These Highlights Do Not Include All The Information Needed To Use Dysport Safely And Effectively. See Full Prescribing Information For Dysport.

Dose Modification

Where dose modification is necessary for the treatment of cervical dystonia, uncontrolled open-label studies suggest that dose adjustment can be made in 250 Unit steps according to the individual patient's response, with re-treatment every 12 weeks or longer, as necessary, based on return of clinical symptoms. Uncontrolled, open-label studies also suggest that the total dose administered in a single treatment should be between 250 Units and 1000 Units. Re-treatment, if needed, should not occur in intervals of less than 12 weeks. Doses above 1000 Units have not been systematically evaluated.

DYSPORT is a registered trademark of Ipsen Biopharm Limited. Botox, Xeomin and Myobloc are registered trademarks of their respective owners.

© 2023. All rights reserved.

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.

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.

DYSPORT is indicated for the treatment of spasticity in patients 2 years of age and older.

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 (LD₅₀) 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.

Exploratory analyses in trials for glabellar lines in African-American subjects with Fitzpatrick skin types IV, V, or VI and in Hispanic subjects suggested that response rates at Day 30 were comparable to and no worse than the overall population.

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 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.

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).

The following serious adverse reactions are discussed below and elsewhere in labeling:

• Spread of Toxin Effect [see Warnings 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)]

• Concomitant use of DYSPORT and aminoglycosides or other agents interfering with neuromuscular transmission or muscle relaxants, should be observed closely because 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)

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 (see Figure 1).

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 (see Table 16). 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 re-treatment study to assess the safety of multiple treatments.

Treatment with DYSPORT reduced the severity of glabellar lines for up to four months.

Excessive weakness may also be exaggerated by administration of a muscle relaxant before or after administration of DYSPORT.

DYSPORT is indicated for the treatment of cervical dystonia in adults.

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.

Using currently available analytical technology, it is not possible to detect DYSPORT in the peripheral blood following intramuscular injection at the recommended doses.

The efficacy of DYSPORT was evaluated in two randomized, double-blind, placebo-controlled, single-dose, parallel-group studies in treatment-naive 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 of 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^th percentile.

The primary assessment of efficacy 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 Week 4 in both studies (see Table 14).

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 15 indicates the average DYSPORT dose, and percentage of total dose, injected into specific muscles in the pivotal clinical trials.

DYSPORT is an acetylcholine release inhibitor and a 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)

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.

Use of anticholinergic drugs after administration of DYSPORT may potentiate systemic anticholinergic effects such as blurred vision.

• 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)

Postmarketing safety data from DYSPORT and 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 .

Preparation of DYSPORT Solution for Administration (2.2)

• Once reconstituted, store in original container in a refrigerator at 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 Units 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 with 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.

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.

Because adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The following adverse reactions have been identified during post-approval use of DYSPORT: vertigo, photophobia, influenza-like illness, amyotrophy, muscle atrophy, burning sensation, facial paresis, hypoesthesia, erythema, dry eye, and excessive granulation tissue. Hypersensitivity reactions including anaphylaxis have been reported.

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.

The dose of DYSPORT for the treatment of glabellar lines in adults is a total of 50 Units given intramuscularly in five equal aliquots of 10 Units each to achieve clinical effect (see Figure 1).

The clinical effect of DYSPORT may last up to four months. Repeat dosing in clinical studies demonstrated continued efficacy with up to four repeated administrations. It should be administered no 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.

• Administer DYSPORT with care in elderly patients, reflecting the greater frequency of concomitant disease and other drug therapy (8.5)

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.

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.

The recommended initial dose of DYSPORT for the treatment of cervical dystonia in adults is 500 Units given intramuscularly as a divided dose among affected muscles in patients with or without a history of prior treatment with botulinum toxin. (A description of the average DYSPORT dose and percentage of total dose injected into specific muscles in the pivotal clinical trials can be found in Table 15 of Section 14.1, Clinical Studies – Cervical Dystonia.) Limiting the dose injected into the sternocleidomastoid muscle may reduce the occurrence of dysphagia. Clinical studies with DYSPORT in cervical dystonia suggest that the peak effect occurs between two and four weeks after injection. Simultaneous guided injection of DYSPORT with EMG and/or ultrasound may be helpful in locating active muscles.

The possibility of an immune reaction when injected intradermally is unknown. The safety of DYSPORT for the treatment of hyperhidrosis has not been established. DYSPORT is approved only for intramuscular injection.

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Dosing in initial and subsequent treatment sessions should be tailored to the individual based on the size, number and location of muscles involved, severity of spasticity, the presence of local muscle weakness, the patient's response to previous treatment, and/or adverse reaction history with botulinum toxins.

No more than 1 mL should generally be administered at any single injection site. The maximum recommended total dose (upper and lower limb combined) of DYSPORT for the treatment of spasticity in adults is 1500 Units.

