficient to compromise retinal circulation have occurred from needle penetrations into the orbit. In order to decompress the orbit which can be easily affected, it is recommended that appropriate instruments be accessible. Ocular penetrations by needles have also occurred. An ophthalmoscope to diagnose this condition should be available. However, inducing paralysis in one or more extraocular muscles may produce spatial disorientation, double vision or past pointing. Covering the affected eye may alleviate these symptoms.
Corneal exposure and ulceration in patient treated with botulinum toxin products for blepharospasm Reduced blinking from botulinum toxin injection of the orbicularis muscle can lead to corneal exposure, persistent epithelial defect and corneal ulceration, especially in patients with VII nerve disorders. One case of corneal perforation in an aphakic eye requiring corneal grafting has occurred because of this effect. Careful testing of corneal sensation in eyes previously operated upon, avoidance of injection into the lower lid area to avoid ectropion, and vigorous treatment of any epithelial defect should be employed. This may require protective drops, ointment, therapeutic soft contact lenses, or closure of the eye by patching or other means.
Lack of interchangeability between Botulinum toxin products.
The potency units of biological activity of NEURONOX can not be compared to or convened into units of any other botulinum toxin products assessed with any other specific assay method.
Injections In or Near Vulnerable Anatomic Structures: Care should be taken when injecting in or near vulnerable anatomic structures. Serious adverse events including fatal outcomes have been reported in patients who had received other botulinum toxin products injected directly into salivary glands, the oro-lingual-pharyngeal region, esophagus and stomach. Some patients had pre-existing dysphagia or significant debility. (Safety and effectiveness have not been established for indications pertaining to these injection sites.) Pneumothorax associated with injection procedure has been reported following the administration of other botulinum toxin product near the thorax. Caution is warranted when injecting in proximity to the lung, particularly the apices.
Pulmonary Effects of botulinum toxin product in Patients with Compromised Respiratory Status Treated for Spasticity or for Detrusor Overactivity associated with a Neurologic Condition.
In Patients with compromised respiratory status treated with other botulinum toxin for upper limb spasticity, reduced lung function and upper respiratory tract infections were reported and patients with Detrusor Overactivity associated with a Neurologic Condition treated with Botox, reduced lung function was reported.
Bronchitis and Upper Respiratory Tract Infections in Patients Treated for Spasticity: Bronchitis was reported more frequently as an adverse reaction in patients treated for upper limb spasticity with botulinum toxin, compared to placebo. In patients with reduced lung function treated for upper limb spasticity, upper respiratory tract infections were also reported more frequently as adverse reactions in patients treated with botulinum toxin compared to placebo.