Dysport - Product Information
|Condition:||Blepharospasm, Spasmodic Torticollis (Cervical Dystonia)|
|Form:||Intramuscular (IM), Powder|
|Ingredients:||abobotulinumtoxinA, human serum albumin, lactose monohydrate|
Summary Product Information
|Route of Administration||Dosage Form ⁄ Strength||Clinically Relevant Nonmedicinal Ingredients|
|Intramuscular||Sterile, lyophilized powder for reconstitution; 300 Units per vial|| Human Serum Albumin
For a complete listing see Dosage Forms, Composition and Packaging section.
Indications and Clinical Use
DYSPORT (abobotulinumtoxinA) is indicated for the temporary improvement in the appearance of moderate to severe glabellar lines in adult patients < 65 years of age.
Geriatrics (> 65 years of age)
The clinical data for subjects > 65 years of age are limited.
Pediatrics (< 18 years of age)
DYSPORT is not recommended for use in pediatric patients less than 18 years of age.
DYSPORT is contraindicated in patients:
- who are hypersensitive to abobotulinumtoxinA or to any ingredient in the formulation or component of the container. For a complete listing, see the Dosage Forms, Composition and Packaging section of the product monograph.
- with infection at the proposed injection sites.
- known to be allergic to cow′s milk protein.
Warnings and Precautions
Serious Warnings and Precautions
- The term “Unit” upon which dosing is based, is a specific measurement of toxin activity that is unique to Ipsen′s formulation of abobotulinumtoxinA. Therefore, the units used to describe DYSPORT activity are different from those used to describe that of other botulinum toxin preparations and the units representing DYSPORT activity are not interchangeable with other products.
- DYSPORT should only be administered by physicians with the appropriate qualifications and experience in the treatment and the use of required equipment.
- Follow the recommended dosage and frequency of administration for DYSPORT (See WARNINGS AND PRECAUTIONS, General and DOSAGE AND ADMINISTRATION).
Use DYSPORT only as directed.
Do not use dosage recommendations and potency units applied to other botulinum toxin products when using DYSPORT. Do not exceed the recommended dosage and frequency of administration of DYSPORT.
The safe and effective use of DYSPORT depends upon proper storage of the product, selection of the correct dose, reconstitution, and injection technique.
Caution should be exercised when administering DYSPORT to patients with neuromuscular junction disorders or when excessive weakness or atrophy is present in the target muscle, surgical alterations to the facial anatomy, marked facial asymmetry, inflammation at the injection site(s), ptosis, excessive dermatochalasis, deep dermal scarring, or thick sebaceous skin.
Muscle weakness remote to the site of injection and other serious adverse effects (e.g., dysphagia when injected into the neck region) have been very rarely reported in the cosmetic application. Patients with a history of underlying neurologic disorders, dysphagia and/or aspiration are at a greater risk of these effects and should be treated with extreme caution. The botulinum toxin product should be used under specialist supervision in these patients and should only be used if the benefit of treatment is considered to outweigh the risk.
Patients or caregivers should be advised to seek immediate medical care if swallowing, speech or respiratory disorders arise. Injection intervals of DYSPORT should be no more frequent than every three months. Indication-specific dosage and administration recommendations should be followed.
One Unit of DYSPORT corresponds to the calculated median intraperitoneal lethal dose (LD50) in mice. The method for performing the assay is specific to Ipsen′s product DYSPORT. Due to differences in specific details of this assay such as the vehicle, dilution scheme and laboratory protocols for the 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.
This product contains human serum 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. The theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD) also is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been identified for albumin.
Carcinogenesis and MutagenesisAnimal studies to evaluate the carcinogenic and genotoxic potential of DYSPORT have not been conducted. (See TOXICOLOGY section for more information).
CardiovascularIn study 06 – 01, 79 subjects were assessed by EKG for treatment-related QT interval changes. Following the use of DYSPORT for the treatment of glabellar lines, no QT⁄QTc prolongation was observed.
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.
