Dysport
Botulinum Toxin Type A · Injection, Powder, Lyophilized, For Solution · Intramuscular
Uses
1 INDICATIONS AND USAGE DYSPORT is an acetylcholine release inhibitor and neuromuscular blocking agent indicated for: the treatment of cervical dystonia in adults ( 1.1 ) the temporary improvement in the appearance of moderate to severe glabellar lines associated with procerus and corrugator muscle activity in adults < 65 years of age ( 1.2 ) The treatment of spasticity in patients 2 years of age and older ( 1.3 ) 1.1 Cervical Dystonia DYSPORT is indicated for the treatment of cervical dystonia in adults. 1.2 Glabellar Lines DYSPORT is indicated for the temporary improvement in the appearance of moderate to severe glabellar lines associated with procerus and corrugator muscle activity in adults less than 65 years of age. 1.3 Spasticity DYSPORT is indicated for the treatment of spasticity in patients 2 years of age and older.
Dosage and administration
Preparation of DYSPORT Solution for Administration ( 2.2 ) Once reconstituted, store in original container in a refrigerator 2°C to 8°C (36°F to 46°F) and use within 24 hours Do not freeze after reconstitution Reconstitution instructions are specific for the 300 Unit and 500 Unit vials Reconstituted DYSPORT is intended for intramuscular injection only. After reconstitution, DYSPORT should be used for only one injection session and for only one patient. Cervical Dystonia ( 2.3 )
• Initial dose is 500 Units given intramuscularly as a divided dose among the affected muscles
• Re-treatment every 12 to 16 weeks or longer, as necessary, based on return of clinical symptoms with doses administered between 250 and 1000 Units to optimize clinical benefit
• Re-treatment should not occur in intervals of less than 12 weeks
• Titrate in 250 Unit steps according to patient's response Glabellar Lines ( 2.4 ) Administer a total dose of 50 Units, divided in five equal aliquots of 10 Units each, intramuscularly to affected muscles to achieve clinical effect Re-treatment should be administered no more frequently than every 3 months Spasticity in Adults ( 2.5 ) Select dose based on muscles affected, severity of spasticity, and treatment and adverse reaction history botulinum toxins Dosing for upper limb spasticity: between 500 Units and 1000 Units Dosing for lower limb spasticity: up to 1500 Units The maximum recommended total dose per treatment session (upper and lower limb combined) in adults is 1500 Units Re-treatment, based on return of clinical symptoms, should not occur in intervals of less than 12 weeks Spasticity in Pediatric Patients ( 2.6 ) Select dose based on the affected muscle, severity of spasticity, and treatment and adverse reaction history with all botulinum toxins. Recommended dosing for upper limb spasticity: 8 Units/kg to 16 Units/kg per limb. The maximum recommended total dose administered per treatment session must not exceed 16 Units/kg or 640 Units, whichever is lower. Recommended dosing for lower limb spasticity: 10 Units/kg to 15 Units/kg per limb. Total dose per treatment session must not exceed 15 Units/kg for unilateral lower limb injections, 30 Units/kg for bilateral injections, or 1000 Units, whichever is lower. The maximum recommended total dose per treatment session is 30 Units/kg or 1000 Units, whichever is lower. Re-treatment, based on return of clinical symptoms, should not occur in intervals of less than 3 months. 2.1 Instructions for Safe Use The potency units of DYSPORT 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 [ see Warnings and Precautions (5.2) and Description (11) ]. Reconstituted DYSPORT is intended for intramuscular injection only. 2.2 Preparation of Dysport Solution for Administration DYSPORT is supplied as a dry powder, in single-dose 300 Unit and 500 Unit vials, which must be reconstituted with preservative-free 0.9% Sodium Chloride Injection, USP using aseptic technique prior to intramuscular injection. Table 1 provides dilution instructions for the 300 Unit and 500 Unit vials, depending on the desired final concentration. The desired final concentration after dilution varies depending on the indication (see Table 2 for the recommended solution concentration after dilution). Table 1: Dilution Instructions for DYSPORT Vials (500 Units and 300 Units) Diluent Preservative-free 0.9% Sodium Chloride Injection, USP Only per 500 Unit Vial Resulting Dose Unites per 0.1 mL DIluent per 300 Unit Vial Resulting Dose Units per 0.1 mL 1 mL 50 Units 0.6 mL 50 Units 2 mL 25 Units -- -- 2.5 mL 20 Units 1.5 mL 20 Units -- -- 2.5 mL 12 Units 5 mL ‡ 10 Units 3 mL 10 Units Note: These dilutions are calculated for an injection volume of 0.1 mL. A decrease or increase in the DYSPORT dose is also possible by administering a smaller or larger injection volume (i.e., 0.05 mL (50% decrease in dose), 0.08% (20% decrease in dose) or 0.15 mL (50% increase in dose)). ‡ When using 5 mL of diluent for a 500 Unit vial of DYSPORT, no more than 2.5 mL of 0.9% Sodium Chloride Injection, USP should be introduced into the vial. Complete the following steps: Reconstitute a 500 Unit vial of DYSPORT with 2.5 mL of Preservative-free 0.9% Sodium Chloride Injection, USP, gently mix, and set the vital aside. Withdraw 2.5 mL of Preservative-free 0.9 Sodium Chloride Infection, USP into a 5 mL syringe Take the 5 mL syringe with 2.5 ml Preservative-free Sodium Chloride Injection, USP and draw up the DYSPORT solution from the reconstituted vial without inverting and mix gently. The resulting concentration will be 10 units/0.1 mL Use immediately after reconstitution in the syringe. Dispose of any unused 0.9% Sodium Chloride Injection, USP. Using an appropriately sized sterile syringe, needle and aseptic technique, draw up the required amount of sterile, preservative-free 0.9% Sodium Chloride Injection, USP (see Table 1 ). 