Although actual location of the injection sites can be determined by palpation, the use of injection guiding technique (e.g., electromyography, electrical stimulation, or ultrasound) is recommended to target the injection sites.

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.

Postmarketing reports indicate that the effects of DYSPORT and all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. These 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. 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 in approved indications, cases of spread of effect have been reported at doses comparable to or lower than the maximum recommended total dose [see Warnings and Precautions (5.1)].

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)].

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)].

DYSPORT dosing for spasticity in pediatric patients is based on Units per kilogram of body weight. To calculate the total units of DYSPORT required for treatment of one limb, select the dose of DYSPORT in Units/kg and the body weight (kg) of the patient (see Tables 5 and 6). Dosing in initial and sequential treatment sessions should be tailored to the individual patient based on the size, number and location of muscles involved, severity of spasticity, the presence of local muscle weakness, the patient's response to previous treatment, and/or adverse reaction history with botulinum toxins.

No more than 0.5 mL should generally be administered at any single injection site. The maximum recommended total dose of DYSPORT in a single treatment session for spasticity in pediatric patients 2 years and older is 30 Units/kg or 1000 Units in a 3-month interval.

Although actual location of the injection sites can be determined by palpation, the use of injection guiding technique (e.g., electromyography or electrical stimulation, or ultrasound) is recommended to target the injection sites.

Rx only

NDC Number: 15054-0530-6

1 Vial

abobotulinumtoxinA

Dysport^®

for Injection

For intramuscular use

300 units/single-dose vial

WARNING: Dosing units of botulinum toxins are not

interchangeable between commercial products.

Lift here

Rx only

NDC Number: 15054-0500-1

1 Vial

abobotulinumtoxinA

Dysport^®

for Injection

For intramuscular use

500 units/single-dose vial

WARNING: Dosing units of botulinum toxins are not

interchangeable between commercial products.

Lift here

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 ophthalmologist [see Boxed Warning and Warnings and Precautions 5.2].

Caution should be exercised when DYSPORT is used where the targeted muscle shows excessive weakness or atrophy.

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, CJD, or vCJD have ever been identified for licensed albumin or albumin contained in other licensed products.

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).

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. Once reconstituted, unused DYSPORT may be stored in the original container, in a refrigerator at 2°C to 8°C (36°F to 46°F), protected from light for up to 24 hours until time of use. It must be discarded if not used within 24 hours. Do not freeze reconstituted DYSPORT. Discard the vial and needle in accordance with local regulations.

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.

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)].

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.

Dose Modification

Where dose modification is necessary for the treatment of cervical dystonia, uncontrolled open-label studies suggest that dose adjustment can be made in 250 Unit steps according to the individual patient's response, with re-treatment every 12 weeks or longer, as necessary, based on return of clinical symptoms. Uncontrolled, open-label studies also suggest that the total dose administered in a single treatment should be between 250 Units and 1000 Units. Re-treatment, if needed, should not occur in intervals of less than 12 weeks. Doses above 1000 Units have not been systematically evaluated.

DYSPORT is a registered trademark of Ipsen Biopharm Limited. Botox, Xeomin and Myobloc are registered trademarks of their respective owners.

© 2023. All rights reserved.

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.

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.

DYSPORT is indicated for the treatment of spasticity in patients 2 years of age and older.

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 (LD₅₀) 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.

Exploratory analyses in trials for glabellar lines in African-American subjects with Fitzpatrick skin types IV, V, or VI and in Hispanic subjects suggested that response rates at Day 30 were comparable to and no worse than the overall population.

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 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.

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).

The following serious adverse reactions are discussed below and elsewhere in labeling:

• Spread of Toxin Effect [see Warnings 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)]

• Concomitant use of DYSPORT and aminoglycosides or other agents interfering with neuromuscular transmission or muscle relaxants, should be observed closely because 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)

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 (see Figure 1).

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 (see Table 16). 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 re-treatment study to assess the safety of multiple treatments.

Treatment with DYSPORT reduced the severity of glabellar lines for up to four months.

Excessive weakness may also be exaggerated by administration of a muscle relaxant before or after administration of DYSPORT.

DYSPORT is indicated for the treatment of cervical dystonia in adults.

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.

Using currently available analytical technology, it is not possible to detect DYSPORT in the peripheral blood following intramuscular injection at the recommended doses.

The efficacy of DYSPORT was evaluated in two randomized, double-blind, placebo-controlled, single-dose, parallel-group studies in treatment-naive 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 of 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^th percentile.

The primary assessment of efficacy 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 Week 4 in both studies (see Table 14).

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 15 indicates the average DYSPORT dose, and percentage of total dose, injected into specific muscles in the pivotal clinical trials.

DYSPORT is an acetylcholine release inhibitor and a 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)

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.

Use of anticholinergic drugs after administration of DYSPORT may potentiate systemic anticholinergic effects such as blurred vision.