Testing for antibodies to DYSPORT was performed in 1554 subjects who had up to nine cycles of treatment. Two subjects (0.13%) tested positive for binding antibodies at baseline. Three additional subjects tested positive for binding antibodies after receiving DYSPORT treatment. None of the patients tested positive for neutralizing antibodies.
As with all biologic products, an anaphylactic reaction may occur. Necessary precautions should be taken and epinephrine should be available.
NeurologicCaution should be exercised when administering DYSPORT to individuals with peripheral motor neuropathy (e.g., amyotrophic lateral sclerosis or motor neuropathy), facial palsy or neuromuscular junctional disorders (e.g., myasthenia gravis or Lambert-Eaton syndrome). Patients with neuromuscular disorders may be at an increased risk of clinically significant systemic effects such as severe dysphagia and respiratory compromise.
OphthalmologicRisk of ptosis can be mitigated by careful examination of the upper lid for separation or weakness of the levator palpebrae muscle (true ptosis), identification of lash ptosis, and evaluation of the range of lid excursion while manually depressing the frontalis to assess compensation.
SkinCaution should be exercised when administering DYSPORT to patients with inflammation at the injection site(s), deep dermal scarring, or thick sebaceous skin.
There are limited data from the use of abobotulinumtoxinA in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryo/fetal development, parturition or postnatal development other than at high doses causing maternal toxicity. The potential risk to pregnant women is unknown. DYSPORT should be used during pregnancy only if the benefit justifies any potential risk to the fetus. Caution should be exercised when prescribing to pregnant women.
It is not known whether this drug is excreted in human milk. The excretion of DYSPORT in milk has not been studied in animals. The use of DYSPORT during lactation is not recommended.
Pediatrics (< 18 years of age)DYSPORT is not recommended for use in children.
Geriatrics (> 65 years of age)The clinical data for subjects > 65 years of age are limited.
Monitoring and Laboratory TestsThere are no specific requirements for laboratory test monitoring when patients are treated with DYSPORT.
Adverse Drug Reaction Overview
Adverse reactions may occur within the first few days following injection and while generally transient may have a duration of several months.
Local muscle weakness represents the expected pharmacological action of botulinum toxin in muscle tissue; however, weakness of adjacent muscles associated with local diffusion and/or injection technique has been reported. Muscle weakness remote to the site of injection and other serious adverse effects (e.g., dysphagia when injected into the neck region) have been very rarely reported in the cosmetic application.
Clinical Trial Adverse Drug ReactionsBecause clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates.
Six clinical studies, including one Phase 2, three Phase 3, and two long-term safety studies were conducted with DYSPORT. The adverse reaction information from these clinical studies provides a basis for identifying the adverse reactions that appear to be related to drug use. Adverse reactions observed in these studies may not reflect those observed in clinical practice.
The adverse event data described below reflect exposure in 2,341 subjects who received 5,360 DYSPORT or placebo treatments (4,880 DYSPORT; 480 placebo). Some subjects received up to seven treatments with DYSPORT. The population was composed of subjects 19-80 years of age, and included 263 males and 2,078 females. Most subjects were Caucasian (79.8%). Subjects received 50-80 Unit doses of DYSPORT, injected intramuscularly in the glabellar region.
Adverse events of any cause were reported for 42% of the subjects treated with DYSPORT and 29% of the subjects treated with placebo. Treatment-emergent adverse events were generally mild to moderate in severity and the majority of events were considered unrelated or unlikely to be related to treatment. The most frequently reported adverse events were nasopharyngitis, headache, injection site pain, upper respiratory tract infection, and sinusitis. Subjects re-treated with DYSPORT demonstrated a comparable safety profile to that of the initial treatment. Table 1 displays treatment-emergent adverse events reported in >1% of subjects, regardless of causality. Repeat dose clinical studies have demonstrated safety for up to seven administrations of DYSPORT.
|Adverse Events by Preferred Term||DYSPORT
|Subjects with at least one treatment-emergent adverse event||852(42)||141(29)|
|Injection site pain||69(3)||7(1)|
|Upper respiratory tract infection||58(3)||4(<1)|
|Injection site bruising||34(2)||7(1)|
*Subjects who received treatment with placebo and DYSPORT are counted in both treatment columns.