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 partial vacuum is observed. Swirl gently to dissolve. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Reconstituted DYSPORT should be a clear, colorless solution, free of particulate matter, otherwise it should not be injected. Expel any air bubbles in the syringe barrel. Remove the needle used to reconstitute the product and attach an appropriately sized new sterile needle for injection. After reconstitution, DYSPORT should be used for only one injection session and for only one patient. Discard any unused portion.
Dosage forms and strengths
For injection: 300 Units or 500 Units of lyophilized powder in a single-dose vial for reconstitution with preservative-free 0.9% Sodium Chloride Injection, USP.
• For Injection: 300 Units or 500 Units lyophilized powder in a single-dose vial ( 3 )
Contraindications
4 CONTRAINDICATIONS DYSPORT is contraindicated in patients with: Known hypersensitivity to any botulinum toxin products, cow's milk protein, or to any of the components in the formulation [ see Warnings and Precautions (5.3) ] . This product may contain trace amounts of cow's milk protein [ see Description (11) ] . Infection at the proposed injection site(s).
• Hypersensitivity to:
• any botulinum toxin product or excipients ( 4 , 5.3 )
• cow's milk protein ( 4 , 5.3 )
• Infection at the proposed injection site(s) ( 4 )
Warnings and precautions
The potency units of DYSPORT are not interchangeable with other preparations of botulinum toxin products ( 5.2 ) Immediate medical attention may be required in cases of respiratory, speech or swallowing difficulties ( 5.4 ) Recommended dose and frequency of administration should not be exceeded ( 5.5 ) Dry eye may occur with glabellar line treatment; if symptoms persist, consider referring patient to an ophthalmologist ( 5.6 ) Concomitant neuromuscular disorder may exacerbate clinical effects of treatment ( 5.7 ) 5.1 Spread of Toxin Effect Postmarketing safety data from DYSPORTand other approved botulinum toxins suggest that botulinum toxin effects may, in some cases, 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, blurred vision, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence 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. 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, particularly in those patients who have underlying conditions that would predispose them to these symptoms. In unapproved uses 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. 5.2 Lack of Interchangeability between Botulinum Toxin Products 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 [see Description (11)]. 5.3 Hypersensitivity Reactions Serious hypersensitivity reactions have been reported with DYSPORT. Hypersensitivity reactions include anaphylaxis, serum sickness, urticaria, soft tissue edema, and dyspnea. If such a serious hypersensitivity reaction occurs, discontinue further injection of DYSPORT and institute appropriate medical therapy immediately. 5.4 Dysphagia and Breathing Difficulties 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 [ see Boxed Warning and Warnings and Precautions (5.2) ] . 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. 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 [see Boxed Warning, Warnings and Precautions (5.2 ), Adverse Reactions (6.1 ), Clinical Pharmacology (12.2 )]. 5.5 Facial Anatomy in the Treatment of Glabellar Lines Caution should be exercised when administering DYSPORT to patients with surgical alterations to the facial anatomy, marked facial asymmetry, inflammation at the injection site(s), ptosis, excessive dermatochalasis, deep dermal scarring, thick sebaceous skin [ see Dosage and Administration (2.4) ] or the inability to substantially lessen glabellar lines by physically spreading them apart [ see Clinical Studies (14.2) ] . 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. 5.6 Dry Eye with the Treatment of Glabellar Lines Dry eye has been reported with the use of DYSPORT in the treatment of glabellar lines [see Adverse Reactions (6.3)]. Reduced tear production, reduced blinking, and corneal disorders, may occur with use of botulinum toxins, including DYSPORT. If symptoms of dry eye (e.g., eye irritation, photophobia, or visual changes) persist, consider referring patient to an opththalmologist [ see Boxed Warning and Warnings and Precautions 5.2 ]. 5.7 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) should be monitored particularly closely when given botulinum toxin. Patients with neuromuscular disorders may be at increased risk of clinically significant effects including severe dysphagia and respiratory compromise from typical doses of DYSPORT [ see Adverse Reactions (6.1) ] . 5.8 Human Albumin and Transmission of Viral Diseases This product contains albumin, a derivative of human blood.
