Version May 2024
Postmarketing reports indicate that the effects of 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.
Anal fissure (off-label use): IM: 90 to 150 units in 2 divided doses injected into the internal anal sphincter on each side of the anterior midline (Ref).
Axillary hyperhidrosis, primary (off-label use): Intradermal (off-label route): 100 to 200 units per axilla; injections should be evenly distributed into multiple sites ~1 to 2 cm apart (10 to 20 injections) (Ref). May repeat when clinical effect diminishes. Mean duration of effect ranges from 5.5 months to 8.5 months (Ref).
Cervical dystonia: IM: Initial: 500 units divided among affected muscles in toxin-naïve or toxin-experienced patients. May re-treat at intervals of ≥12 weeks.
Dosage adjustments: Adjust dosage in 250-unit increments; do not administer at intervals <12 weeks; dosage range used in studies: 250 to 1,000 units.
Glabellar lines: Adults <65 years of age: IM: Inject 10 units into each of 5 sites (2 injections in each corrugator muscle and 1 injection in the procerus muscle) for a total dose of 50 units; do not administer at intervals <3 months; efficacy has been demonstrated with up to 4 repeated administrations.
Lateral canthal lines (off-label use): IM: 5 to 15 units injected at 3 sites around each eye for a total dose of 30 to 90 units per treatment, with intervals of ≥3 months between treatments. Refer to published studies for details on injection locations (Ref).
Sialorrhea (off-label use): Intraglandular (Ventral) (off-label route): 15 to 75 units injected per gland (submandibular, parotid or both) either unilaterally or bilaterally with intervals of 4 to 6 months between treatments (Ref).
Spasticity: IM: Individualize dose based on patient size, number and location of muscle involvement, severity of spasticity, local muscle weakness, response to prior treatment, and/or adverse reaction history. May repeat therapy at intervals ≥12 weeks; in clinical studies, the majority of patients were re-treated between 12 to 16 weeks; however, some patients had a longer duration of response (eg, 20 weeks). For upper limb spasticity, total doses of 500 and 1,000 units divided among selected muscles were used in clinical trials. For lower limb spasticity, total doses of 1,000 and 1,500 units divided among selected muscles were used in clinical trials. The maximum recommended total dose (upper and lower limbs combined) is 1,500 units.
Upper limbs:
Brachialis: 200 to 400 units (1 to 2 injections per muscle).
Brachioradialis: 100 to 200 units (1 to 2 injections per muscle).
Biceps brachii: 200 to 400 units (1 to 2 injections per muscle).
Flexor carpi radialis: 100 to 200 units (1 to 2 injections per muscle).
Flexor carpi ulnaris: 100 to 200 units (1 to 2 injections per muscle).
Flexor digitorum profundus: 100 to 200 units (1 to 2 injections per muscle).
Flexor digitorum superficialis: 100 to 200 units (1 to 2 injections per muscle).
Pronator teres: 100 to 200 units (1 injection per muscle).
Lower limbs:
Flexor digitorum longus: 130 to 200 units (1 to 2 injections per muscle).
Flexor hallucis longus: 70 to 200 units (1 injection per muscle).
Gastrocnemius, medial head: 100 to 150 units (1 injection per muscle).
Gastrocnemius, lateral head: 100 to 150 units (1 injection per muscle).
Soleus: 330 to 500 units (3 injections per muscle).
Tibialis posterior: 200 to 300 units (2 injections per muscle).
Tardive dyskinesia (off-label use): IM: 20 to 50 units injected per site (total dosage range: 80 to 100 units). Dose, duration, and number of injections are dependent on muscle size and severity (Ref). Subsequent doses up to 80 units have been used in order to find the optimum dosage (Ref). Additional data may be necessary to further define the role of abobotulinumtoxinA in the treatment of this condition.
There are no dosage adjustments provided in the manufacturer's labeling; however, dosage adjustment unlikely as abobotulinumtoxinA is not expected to be present in peripheral blood at recommended doses following IM injection.
There are no dosage adjustments provided in the manufacturer's labeling; however, dosage adjustment unlikely as abobotulinumtoxinA is not expected to be present in peripheral blood at recommended doses following IM injection.
Cervical dystonia: Refer to adult dosing. No specific adjustment recommended.
Glabellar lines: Not recommended in patients ≥65 years of age.
Spasticity: Refer to adult dosing.