• 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)

Postmarketing safety data from DYSPORT and 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 .

Preparation of DYSPORT Solution for Administration (2.2)

• Once reconstituted, store in original container in a refrigerator at 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 Units 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 with 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.

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.

Because adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The following adverse reactions have been identified during post-approval use of DYSPORT: vertigo, photophobia, influenza-like illness, amyotrophy, muscle atrophy, burning sensation, facial paresis, hypoesthesia, erythema, dry eye, and excessive granulation tissue. Hypersensitivity reactions including anaphylaxis have been reported.

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.

The dose of DYSPORT for the treatment of glabellar lines in adults is a total of 50 Units given intramuscularly in five equal aliquots of 10 Units each to achieve clinical effect (see Figure 1).

The clinical effect of DYSPORT may last up to four months. Repeat dosing in clinical studies demonstrated continued efficacy with up to four repeated administrations. It should be administered no 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.

• Administer DYSPORT with care in elderly patients, reflecting the greater frequency of concomitant disease and other drug therapy (8.5)

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.

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.

The recommended initial dose of DYSPORT for the treatment of cervical dystonia in adults is 500 Units given intramuscularly as a divided dose among affected muscles in patients with or without a history of prior treatment with botulinum toxin. (A description of the average DYSPORT dose and percentage of total dose injected into specific muscles in the pivotal clinical trials can be found in Table 15 of Section 14.1, Clinical Studies – Cervical Dystonia.) Limiting the dose injected into the sternocleidomastoid muscle may reduce the occurrence of dysphagia. Clinical studies with DYSPORT in cervical dystonia suggest that the peak effect occurs between two and four weeks after injection. Simultaneous guided injection of DYSPORT with EMG and/or ultrasound may be helpful in locating active muscles.

The possibility of an immune reaction when injected intradermally is unknown. The safety of DYSPORT for the treatment of hyperhidrosis has not been established. DYSPORT is approved only for intramuscular injection.

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Dosing in initial and subsequent treatment sessions should be tailored to the individual based on the size, number and location of muscles involved, severity of spasticity, the presence of local muscle weakness, the patient's response to previous treatment, and/or adverse reaction history with botulinum toxins.

No more than 1 mL should generally be administered at any single injection site. The maximum recommended total dose (upper and lower limb combined) of DYSPORT for the treatment of spasticity in adults is 1500 Units.

Although actual location of the injection sites can be determined by palpation, the use of injection guiding technique (e.g., electromyography, electrical stimulation, or ultrasound) is recommended to target the injection sites.

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.

Postmarketing reports indicate that the effects of DYSPORT and all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. These 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. 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 in approved indications, cases of spread of effect have been reported at doses comparable to or lower than the maximum recommended total dose [see Warnings and Precautions (5.1)].

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)].

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)].

DYSPORT dosing for spasticity in pediatric patients is based on Units per kilogram of body weight. To calculate the total units of DYSPORT required for treatment of one limb, select the dose of DYSPORT in Units/kg and the body weight (kg) of the patient (see Tables 5 and 6). Dosing in initial and sequential treatment sessions should be tailored to the individual patient based on the size, number and location of muscles involved, severity of spasticity, the presence of local muscle weakness, the patient's response to previous treatment, and/or adverse reaction history with botulinum toxins.

No more than 0.5 mL should generally be administered at any single injection site. The maximum recommended total dose of DYSPORT in a single treatment session for spasticity in pediatric patients 2 years and older is 30 Units/kg or 1000 Units in a 3-month interval.

Although actual location of the injection sites can be determined by palpation, the use of injection guiding technique (e.g., electromyography or electrical stimulation, or ultrasound) is recommended to target the injection sites.

Rx only

NDC Number: 15054-0530-6

1 Vial

abobotulinumtoxinA

Dysport^®

for Injection

For intramuscular use

300 units/single-dose vial

WARNING: Dosing units of botulinum toxins are not

interchangeable between commercial products.

Lift here

Rx only

NDC Number: 15054-0500-1

1 Vial

abobotulinumtoxinA

Dysport^®

for Injection

For intramuscular use

500 units/single-dose vial

WARNING: Dosing units of botulinum toxins are not

interchangeable between commercial products.

Lift here

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 ophthalmologist [see Boxed Warning and Warnings and Precautions 5.2].

Caution should be exercised when DYSPORT is used where the targeted muscle shows excessive weakness or atrophy.

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, CJD, or vCJD have ever been identified for licensed albumin or albumin contained in other licensed products.

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).

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. Once reconstituted, unused DYSPORT may be stored in the original container, in a refrigerator at 2°C to 8°C (36°F to 46°F), protected from light for up to 24 hours until time of use. It must be discarded if not used within 24 hours. Do not freeze reconstituted DYSPORT. Discard the vial and needle in accordance with local regulations.

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.

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)].

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.