Side effects
The following serious adverse reactions are discussed below and elsewhere in labeling: Spread of Toxin Effect [ see Warning s and Precautions (5.1)] Lack of Interchangeability between Botulinum Toxin Products [ see Warnings and Precautions (5.2) ] Hypersensitivity Reactions [ see Warnings and Precautions (5.3) ] Dysphagia and Breathing Difficulties [ see Warnings and Precautions (5.4) ] Facial Anatomy in the Treatment of Glabellar Lines [ see Warnings and Precautions (5.5) ] Dry Eye with the Treatment of Glabellar Lines [see Warnings and Precautions (5.6) ] Pre-existing Neuromuscular Disorders [ see Warnings and Precautions (5.7) ] Human Albumin and Transmission of Viral Diseases [ see Warnings and Precautions (5.8) ] Intradermal Immune Reaction [ see Warnings and Precautions (5.9) ] Pre-existing Conditions at the Injection Site [ See Warnings and Precautions (5.10) ] Most commonly observed adverse reactions are ( 6.1 ): Cervical Dystonia (≥ 5%): muscular weakness, dysphagia, dry mouth, injection site discomfort, fatigue, headache, musculoskeletal pain, dysphonia, injection site pain and eye disorders Glabellar Lines (≥2%): nasopharyngitis, headache, injection site pain, injection site reaction, upper respiratory tract infection, eyelid edema, eyelid ptosis, sinusitis, nausea, and blood present in urine Spasticity in Adults Upper limb spasticity (≥ 4%): muscular weakness Lower limb spasticity (≥ 5%): falls, muscular weakness, and pain in extremity Spasticity in Pediatric Patients Upper limb spasticity (≥10%): upper respiratory tract infection and pharyngitis Lower limb spasticity ((≥10%): nasopharyngitis, cough, and pyrexia To report SUSPECTED ADVERSE REACTIONS, contact Ipsen Biopharmaceuticals, Inc. at 855-463-5127 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Cervical Dystonia The data described below reflect exposure to DYSPORT in 446 cervical dystonia patients in 7 studies. Of these, two studies were randomized, double-blind, single treatment, placebo-controlled studies with subsequent optional open-label treatment in which dose optimization (250 to 1000 Units per treatment) over the course of 5 treatment cycles was allowed [see Clinical Studies (14.1)]. The population was almost entirely Caucasian (99%) with a median age of 51 years (range 18–82 years). Most patients (87%) were less than 65 years of age; 58.4% were women. Common Adverse Reactions The most commonly reported adverse reactions (occurring in 5% or more of patients who received 500 Units of DYSPORT in the placebo-controlled clinical trials) in cervical dystonia patients were: muscular weakness, dysphagia, dry mouth, injection site discomfort, fatigue, headache, musculoskeletal pain, dysphonia, injection site pain and eye disorders (consisting of blurred vision, diplopia, and reduced visual acuity and accommodation). Other than injection site reactions, most adverse reactions became noticeable about one week after treatment and lasted several weeks. The rates of adverse reactions were higher in the combined controlled and open-label experience than in the placebo-controlled trials. During the clinical studies, two patients (<1%) experienced adverse reactions leading to withdrawal. One patient experienced disturbance in attention, eyelid disorder, feeling abnormal and headache, and one patient experienced dysphagia. Table 7 compares the incidence of the most frequent adverse reactions from a single