(For additional information see "AbobotulinumtoxinA (Dysport): Pediatric drug information")
Note: Potency units are specific to product and assay method utilized; do not interchange botulinum toxin products.
Spasticity: Note: Individualize dose based on the following: Patient size, number and location of muscles involved, severity of spasticity, local muscle weakness, response to prior treatment, and/or adverse reaction history. The lowest recommended dose should be used when initiating treatment (regardless of indication). In a 3-month interval, the maximum total dose is 30 units/kg or 1,000 units, whichever is less; however, a higher maximum total dose of 1,500 units per treatment cycle has been utilized in more severe cases with a positive safety profile (Ref).
Lower extremity:
Children ≥2 years and Adolescents <18 years: IM: 10 to 15 units/kg per limb; reported total dose range: 5 to 30 units/kg; for unilateral limb injections, the maximum total dose per treatment session: 15 units/kg or 1,000 units, whichever is less; for bilateral limb injections, the maximum total dose per treatment session: 30 units/kg or 1,000 units, whichever is less (Ref). May repeat therapy at intervals ≥12 weeks; in clinical studies, the majority of patients were re-treated between 16 to 22 weeks; however, some patients had a longer duration of response.
The majority of efficacy trials evaluated equinus foot and the following individual dose-range per muscle per limb are recommended (Ref). Refer to prescribing information for specific diagrams of recommended injection sites:
|
Muscle |
Total Dosage Per Muscle |
Number of Sites Per Muscle |
|---|---|---|
|
Gastrocnemius |
6 to 9 units/kg |
1 to 4 sites |
|
Soleus |
4 to 6 units/kg |
1 to 2 sites |
|
Total |
10 to 15 units/kg divided across both muscles |
1 to 6 sites |
In an open-label continuation phase trial evaluating patients after the first 4 treatment cycles, titration of the total dose of abobotulinumtoxinA in 5 unit/kg increments based on clinical response for combined lower and upper limb spasticity was described; injections were administered in other muscles groups as appropriate including hamstrings, tibialis posterior, hip adductors, iliopsoas, or upper limb muscle groups; maximum dose per treatment cycle: 30 units/kg or 1,000 units, whichever was less (Ref).
Upper extremity:
Children ≥2 years weighing ≥10 kg and Adolescents: IM: Total dose: 8 units/kg or 16 units/kg per session divided amongst targeted muscles; maximum total dose per session: 16 units/kg not to exceed 640 units. May repeat therapy when effect of previous treatment diminishes but no sooner than 16 weeks from previous administration; in clinical trials, the usual range was 16 to 28 weeks; however, some patients experienced therapeutic effects for a longer duration (eg, ≥34 weeks after treatment).
The following individual dose range per muscle per limb are suggested. Refer to prescribing information for specific diagrams of recommended injection sites.
|
Muscle |
Recommended Dose Range Per Muscle Per Upper Limb |
Number of Injection Sites Per Muscle |
|---|---|---|
|
Brachialis |
3 to 6 units/kg |
Up to 2 sites |
|
Brachioradialis |
1.5 to 3 units/kg |
1 site |
|
Biceps brachii |
3 to 6 units/kg |
Up to 2 sites |
|
Flexor carpi radialis (FCR) |
2 to 4 units/kg |
Up to 2 sites |
|
Flexor carpi ulnaris (FCU) |
1.5 to 3 units/kg |
1 site |
|
Flexor digitorum profundus (FDP) |
1 to 2 units/kg |
1 site |
|
Flexor digitorum superficialis (FDS) |
1.5 to 3 units/kg |
Up to 4 sites |
|
Pronator quadratus |
0.5 to 1 units/kg |
1 site |
|
Pronator teres |
1 to 2 units/kg |
1 site |
|
Total dose |
8 to 16 units/kg not to exceed 640 units | |
There are no dosage adjustments provided in the manufacturer's labeling; however, dosage adjustment unlikely as abobotulinumtoxinA is not expected to be present in peripheral blood at recommended doses following IM injection.
There are no dosage adjustments provided in the manufacturer's labeling; however, dosage adjustment unlikely as abobotulinumtoxinA is not expected to be present in peripheral blood at recommended doses following IM injection.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults unless otherwise indicated.
