Class: Other Miscellaneous Therapeutic Agents
Chemical Name: Botulin A
Molecular Formula: C6760H10447N1743O2010S32
CAS Number: 93384-43-1
- Warning: Distant Spread Of Toxin Effect
See full prescribing information for complete boxed warning.
The effects of all botulinum toxin products, including prabotulinumtoxinA-xvfs, may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. 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. PrabotulinumtoxinA-xvfs is not approved for the treatment of spasticity or any conditions other than glabellar lines.
PrabotulinumtoxinA-xvfs is an acetylcholine release inhibitor and a neuromuscular blocking agent.
Uses for PrabotulinumtoxinA-xvfs
PrabotulinumtoxinA-xvfs has the following uses:
PrabotulinumtoxinA-xvfs is indicated for the temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity in adult patients.
PrabotulinumtoxinA-xvfs Dosage and Administration
PrabotulinumtoxinA-xvfs is available in the following dosage form(s) and strength(s):
For Injection: 100 units vacuum-dried powder in a single-dose vial for reconstitution.
It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:
Dosage and Administration
0.1 mL (4 units) prabotulinumtoxinA-xvfs by intramuscular injection into each of five sites, for a total dose of 20 units.
When used for retreatment, prabotulinumtoxinA-xvfs should be administered no more frequently than every three months. Consideration of the cumulative dose is necessary when treating adult patients with prabotulinumtoxinA-xvfs for glabellar lines if other botulinum toxin products are or have been used to treat other indications approved for those products.
Cautions for PrabotulinumtoxinA-xvfs
Hypersensitivity to any botulinum toxin preparation or to any of the components in the formulation.
Infection at the injection site.
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.
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.
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.
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.
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.
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.
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.
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, 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.
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.
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.
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).
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.
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.
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.
Risk Summary: The limited available data on prabotulinumtoxinA-xvfs use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes. An embryofetal developmental study conducted with prabotulinumtoxinA-xvfs in pregnant rats revealed no treatment-related effects to the developing fetus when prabotulinumtoxinA-xvfs was administered intramuscularly during organogenesis at doses up to 12 times the maximum recommended human dose (MRHD)
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Animal Data: In an embryofetal developmental study, intramuscular doses up to 4 units/kg prabotulinumtoxinA-xvfs were administered to pregnant rats once daily during organogenesis (gestation days 6 to 16). No maternal or embryofetal toxicities were observed at doses up to 4 units/kg (12 times the MRHD of 20 units, based on unit/kg comparison).
There is no information regarding the presence of prabotulinumtoxinA in human or animal milk, its effects on the breastfed infant or on milk production.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for prabotulinumtoxinA-xvfs and any potential adverse effects on the breastfed infant from prabotulinumtoxinA-xvfs or from the underlying maternal condition.
Safety and effectiveness in pediatric patients have not been established.
The two clinical trials of prabotulinumtoxinA-xvfs included 68 subjects age 65 and greater. No differences in safety or efficacy were observed between older and younger subjects; however, clinical studies of prabotulinumtoxinA-xvfs did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
Common Adverse Effects
The most common adverse reactions are headache (9.3%), eyelid ptosis (2%), upper respiratory tract infection (3%), and increased white blood cell count (1%).
It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:
Patients receiving concomitant treatment of prabotulinumtoxinA-xvfs and aminoglycosides or other agents interfering with neuromuscular transmission (e.g., curare-like agents), or muscle relaxants, should be observed closely because the effect of prabotulinumtoxinA-xvfs may be potentiated.
Mechanism Of Action
PrabotulinumtoxinA-xvfs blocks neuromuscular transmission by binding to acceptor sites on motor 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, prabotulinumtoxinA-xvfs 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 prabotulinumtoxinA-xvfs.
Advice to Patients
Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Advise patients to inform their doctor or pharmacist if they develop any unusual symptoms (including difficulty with swallowing, speaking or breathing), or if any known symptom persists or worsens.
Inform patients that prabotulinumtoxinA-xvfs injection may cause eye dryness. Advise patients to report symptoms of eye dryness (e.g., eye pain, eye irritation, photosensitivity, or changes in vision) to their doctor.
Inform patients that if loss of strength, muscle weakness, blurred vision or drooping eyelids occur, they should avoid driving a car or engaging in other potentially hazardous activities.
AHFSfirstRelease™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
AHFS Drug Information. © Copyright 2021, Selected Revisions February 25, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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