Spread Of Toxin Effect

Postmarketing safety data from other approved botulinum toxins suggest that botulinum toxin effects may 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, blurred vision 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. In unapproved uses, including upper limb spasticity in children and approved indications, symptoms consistent with spread of toxin effect have been reported at doses comparable to or lower than the maximum recommended total dose. PrabotulinumtoxinA-xvfs is not approved for the treatment of spasticity or any conditions other than glabellar lines. Patients or caregivers should be advised to seek immediate medical care if swallowing, speech or respiratory difficulties occur.(1)

Lack of Interchangeability Between Botulinum Toxin Products

The potency units of prabotulinumtoxinA-xvfs 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 prabotulinumtoxinA-xvfs cannot be compared to nor converted into units of any other botulinum toxin products assessed with any other specific assay method.(1)

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 botulinum toxin 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 botulinum toxin products 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 botulinum toxin products.(1)

Hypersensitivity Reactions

Serious and/or immediate hypersensitivity reactions have been reported for botulinum toxin products. These reactions include anaphylaxis, serum sickness, urticaria, soft tissue edema, and dyspnea. If such a reaction occurs, further injection of prabotulinumtoxinA-xvfs should be discontinued and appropriate medical therapy immediately instituted. The use of prabotulinumtoxinA-xvfs in patients with a known hypersensitivity to any botulinum neurotoxin or to any of the components in the formulation could lead to a life threatening allergic reaction.(1)

Cardiovascular System

There have been reports following administration of botulinum toxins of adverse events involving the cardiovascular system, including arrhythmia and myocardial infarction, some with fatal outcomes. Some of these patients had risk factors including pre-existing cardiovascular disease. Use caution when administering to patients with pre-existing cardiovascular disease.(1)

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) were excluded from the clinical studies of prabotulinumtoxinA-xvfs. Patients with neuromuscular disorders may be at increased risk of clinically significant effects including generalized muscle weakness, diplopia, ptosis, dysphonia, dysarthria, severe dysphagia and respiratory compromise from typical doses of prabotulinumtoxinA-xvfs.(1)

Dysphagia And Breathing Difficulties

Treatment with botulinum toxin products, including prabotulinumtoxinA-xvfs, can result in swallowing or breathing difficulties. Patients with preexisting swallowing or breathing difficulties may be more susceptible to these complications. In most cases, this has been a consequence of weakening of muscles in the area of injection that are involved in breathing or oropharyngeal muscles that control swallowing or breathing.(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.(1)

Treatment with botulinum toxins, including prabotulinumtoxinA-xvfs, 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 from other botulinum toxin products of serious breathing difficulties, including respiratory failure.(1)

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. Injections into the levator scapulae for the treatment of cervical dystonia may be associated with an increased risk of upper respiratory infection and dysphagia. PrabotulinumtoxinA-xvfs is not approved for the treatment of cervical dystonia.(1)

Patients treated with botulinum toxin products, including prabotulinumtoxinA-xvfs, 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.(1)

Pre-existing Conditions at the Injection Site

Caution should be used when prabotulinumtoxinA-xvfs treatment is used in the presence of inflammation at the proposed injection site(s) or when excessive weakness or atrophy is present in the target muscle(s).(1)

Caution should be used when prabotulinumtoxinA-xvfs treatment is used in patients who have marked facial asymmetry, ptosis, excessive dermatochalasis, deep dermal scarring, thick sebaceous skin or subjects who may not respond to 20 units of botulinum toxin (e.g., the inability to substantially lessen glabellar lines even by physically spreading them apart). Do not exceed the recommended dosage and frequency of administration of prabotulinumtoxinA-xvfs.(1)

Ophthalmic Adverse Reactions in Patients Treated with Botulinum Toxin Products

Dry eye has been reported with the use of botulinum toxin products in the treatment of glabellar lines. Reduced tear production, reduced blinking, and corneal disorders may occur with use of botulinum toxins, including prabotulinumtoxinA-xvfs. If symptoms of dry eye (e.g., eye irritation, photophobia, or visual changes) persist, consider referring patient to an ophthalmologist.(1)

Human Albumin and Transmission of Viral Diseases

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 or CJD or vCJD have ever been identified for licensed albumin or albumin contained in other licensed products.(1)

Specific Populations