Cervical dystonia:
>10%:
Gastrointestinal: Dysphagia (15% to 39%), xerostomia (13% to 39%)
Local: Discomfort at injection site (13% to 22%)
Nervous system: Facial paresis (5% to 11%), fatigue (12%), headache (11%), myasthenia (11% to 56%), voice disorder (6% to 28%)
Ophthalmic: Ophthalmic signs and symptoms (6% to 17%; including accommodation disturbance, blurred vision, decreased visual acuity, diplopia, dry eye syndrome, eye pain, eye pruritus, eyelid disease)
1% to 10%:
Immunologic: Antibody development (binding or neutralizing: 3%)
Local: Pain at injection site (5%)
Nervous system: Dizziness (4%)
Neuromuscular & skeletal: Amyotrophy (1%), musculoskeletal pain (7%)
Respiratory: Dyspnea (3%)
Frequency not defined:
Cardiovascular: Decreased heart rate
Endocrine & metabolic: Increased serum glucose
Nervous system: Disturbance in attention
Glabellar lines:
1% to 10%:
Dermatologic: Contact dermatitis (2% to 3%)
Gastrointestinal: Nausea (2%)
Genitourinary: Hematuria (2%)
Infection: Influenza (2% to 3%)
Local: Injection-site reaction (3%; including discomfort at injection site [2% to 3%], pain at injection site [3%], swelling at injection site [2% to 3%])
Nervous system: Headache (9%)
Ophthalmic: Blepharoptosis (2%), eyelid edema (2%)
Respiratory: Bronchitis (2% to 3%), cough (2% to 3%), nasopharyngitis (10%), pharyngolaryngeal pain (2% to 3%), sinusitis (2%), upper respiratory tract infection (3%)
<1%: Immunologic: Antibody development
Upper limb spasticity:
>10%: Respiratory: Upper respiratory tract infection (children and adolescents: 9% to 11%)
1% to 10%:
Cardiovascular: Hypertension (1% to 2%), syncope (1% to 2%)
Endocrine & metabolic: Increased serum triglycerides (1% to 2%)
Gastrointestinal: Constipation (2%), diarrhea (1% to 2%), nausea (children and adolescents: 1% to 3%)
Hematologic & oncologic: Bruise (1% to 2%)
Immunologic: Antibody development (7%; neutralizing: 4%)
Infection: Infection (2%), influenza (children, adolescents, and adults: 1% to 3%)
Local: Bruising at injection site (children and adolescents: <3%), pain at injection site (children and adolescents: <3%), rash at injection site (including eczema; children and adolescents: <3%), swelling at injection site (children and adolescents: <3%)
Nervous system: Asthenia (1% to 2%), depression (2% to 3%), falling (3%), fatigue (children, adolescents, and adults: <3%), headache (children, adolescents, and adults: 2% to 6%), hypoesthesia (2%), myasthenia (children, adolescents, and adults: 2% to 6%), seizure (children, adolescents, and adults: 2% to 4%)
Neuromuscular & skeletal: Back pain (2%), limb pain (children, adolescents, and adults: <3%), myalgia (children and adolescents: <3%)
Respiratory: Cough (2%), flu-like symptoms (children and adolescents: <3%), pharyngitis (children and adolescents: 6% to 10%)
Miscellaneous: Accidental injury (2%)
<1%:
Gastrointestinal: Dysphagia
Nervous system: Abnormal gait, feeling of heaviness, hypertonia
Frequency not defined: Local: Injection-site reaction
Lower limb spasticity:
>10%:
Respiratory: Cough (children and adolescents: 7% to 14%), nasopharyngitis (children and adolescents: 9% to 16%)
Miscellaneous: Fever (children and adolescents: 7% to 12%)
1% to 10%:
Cardiovascular: Peripheral edema (2%)
Gastrointestinal: Constipation (2%)
Hepatic: Increased serum alanine aminotransferase (2%)
Immunologic: Antibody development (children and adolescents: neutralizing: 2%; adults: <1% [neutralizing: 1%])
Nervous system: Depression (2% to 3%), falling (6% to 9%), fatigue (1% to 4%), headache (3%), insomnia (2%), myasthenia (7%), seizure (children and adolescents: 4% to 7%)
Neuromuscular & skeletal: Arthralgia (2% to 4%), limb pain (children, adolescents, and adults: 6% to 7%)
Respiratory: Bronchitis (children and adolescents: 7% to 8%), flu-like symptoms (2%)
Any indication:
Postmarketing:
Dermatologic: Erythema of skin
Hypersensitivity: Hypersensitivity reaction (including anaphylaxis), serum sickness
Nervous system: Burning sensation, facial paresis, vertigo
Neuromuscular & skeletal: Connective tissue disease (excessive granulation tissue)
Ophthalmic: Photophobia
Miscellaneous: Iatrogenic botulism
Known hypersensitivity (eg, anaphylaxis) to botulinum toxin or any component of the formulation, including cow milk protein; infection at the proposed injection site(s)
Concerns related to adverse effects:
• Anaphylaxis/hypersensitivity reactions: Serious hypersensitivity (eg, serum sickness, urticaria, soft tissue edema, dyspnea) and anaphylactic reactions may occur rarely; immediate treatment (including epinephrine 1 mg/mL) should be available.