treatment cycle of 500 Units of DYSPORT compared to placebo [ see Clinical Studies (14.1) ]. Table 7: Most Common Adverse Reactions (≥ 5%) and Greater than Placebo in the Pooled, Double-blind, Placebo-Controlled Phase of Clinical Trials in Patients with Cervical Dystonia Adverse Reactions DYSPORT 500 Units (N=173) Placebo (N=182) % % Any Adverse Reaction 61 51 General disorders and administration site conditions Injection site discomfort 13 8 Fatigue 12 10 Injection site pain 5 4 Musculoskeletal and connective tissue disorders Muscular weakness 16 4 Musculoskeletal pain 7 3 Gastrointestinal disorders Dysphagia 15 4 Dry Mouth 13 7 Nervous system disorders Headache 11 9 Respiratory, thoracic and mediastinal disorders Dysphonia 6 2 Eye Disorders The following preferred terms were reported: vision blurred, diplopia, visual acuity reduced, eye pain, eyelid disorder, accommodation disorder, dry eye, eye pruritus. 7 2 Dose-response relationships for common adverse reactions in a randomized multiple fixed-dose study in which the total dose was divided between two muscles (the sternocleidomastoid and splenius capitis) are shown in Table 8. Table 8: Common Adverse Reactions by Dose in Fixed-dose Study in Patients with Cervical Dystonia Adverse Reactions DYSPORT Dose 250 Units % 500 Units % 1000 Units % Placebo % Any Adverse Reaction 37 65 83 30 Dysphagia 21 29 39 5 Dry Mouth 21 18 39 10 Muscular Weakness 11 12 56 0 Injection Site Discomfort 5 18 22 10 Dysphonia 0 18 28 0 Facial Paresis 5 0 11 0 Eye Disorder The following preferred terms were reported: vision blurred, diplopia, visual acuity reduced, eye pain, eyelid disorder, accommodation disorder, dry eye, eye pruritus 0 6 17 0 Injection Site Reactions Injection site discomfort and injection site pain were common adverse reactions following DYSPORT administration. Less Common Adverse Reactions The following adverse reactions were reported less frequently (<5%). Breathing Difficulty Breathing difficulties were reported by approximately 3% of patients following DYSPORT administration and in 1% of placebo patients in clinical trials during the double-blind phase. These consisted mainly of dyspnea.
Drug interactions
Concomitant use of DYSPORT and aminoglycosides or other agents interfering with neuromuscular transmission or muscle relaxants, should be observed closely because the effect of DYSPORT may be potentiated (7.1, 7.4) Anticholinergic drugs may potentiate systemic anticholinergic effects (7.2) The effect of administering different botulinum neurotoxins during the course of treatment with DYSPORT is unknown (7.3) 7.1 Aminoglycosides and Other Agents Interfering with Neuromuscular Transmission Co-administration of DYSPORT and aminoglycosides or other agents interfering with neuromuscular transmission (e.g., curare-like agents) should only be performed with caution because the effect of the botulinum toxin may be potentiated. If co-administered, observe the patient closely. 7.2 Anticholinergic Drugs Use of anticholinergic drugs after administration of DYSPORT may potentiate systemic anticholinergic effects such as blurred vision. 7.3 Other Botulinum Neurotoxin Products The effect of administering botulinum neurotoxin products including DYSPORT, 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. 7.4 Muscle Relaxants Excessive weakness may also be exaggerated by administration of a muscle relaxant before or after administration of DYSPORT.
