Dysport 500iu Information
Dysport 500iu (Abobotulinumtoxina)
Dysport 500iu (Abobotulinumtoxina) Dosage And Administration
Reconstitution instructions are specific for each of the 300 Unit vial and the 500 Unit vial. These volumes yield concentrations specific for the use for each indication.
Dysport 500iu (Abobotulinumtoxina) Contraindications
DYSPORT™ is contraindicated in patients with known hypersensitivity to any botulinum toxin preparation or to any of the components in the formulation [].
This product may contain trace amounts of cow's milk protein. Patients known to be allergic to cow's milk protein should not be treated with DYSPORT™.
DYSPORT™ is contraindicated for use in patients with infection at the proposed injection site(s).
Dysport 500iu (Abobotulinumtoxina) Warnings And Precautions
The potency Units of DYSPORT™ 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 DYSPORT™ cannot be compared to or converted into units of any other botulinum toxin products assessed with any other specific assay method [].
Treatment with DYSPORT™ 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 swallowing. When distant effects occur, additional respiratory muscles may be involved [].
Deaths as a complication of severe dysphagia have been reported after treatment with botulinum toxin. Dysphagia may persist for several weeks, 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 of cervical dystonia 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 post-marketing reports of serious breathing difficulties, including respiratory failure, in cervical dystonia patients.
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 [].
Caution should be exercised when administering DYSPORT™ to patients with surgical alterations to the facial anatomy, excessive weakness or atrophy in the target muscle(s), marked facial asymmetry, inflammation at the injection site(s), ptosis, excessive dermatochalasis, deep dermal scarring, thick sebaceous skin [] or the inability to substantially lessen glabellar lines by physically spreading them apart [].
Do not exceed the recommended dosage and frequency of administration of DYSPORT™. In clinical trials, subjects who received a higher dose of DYSPORT™ had an increased incidence of eyelid ptosis.
Dysport 500iu (Abobotulinumtoxina) Adverse Reactions
The following adverse reactions to DYSPORT™ are discussed in greater detail in other sections of the labeling.
As with all therapeutic proteins, there is a potential for immunogenicity.
The incidence of antibody formation is highly dependent on the sensitivity and specificity of the assay. In addition, the observed incidence of antibody positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies across products in this class may be misleading.
Dysport 500iu (Abobotulinumtoxina) Drug Interactions
No formal drug interaction studies have been conducted with DYSPORT™.
Patients treated concomitantly with botulinum toxins and aminoglycosides or other agents interfering with neuromuscular transmission (e.g., curare-like agents) should be observed closely because the effect of the botulinum toxin may be potentiated. Use of anticholinergic drugs after administration of DYSPORT™ may potentiate systemic anticholinergic effects such as blurred vision.
The effect of administering different botulinum neurotoxin products at the same time or within several months of each other is unknown. Excessive weakness may be exacerbated by another administration of botulinum toxin prior to the resolution of the effects of a previously administered botulinum toxin.
Excessive weakness may also be exaggerated by administration of a muscle relaxant before or after administration of DYSPORT™.
Dysport 500iu (Abobotulinumtoxina) Overdosage
Excessive doses of DYSPORT™ may be expected to produce neuromuscular weakness with a variety of symptoms. Respiratory support may be required where excessive doses cause paralysis of respiratory muscles. In the event of overdose, the patient should be medically monitored for symptoms of excessive muscle weakness or muscle paralysis []. Symptomatic treatment may be necessary.
Symptoms of overdose are likely not to be present immediately following injection. Should accidental injection or oral ingestion occur, the person should be medically supervised for several weeks for signs and symptoms of excessive muscle weakness or paralysis.
There is no significant information regarding overdose from clinical studies in cervical dystonia. Doses exceeding 1000 Units of DYSPORT™ were rarely studied in clinical settings for any indication.
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 770-488-7100. More information can be obtained at .
Dysport 500iu (Abobotulinumtoxina) Description
Botulinum toxin type A, the active ingredient in DYSPORT™ (abobotulinumtoxinA), is a purified neurotoxin type A complex produced by fermentation of the bacterium type A, Hall Strain. It is purified from the culture supernatant by a series of precipitation, dialysis, and chromatography steps. The neurotoxin complex is composed of the neurotoxin, hemagglutinin proteins and non-toxin non-hemagglutinin protein.
DYSPORT™ is supplied in a single-use, sterile vial for reconstitution intended for intramuscular injection. Each vial contains 500 or 300 Units of lyophilized abobotulinumtoxinA, 125 micrograms human serum albumin and 2.5 mg lactose. DYSPORT™ may contain trace amounts of cow's milk proteins [].
One unit of DYSPORT™ corresponds to the calculated median lethal intraperitoneal dose (LD50) in mice. The method for performing the assay is specific to Ipsen's product DYSPORT™. Due to differences in specific details such as vehicle, dilution scheme and laboratory protocols for various mouse LD50 assays, Units of biological activity of DYSPORT™ are not interchangeable with Units of any other botulinum toxin or any toxin assessed with any other specific assay method [].