• Antibody formation: Higher doses or more frequent administration may result in neutralizing antibody formation and loss of efficacy.
• Cardiovascular events: Rarely, arrhythmia and myocardial infarction have been reported with use of onabotulinumtoxinA (another botulinum toxin formulation), sometimes in patients with preexisting cardiovascular disease.
• Dysphagia: Common when used for cervical dystonia and may persist for several weeks after administration. In severe cases, patients may require alternative feeding methods (eg, feeding tube). Risk factors include smaller neck muscle mass, bilateral injections into the sternocleidomastoid muscle, or injections into the levator scapulae. Risk of aspiration resulting from severe dysphagia is increased in patients when swallowing is already compromised. Limiting the dose injected into the sternocleidomastoid muscle may reduce the occurrence of dysphagia.
• Ophthalmic: Dry eye, reduced tear production, reduced blinking, and corneal disorders may occur when treating glabellar lines; persistent symptoms may require ophthalmologic evaluation.
• Systemic toxicity: Distant spread of botulinum toxin beyond the site of injection has been reported. Immediate medical attention required if respiratory, speech, or swallowing difficulties appear.
Disease-related concerns:
• Neuromuscular disease: Avoid use in patients with myasthenia gravis (AAN [Narayanaswami 2021]). Use with caution in patients with peripheral motor neuropathic disease, amyotrophic lateral sclerosis, or neuromuscular junction disorders (eg, Lambert-Eaton syndrome).
• Respiratory disease: Use extreme caution in patients with preexisting respiratory disease; treatment of cervical dystonia using botulinum toxin may weaken accessory muscles that are necessary for these patients to maintain adequate ventilation. Serious breathing difficulties, including respiratory failure, have been reported. Risk of aspiration resulting from severe dysphagia is increased in patients with decreased respiratory function.
Dosage form specific issues:
• Albumin: Product contains albumin and may carry a remote risk for transmission of viral diseases and variant Creutzfeldt-Jakob disease.
• Lactose: Product may contain lactose; do not administer to patients allergic to cow's milk protein.
• Product interchangeability: Botulinum products (abobotulinumtoxinA, onabotulinumtoxinA, rimabotulinumtoxinB) are not interchangeable; potency units are specific to each preparation and cannot be compared or converted to any other botulinum product.
Special populations:
• Older adult: Temporary reduction in glabellar lines: Efficacy was not observed in older adults (≥65 years of age) and an increased frequency of ocular adverse events was reported in older adults compared to younger adults.
Other warnings/precautions:
• Chronic therapy: Long-term effects of chronic therapy unknown.
• Injection site: Use with caution if there is inflammation or excessive weakness or atrophy at the proposed injection site(s); use is contraindicated if infection is present.
• Temporary reduction in glabellar lines: Appropriate use: Do not use more frequently than every 3 months. Patients with marked facial asymmetry, ptosis, excessive dermatochalasis, deep dermal scarring, thick sebaceous skin, or the inability to substantially lessen glabellar lines by physically spreading them apart were excluded from clinical trials. Use with caution in patients with surgical alterations to the facial anatomy. Reduced blinking from injection of the orbicularis muscle can lead to corneal exposure and ulceration. Spatial disorientation, double vision, or past pointing may occur if one or more extraocular muscles are paralyzed.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intramuscular:
Dysport: 300 units (1 ea); 500 units (1 ea) [contains albumin human, lactose monohydrate, milk protein]
No
Solution (reconstituted) (Dysport Intramuscular)
300 unit (per each): $618.60
500 unit (per each): $1,030.80
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intramuscular:
Dysport Aesthetic: 300 units (1 ea) [contains albumin human, milk protein]
Dysport Therapeutic: 300 units (1 ea); 500 units (1 ea) [contains albumin human, milk protein]
IM:
Cervical dystonia: Use an appropriately sized needle to administer intramuscularly. Limiting the dose injected into the sternocleidomastoid muscle may reduce the occurrence of dysphagia. Simultaneous EMG-guided application and/or ultrasound may be helpful in locating active muscle not identified by physical examination alone.