Use in specific populations
Administer DYSPORT with care in elderly patients, reflecting the greater frequency of concomitant disease and other drug therapy ( 8.5 ) 8.1 Pregnancy Risk Summary There are no adequate and well-controlled clinical studies with DYSPORT in pregnant women. DYSPORT should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. DYSPORT produced embryo-fetal toxicity in relation to maternal toxicity when given to pregnant rats and rabbits at doses lower than or similar to the maximum recommended human dose (MRHD) of 1000 Units on a body weight (Units/kg) basis ( see Data ). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data In a study in which pregnant rats received daily intramuscular injections of DYSPORT (2.2, 6.6, or 22 Units/kg on gestation days 6 through 17 or intermittently 44 Units/kg on gestation days 6 and 12 only) during organogenesis, increased early embryonic death was observed with both schedules at the highest tested doses (22 and 44 Units/kg), which were associated with maternal toxicity. The no-effect dose for embryo-fetal developmental toxicity was 2.2 Units/kg (less than maximum recommended human [MRHD] on a body weight basis). In a study in which pregnant rabbits received daily intramuscular injections of DYSPORT® (0.3, 3.3 or 6.7 Units/kg) on gestation days 6 through 19 or intermittently (13.3 Units/kg on gestation days 6 and 13 only) during organogenesis, no embryofetal data were available at the highest dose administered daily (6.7 Units/kg) because of premature death in all does at that dose. At the lower daily doses or with intermittent dosing, no adverse developmental effects were observed. All dosed for which data were available are less than the MRHD on a body weight basis. In a study in which pregnant rats received 6 weekly intramuscular injections of DYSPORT (4.4, 11.1, 22.2, or 44 Units/kg) beginning on day 6 of gestation and continuing through parturition to weaning, an increase in stillbirths was observed at the highest dose tested, which was maternally toxic. The no-effect dose for pre- and post-natal development toxicity was 22.2 Units/kg (similar to the MRHD). 8.2 Lactation Risk Summary There are no data on the presence of DYSPORT in human or animal milk, the effects on the breastfed infant, or the effects on milk production. The development and health benefits of breastfeeding should be considered along with the mother's clinical need for DYSPORT and any potential adverse effects on the breastfed infant from DYSPORT or from the underlying maternal condition. 8.3 Females and Males of Reproductive Potential Infertility In rats, DYSPORT produced adverse effects on mating behavior and fertility [ see Nonclinical Toxicology (13.1 )]. 8.4 Pediatric Use Cervical Dystonia Safety and effectiveness in pediatric patients have not been established [see Boxed Warning and Warnings and Precautions (5.2) ]. Glabellar Lines DYSPORT is not recommended for use in pediatric patients less than 18 years of age. Spasticity Safety and effectiveness have been established in pediatric patients 2 years of age and older [see Warnings and Precautions (5.1), Adverse Reactions (6.1), and Clinical Studies (14.4)]. The safety and effectiveness of DYSPORT have been established by evidence from adequate and well-controlled studies of DYSPORT in patients 2 years of age and older with upper and lower limb spasticity. The safety and effectiveness of DYSPORT injected into proximal muscles of the lower limb for the treatment of spasticity in pediatric patients has not been established [see Boxed Warning, Warnings and Precautions (5.2), and Adverse Reactions (6.1)]. Safety and effectiveness in pediatric .below the age of 2 years have not been established [see Boxed Warning and Warnings and Precautions (5.2)]. Juvenile Animal Data In a study in which juvenile rats received a single intramuscular injection of DYSPORT (1, 3 or 10 Units/animal) on postnatal day 21, decreased growth and bone length (injected and contralateral limbs), delayed sexual maturation, and decreased fertility were observed at the highest dose tested, which was associated with excessive toxicity during the first week after dosing. In a study in which juvenile rats received weekly intramuscular injections of DYSPORT (0.1, 0.3, or 1.0 Units/animal) from postnatal day 21 to 13 weeks of age, decreases in bone mineral content in the injected limb, associated with atrophy of injected and adjacent muscles, were observed at the highest dose tested. No adverse effects were observed on neurobehavioral development. However, dose levels were not adjusted for growth of the pups. On a body weight basis, the doses at the end of the dosing period were approximately 15% of those at initiation of dosing. Therefore, the effects of DYSPORT throughout postnatal development were not adequately evaluated. 8.5 Geriatric Use Cervical Dystonia There were insufficient numbers of patients aged 65 years and over in the clinical studies to determine whether they respond differently than younger patients. In general, elderly patients should be observed to evaluate their tolerability of DYSPORT, due to the greater frequency of concomitant disease and other drug therapy [ see Dosage and Administration (2.3) ]. Glabellar Lines Of the total number of subjects in the placebo-controlled clinical studies of DYSPORT, 8 (1%) were 65 years and over. Efficacy was not observed in subjects aged 65 years and over [ see Clinical Studies (14.2) ]. For the entire safety database of geriatric subjects, although there was no increase in the incidence of eyelid ptosis, geriatric subjects did have an increase in the number of ocular adverse reactions compared to younger subjects (11% vs.