The frequency of any ocular adverse events in the DYSPORT treatment group was low and decreased with subsequent treatments. The majority of eyelid ptosis events were mild to moderate in severity and resolved over several weeks. The incidence of eyelid ptosis did not increase in the long-term safety studies with multiple re-treatments at intervals ≥ three months.
The frequency of any ocular TEAE in the DYSPORT treatment group is low in Cycle 1 (3%), decreases to 2% in Cycles 2 and 3, and to 1% in Cycles 4 and 5.
Post-Market Adverse Drug ReactionsThere is extensive post-marketing experience for the treatment of upper facial lines. Adverse reactions are reported voluntarily from a population of uncertain size; thus, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure. The following adverse reactions have been identified during post-approval use: vertigo, eyelid ptosis, diplopia, vision blurred, photophobia, dysphagia, nausea, injection site pain, malaise, influenza-like illness, hypersensitivity, sinusitis, amyotrophy, burning sensation, facial paresis, dizziness, headache, hypoesthesia, erythema, and excessive granulation tissue.
Drug InteractionsNo specific interactions have been reported.
OverviewNo 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.
|Proper name of drug||Ref||Effect||Clinical Comment|
|aminoglycoside antibiotics or other medicinal products that interfere with neuromuscular transmission (e.g., curare-like agents, lincosamides, polymyxins, and anticholinesterases).||T||Theoretically, the effect of botulinum toxin may be potentiated.||The effect of botulinum toxin may be potentiated by aminoglycoside antibiotics or other drugs that interfere with neuromuscular transmission. Caution should be exercised when DYSPORT is used with aminoglycosides or any other drugs that interfere with neuromuscular transmission.|
|Different botulinum neurotoxin serotypes||T||Unknown||The effect of administering different botulinum neurotoxin serotypes at the same time or within several months of each other is unknown. Excessive weakness may be exacerbated by administration of another botulinum toxin prior to the resolution of the effects of a previously administered botulinum toxin.|
Drug-Food InteractionsInteractions with food have not been established.
Drug-Herb InteractionsInteractions with herbal products have not been established.
Drug-Laboratory InteractionsInteractions with laboratory tests have not been established.
Dosage and Administration
- For Intramuscular Use Only
- 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 should be administered at the recommended dose for each treatment area.
- Injection intervals of DYSPORT should be no more frequent than every three months.
Recommended Dose and Dosage Adjustment
Glabellar LinesTen (10) Units should be injected intramuscularly at each of five injection sites, 2 in each corrugator muscle and 1 in the procerus muscle for a total dose of 50 Units (see Figure 1).
The clinical effect of DYSPORT may last up to four months. Repeat dose clinical studies demonstrated continued efficacy with up to four repeated administrations; DYSPORT should be administered no more frequently than every three months.
Glabellar facial lines arise from the activity of the lateral corrugator and vertical procerus muscles. These can be readily identified by palpating the tensed muscle mass while having the patient frown. The corrugator depresses the skin creating a “furrowed” vertical line surrounded by tensed muscle (i.e., frown lines). The location, size, and use of the muscles vary markedly among individuals. Physicians administering DYSPORT must understand the relevant neuromuscular and/or orbital anatomy of the area involved and any alterations to the anatomy due to prior surgical procedures.
Risk of ptosis can be mitigated by careful examination of the upper lid for separation or weakness of the levator palpebrae muscle (true ptosis), identification of lash ptosis, and evaluation of the range of lid excursion while manually depressing the frontalis to assess compensation.
In order to reduce the complication of ptosis, the following steps should be taken:
- Avoid injection near the levator palpebrae superioris, particularly in patients with larger brow depressor complexes.