Glabellar lines: Use an appropriately sized needle to administer intramuscularly. Apply pressure on the superior medial orbital rim, and inject into each of 5 sites (2 injections in each corrugator muscle and 1 in the procerus muscle). Ensure injected volume/dose is accurate and where feasible keep to a minimum. Avoid injection near the levator palpebrae superioris, particularly in patients with larger brow depressor complexes. Medial corrugator injections should be at least 1 cm above the bony supraorbital ridge. Do not inject toxin closer than 1 cm above the central eyebrow.
Spasticity (upper or lower limb): Use an appropriately sized needle to administer intramuscularly. Although actual location of the injection sites can be determined by palpation, the use of an injection guiding technique (eg, electromyography, electrical stimulation, ultrasound) is recommended to target the injection sites. Do not administer >1 mL (upper or lower limb spasticity) in any single injection site.
Intradermal (off label): Primary axillary hyperhidrosis (off-label use): Use a 30-gauge needle to administer intradermally in the axillae. Prior to administration, injection area should be defined by standard staining techniques such as Minor's Iodine-Starch Test because the axillary hyperhidrotic area may not coincide with the hairy underarm region (Ref).
Intraglandular (off label): Sialorrhea (off-label use): Inject into the submandibular and/or parotid gland either unilaterally or bilaterally. Ultrasound guidance is recommended to ensure delivery into the submandibular gland and is advisable for the parotids; however, experienced clinicians have relied on landmarks for the parotids (Ref).
Parenteral: IM: Spasticity: Use an appropriately sized sterile syringe and needle to administer IM; the maximum volume of any injection site is 0.5 mL. Although actual location of the injection sites can be determined by palpation, the use of an injection-guiding technique (eg, electromyography, electrical stimulation, or ultrasound) is recommended to target the injection sites.
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/125274s123lbl.pdf#page=30, must be dispensed with this medication.
Cervical dystonia: Treatment of adults with cervical dystonia.
Glabellar lines: Temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and procerus muscle activity in adults <65 years of age.
Spasticity: Treatment of spasticity in patients ≥2 years of age.
Anal fissure; Axillary hyperhidrosis, primary; Lateral canthal lines; Sialorrhea (drooling); Tardive dyskinesia
Botulinum products are not interchangeable; potency differences may exist between the products.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Aminoglycosides: May enhance the neuromuscular-blocking effect of Botulinum Toxin-Containing Products. Risk C: Monitor therapy
Anticholinergic Agents: Botulinum Toxin-Containing Products may enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Botulinum Toxin-Containing Products: May enhance the neuromuscular-blocking effect of other Botulinum Toxin-Containing Products. Risk C: Monitor therapy
Muscle Relaxants (Centrally Acting): May enhance the adverse/toxic effect of Botulinum Toxin-Containing Products. Specifically, the risk for increased muscle weakness may be enhanced. Risk C: Monitor therapy
Neuromuscular-Blocking Agents: Botulinum Toxin-Containing Products may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Adverse events have been observed in animal reproduction studies.
Outcome data following maternal use of abobotulinumtoxinA during pregnancy are limited (Cohen 2017).
Because data related to the use of botulinum toxins for indications such as cervical dystonia and cosmetic procedures during pregnancy are limited, use is generally avoided (Contarino 2017; Garg 2022; Morgan 2006; Trivedi 2017).
It is not known if abobotulinumtoxinA is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother
Contains lactose; patients allergic to cow's milk protein should not receive product.
AbobotulinumtoxinA (previously known as botulinum toxin type A) is a neurotoxin produced by Clostridium botulinum, spore-forming anaerobic bacillus, which appears to affect only the presynaptic membrane of the neuromuscular junction in humans, where it prevents calcium-dependent release of acetylcholine and produces a state of denervation. Muscle inactivation persists until new fibrils grow from the nerve and form junction plates on new areas of the muscle-cell walls.
Onset of action: Peak effect: Cervical dystonia: 2 to 4 weeks; Upper limb spasticity: 1 week
Duration: Cervical dystonia, glabellar lines: ≥4 months; Lower limb spasticity: ≥5 ½ months; Upper limb spasticity: ≥5 months
Absorption: Not expected to be present in peripheral blood at recommended doses following intramuscular (IM) injection
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