Pregnancy
8.1 Pregnancy Risk Summary There are no adequate and well-controlled clinical studies with DYSPORT in pregnant women. DYSPORT should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. DYSPORT produced embryo-fetal toxicity in relation to maternal toxicity when given to pregnant rats and rabbits at doses lower than or similar to the maximum recommended human dose (MRHD) of 1000 Units on a body weight (Units/kg) basis ( see Data ). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data In a study in which pregnant rats received daily intramuscular injections of DYSPORT (2.2, 6.6, or 22 Units/kg on gestation days 6 through 17 or intermittently 44 Units/kg on gestation days 6 and 12 only) during organogenesis, increased early embryonic death was observed with both schedules at the highest tested doses (22 and 44 Units/kg), which were associated with maternal toxicity. The no-effect dose for embryo-fetal developmental toxicity was 2.2 Units/kg (less than maximum recommended human [MRHD] on a body weight basis). In a study in which pregnant rabbits received daily intramuscular injections of DYSPORT® (0.3, 3.3 or 6.7 Units/kg) on gestation days 6 through 19 or intermittently (13.3 Units/kg on gestation days 6 and 13 only) during organogenesis, no embryofetal data were available at the highest dose administered daily (6.7 Units/kg) because of premature death in all does at that dose. At the lower daily doses or with intermittent dosing, no adverse developmental effects were observed. All dosed for which data were available are less than the MRHD on a body weight basis. In a study in which pregnant rats received 6 weekly intramuscular injections of DYSPORT (4.4, 11.1, 22.2, or 44 Units/kg) beginning on day 6 of gestation and continuing through parturition to weaning, an increase in stillbirths was observed at the highest dose tested, which was maternally toxic. The no-effect dose for pre- and post-natal development toxicity was 22.2 Units/kg (similar to the MRHD).
Pediatric use
8.3 Females and Males of Reproductive Potential Infertility In rats, DYSPORT produced adverse effects on mating behavior and fertility [ see Nonclinical Toxicology (13.1 )].
Geriatric use
8.4 Pediatric Use Cervical Dystonia Safety and effectiveness in pediatric patients have not been established [see Boxed Warning and Warnings and Precautions (5.2) ]. Glabellar Lines DYSPORT is not recommended for use in pediatric patients less than 18 years of age. Spasticity Safety and effectiveness have been established in pediatric patients 2 years of age and older [see Warnings and Precautions (5.1), Adverse Reactions (6.1), and Clinical Studies (14.4)]. The safety and effectiveness of DYSPORT have been established by evidence from adequate and well-controlled studies of DYSPORT in patients 2 years of age and older with upper and lower limb spasticity. The safety and effectiveness of DYSPORT injected into proximal muscles of the lower limb for the treatment of spasticity in pediatric patients has not been established [see Boxed Warning, Warnings and Precautions (5.2), and Adverse Reactions (6.1)]. Safety and effectiveness in pediatric .below the age of 2 years have not been established [see Boxed Warning and Warnings and Precautions (5.2)]. Juvenile Animal Data In a study in which juvenile rats received a single intramuscular injection of DYSPORT (1, 3 or 10 Units/animal) on postnatal day 21, decreased growth and bone length (injected and contralateral limbs), delayed sexual maturation, and decreased fertility were observed at the highest dose tested, which was associated with excessive toxicity during the first week after dosing. In a study in which juvenile rats received weekly intramuscular injections of DYSPORT (0.1, 0.3, or 1.0 Units/animal) from postnatal day 21 to 13 weeks of age, decreases in bone mineral content in the injected limb, associated with atrophy of injected and adjacent muscles, were observed at the highest dose tested. No adverse effects were observed on neurobehavioral development. However, dose levels were not adjusted for growth of the pups. On a body weight basis, the doses at the end of the dosing period were approximately 15% of those at initiation of dosing. Therefore, the effects of DYSPORT throughout postnatal development were not adequately evaluated.
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 [ see Boxed Warning and Warnings and Precautions (5.2) ]. 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 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 https://www.cdc.gov/laboratory/drugservice/index.html .