Dysport 500iu (Abobotulinumtoxina) Clinical Pharmacology
DYSPORT™ inhibits release of the neurotransmitter, acetylcholine, from peripheral cholinergic nerve endings. Toxin activity occurs in the following sequence: Toxin heavy chain mediated binding to specific surface receptors on nerve endings, internalization of the toxin by receptor mediated endocytosis, pH-induced translocation of the toxin light chain to the cell cytosol and cleavage of SNAP25 leading to intracellular blockage of neurotransmitter exocytosis into the neuromuscular junction. This accounts for the therapeutic utility of the toxin in diseases characterized by excessive efferent activity in motor nerves.
Recovery of transmission occurs gradually as the neuromuscular junction recovers from SNAP25 cleavage and as new nerve endings are formed.
Dysport 500iu (Abobotulinumtoxina) Clinical Studies
The efficacy of DYSPORT™ was evaluated in two well-controlled, randomized, double-blind, placebo controlled, single dose, parallel group studies in treatment-naïve cervical dystonia patients. The principal analyses from these trials provide the primary demonstration of efficacy involving 252 patients (121 on DYSPORT™, 131 on placebo) with 36% male and 64% female. Ninety-nine percent of the patients were Caucasian.
In both placebo controlled studies (Study 1 and Study 2), a dose of 500 Units DYSPORT™ was given by intramuscular injection divided among two to four affected muscles. These studies were followed by long-term open label extensions that allowed titration in 250 Unit steps to doses in a range of 250 to 1000 Units, after the initial dose of 500 Units. In the extension studies, re-treatment was determined by clinical need after a minimum of 12 weeks. The median time to re-treatment was 14 weeks and 18 weeks for the 75 percentile.
The primary assessment of effi cacy was based on the total Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) change from baseline at Week 4 for both studies. The scale evaluates the severity of dystonia, patient perceived disability from dystonia, and pain. The adjusted mean change from baseline in the TWSTRS total score was statistically significantly greater for the DYSPORT™ group than the placebo group at Weeks 4 in both studies .
Analyses by gender, weight, geographic region, underlying pain, cervical dystonia severity at baseline and history of treatment with botulinum toxin did not show any meaningful differences between groups.
Table 5 indicates the average DYSPORT™ dose, and percentage of total dose, injected into specific muscles in the pivotal clinical trials.
Three double-blind, randomized, placebo-controlled, clinical studies evaluated the efficacy of DYSPORT™ for use in the temporary improvement of the appearance of moderate to severe glabellar lines. These three studies enrolled healthy adults (ages 19–75) with glabellar lines of at least moderate severity at maximum frown. Subjects were excluded if they had marked ptosis, deep dermal scarring, or a substantial inability to lessen glabellar lines, even by physically spreading them apart. The subjects in these studies received either DYSPORT™ or placebo. The total dose was delivered in equally divided aliquots to specified injection sites .
Investigators and subjects assessed efficacy at maximum frown by using a 4-point scale (none, mild, moderate, severe).
Overall treatment success was defined as post-treatment glabellar line severity of none or mild with at least 2 grade improvement from Baseline for the combined investigator and subject assessments (composite assessment) on Day 30 . Additional endpoints for each of the studies were post-treatment glabellar line severity of none or mild with at least a 1 grade improvement from Baseline for the separate investigator and subject assessments on Day 30.
After completion of the randomized studies, subjects were offered participation in a two-year, open-label retreatment study to assess the safety of multiple treatments.
Treatment with DYSPORT™ reduced the severity of glabellar lines for up to four months.
Dysport 500iu (Abobotulinumtoxina) How Supplied/storage And Handling
DYSPORT™ for Injection is supplied in a sterile, single-use, 3 mL glass vial. DYSPORT™ must be stored under refrigeration at 2–8°C (36–46°F). Protect from light.
Administer DYSPORT™ within 4 hours of reconstitution; during this period reconstituted DYSPORT™ should be stored under refrigeration at 2–8°C (36–46°F). Do not freeze after reconstitution.
Do not use after the expiration date on the vial. All vials, including expired vials, or equipment used with DYSPORT™ should be disposed of carefully as is done with all medical waste.
DYSPORT™ contains a unique hologram on the vial label and carton. If you do not see the hologram, do not use the product. Instead contact 877-397-7671.
Cervical Dystonia
Glabellar Lines
Dysport 500iu (Abobotulinumtoxina) Patient Counseling Information
The physician should provide a copy of the FDA-Approved Patient Medication Guide and review the contents with the patient. Patients should be advised 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.
Patients should be counseled 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.
Dysport 500iu (Abobotulinumtoxina)
Dysport 500iu (Abobotulinumtoxina)
Dysport 500iu (Abobotulinumtoxina)
Dysport 500iu (Abobotulinumtoxina)