- Medial corrugator injections should be placed at least one centimeter above the bony supraorbital ridge.
- Ensure the injected volume⁄dose is accurate.
- Do not inject toxin closer than 1 centimeter above the central eyebrow.
To inject DYSPORT, advance the needle through the skin into the underlying muscle while applying finger pressure on the superior medial orbital rim. Inject patients with the recommended dose in five equally divided aliquots using a 30 gauge needle; two in each corrugator muscle and one in the procerus muscle (see Figure 1).
Figure 1. Glabellar Lines Injection Points
DYSPORT is supplied as a single-use vial.
Each 300 Unit vial of DYSPORT is to be reconstituted with either 1.5 or 2.5 mL of 0.9% sterile, preservative-free, saline prior to injection. The concentration of the resulting solution will be 10 Units per 0.05 mL or 10 Units per 0.08 mL, respectively, delivered in equally divided aliquots (see Table 3).
|Vial Size||Volume of Diluent to be Added to Vial||Nominal Concentration per mL|
|300 Units||1.5 mL||200 Units|
|300 Units||2.5 mL||120 Units|
Using a 21 gauge needle and aseptic technique, draw up sterile, preservative-free 0.9% saline. Insert the needle into the DYSPORT vial. The partial vacuum will begin to pull the saline into the vial. Any remaining required saline should be expressed into the vial manually. Do not use the vial if no vacuum is observed. Gently rotate the vial (do not shake), until the white substance is fully dissolved. Reconstituted DYSPORT should be a clear, colorless solution, free of particulate matter.
Draw DYSPORT into a sterile syringe. Expel any air bubbles in the syringe barrel. Remove the needle used to reconstitute the product and attach a 30 gauge needle.
Once reconstituted, DYSPORT should be stored in a refrigerator at 2–8°C protected from light and used within 24 hours. Do not freeze reconstituted DYSPORT. Discard the vial and needle in accordance with local regulations.
|For management of a suspected drug overdose, contact your regional Poison Control Centre.|
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 not likely 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.
In the event of suspected or actual cases of botulinum toxin poisoning, please contact your local Health Department to process a request for antitoxin. However, the antitoxin will not reverse any botulinum toxin-induced effects already apparent by the time of antitoxin administration.
Action and Clinical Pharmacology
Mechanism of Action
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.
The primary pharmacodynamic effect of DYSPORT is due to chemical denervation of the treated muscle resulting in a measurable decrease of the compound muscle action potential, causing a localized reduction of muscle activity.
DYSPORT is not expected to be present in the peripheral blood at measurable levels following intramuscular injection at the recommended doses. Using currently available analytical technology, it is not possible to detect DYSPORT in the peripheral blood following intramuscular injection at the recommended doses.
Duration of Effect
The clinical effect of DYSPORT may last up to four months. DYSPORT should not be administered more frequently than every three months. When used for re-treatment, DYSPORT should be reconstituted and injected using the same techniques as the initial treatment.
Storage and Stability
DYSPORT must be stored under refrigeration at 2–8°C. Protect from light.
Administer DYSPORT within 24 hours of reconstitution; during this period reconstituted DYSPORT should be stored under refrigeration at 2–8°C. Do not freeze after reconstitution.
Do not use after the expiration date on the vial.
Special Handling Instructions
All vials, including expired vials, or equipment used with DYSPORT should be disposed of carefully as is done with all medical waste.
Dosage Forms Composition and Packaging
DYSPORT for Injection is supplied in sterile, single-use, 3 mL glass vials. DYSPORT is available in a 300 Unit vial for reconstitution with 0.9% Sodium Chloride Injection USP (without preservative). Each vial contains 300 Units of lyophilized abobotulinumtoxinA, 125 micrograms human serum albumin and 2.5 mg lactose.
DYSPORT contains a unique hologram on the carton. If you do not see the hologram, do not use the product. Instead call [1-855-904-4884] between 7 a.m. and 5 p.m. Eastern Standard Time, Monday through Friday.