Description
Botulinum toxin type A, the active ingredient in DYSPORT, is a purified neurotoxin type A complex produced by fermentation of the bacterium Clostridium botulinum 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® (abobotulinumtoxinA) for injection is a sterile, lyophilized powder supplied in a single-dose vial for reconstitution intended for intramuscular injection. Each vial contains 300 Units or 500 Units of lyophilized abobotulinumtoxinA, human serum albumin (125 mcg) and lactose (2.5 mg). DYSPORT may contain trace amounts of cow's milk proteins [ see Contraindications (4) and Warnings and Precautions (5.3) ]. ]. The primary release procedure for DYSPORT uses a cell-based potency assay to determine the potency relative to a reference standard. The assay and reference material are specific to DYSPORT. One unit of DYSPORT corresponds to the calculated median lethal intraperitoneal dose (LD 50 ) in mice. Due to specific details of the assay system, such as vehicle, dilution scheme and laboratory protocols, Units of biological activity of DYSPORT cannot be converted into Units of any other botulinum toxin or any toxin assessed with any other specific assay method.
Mechanism of action
12.1 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.
How supplied
16 HOW SUPPLIED/STORAGE AND HANDLING DYSPORT® (abobotulinumtoxinA) for Injection is a sterile, lyophilized powder supplied in a single-dose, glass vial. Unopened vials of DYSPORT must be stored refrigerated between 2°C to 8°C (36°F to 46°F). Protect from light. 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 carton. If you do not see the hologram, do not use the product. Instead contact 855-463-5127. Cervical Dystonia, Spasticity in Adults, and Pediatric Patients 500 Unit Vial Each vial contains 500 Units of freeze-dried abobotulinumtoxinA. Box containing 1 vial—NDC 15054-0500-1 Box containing 2 vials—NDC 15054-0500-2 300 Unit Vial Each vial contains 300 Units of freeze-dried abobotulinumtoxinA. Box containing 1 vial—NDC 15054-0530-6 Glabellar Lines Each vial contains 300 Units of freeze-dried abobotulinumtoxinA. Box containing 1 vial— NDC 0299-5962-30
Storage
DYSPORT® (abobotulinumtoxinA) for Injection is a sterile, lyophilized powder supplied in a single-dose, glass vial. Unopened vials of DYSPORT must be stored refrigerated between 2°C to 8°C (36°F to 46°F). Protect from light. 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 carton. If you do not see the hologram, do not use the product. Instead contact 855-463-5127.
Patient information
Advise the patient to read the FDA-approved patient labeling (Medication Guide). Swallowing, Speaking, or Breathing Difficulties, or Other Unusual Symptoms 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 [see Warnings and Precautions (5.1, 5.4)]. Dry Eye with the Treatment of Glabellar Lines Inform patients that DYSPORT injection may cause eye dryness [see Warnings and Precautions (5.6)]. Advise patients to report symptoms of eye dryness (e.g., eye pain, eye irritation, photosensitivity, or changes in vision) to their doctor. Ability to Operate Machinery or Vehicles 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.
Label text from the FDA structured product label by Galderma Laboratories, L.P. (revised Oct 24, 2024). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Botulinum Toxin Type A in 3 products
Dysport NDC products (3)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 0299-5962 | Botulinum Toxin Type A 300 U/1 Injection, Powder, Lyophilized, For Solution | Galderma Laboratories, L.P. | BLA |
| 15054-0500 | Botulinum Toxin Type A 500 U/1 Injection, Powder, Lyophilized, For Solution | Ipsen Biopharmaceuticals, Inc. | BLA |
| 15054-0530 | Botulinum Toxin Type A 300 U/1 Injection, Powder, Lyophilized, For Solution | Ipsen Biopharmaceuticals, Inc. | BLA |
Frequently asked questions
What is Dysport used for?
1 INDICATIONS AND USAGE DYSPORT is an acetylcholine release inhibitor and neuromuscular blocking agent indicated for: the treatment of cervical dystonia in adults ( 1.1 ) the temporary improvement in the appearance of moderate to severe glabellar lines associated with procerus and corrugator muscle activity in adults < 65 years of age ( 1.2 ) The treatment of spasticity in patients 2 years of age…
What are the side effects of Dysport?
The following serious adverse reactions are discussed below and elsewhere in labeling: Spread of Toxin Effect [ see Warning s and Precautions (5.1)] Lack of Interchangeability between Botulinum Toxin Products [ see Warnings and Precautions (5.2) ] Hypersensitivity Reactions [ see Warnings and Precautions (5.3) ] Dysphagia and Breathing Difficulties [ see Warnings and Precautions (5.4) ] Facial… See the full label for the complete list.
Who makes Dysport?
Dysport is listed by 2 labelers in the FDA NDC directory, including Galderma Laboratories, L.P., Ipsen Biopharmaceuticals, Inc..