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 (Brasinda 2004; Yiannakopoulou 2012).
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) (Heckmann 2001; Naumann 2013; Talarico-Filho 2007). May repeat when clinical effect diminishes. Mean duration of effect ranges from 5.5 months to 8.5 months (Lecouflet 2013).
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 (Ascher 2009; Kassir 2013).
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 (Reddihough 2010; Vashishta 2013).
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 (Hennings 2008; Rapaport 2000). Subsequent doses up to 80 units have been used in order to find the optimum dosage (Slotema 2008). 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.
(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 (Papavasiliou 2013).
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 (Dursun 2019; manufacturer's labeling). 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 (Dabrowski 2018; Delgado 2016; Tilton 2017; manufacturer's labeling). 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 (Dursun 2019).
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.
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.
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
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]
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/125274s115lbl.pdf#page=31, must be dispensed with this medication.
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 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 or electrical stimulation) 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 (de Almeida 2014).
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 (Reddihough 2010; Vashishta 2013).
Parenteral: IM: Spasticity: Use an appropriately sized sterile syringe and needle to administer intramuscularly; 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 or electrical stimulation) is recommended to target the injection sites.
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 fissures; Axillary hyperhidrosis, primary; Lateral canthal lines; Sialorrhea (drooling); Tardive dyskinesia
Botulinum products are not interchangeable; potency differences may exist between the products.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Cervical dystonia:
>10%:
Gastrointestinal: Dysphagia (15% to 39%), xerostomia (13% to 39%)
Local: Discomfort at injection site (13% to 22%)
Nervous system: Voice disorder (6% to 28%), fatigue (12%), headache (11%), facial paresis (5% to 11%)
Neuromuscular & skeletal: Myasthenia (11% to 56%)
Ophthalmic: Eye disease (6% to 17%)
1% to 10%:
Immunologic: Antibody development (binding or neutralizing; 3%)
Local: Pain at injection site (5%)
Nervous system: Dizziness (4%)
Neuromuscular & skeletal: Musculoskeletal pain (7%), amyotrophy (1%)
Respiratory: Dyspnea (3%; onset: ~1 week; duration: ~3 weeks)
Frequency not defined:
Cardiovascular: Decreased heart rate
Endocrine & metabolic: Increased serum glucose
Glabellar lines:
1% to 10%:
Dermatologic: Contact dermatitis (2% to 3%)
Gastrointestinal: Nausea (2%)
Genitourinary: Hematuria (2%)
Infection: Influenza (2% to 3%)
Local: Pain at injection site (3%), discomfort at injection site (2% to 3%), injection site reaction (2% to 3%), swelling at injection site (2% to 3%)
Nervous system: Headache (9%)
Ophthalmic: Blepharoptosis (2%), eyelid edema (2%)
Respiratory: Nasopharyngitis (10%), upper respiratory tract infection (3%), bronchitis (2% to 3%), cough (2% to 3%), pharyngolaryngeal pain (2% to 3%), sinusitis (2%)
Upper limb spasticity:
>10%: Respiratory: Upper respiratory tract infection (children and adolescents: 9% to 11%)
1% to 10%:
Cardiovascular: Hypertension (adults: 1% to 2%), syncope (adults: 1% to 2%)
Dermatologic: Eczema (children and adolescents: <3%; injection site), rash at injection site (children and adolescents: <3%)
Endocrine & metabolic: Increased serum triglycerides (adults: 1% to 2%)
Gastrointestinal: Nausea (children and adolescents: 1% to 3%), constipation (adults: 2%), diarrhea (adults: 1% to 2%)
Hematologic & oncologic: Bruise (adults: 1% to 2%)
Immunologic: Antibody development (4% to 7%; neutralizing: ≤4%)
Infection: Influenza (1% to 3%), infection (adults: 2%)
Local: Bruising at injection site (children and adolescents: <3%), pain at injection site (children and adolescents: <3%), swelling at injection site (children and adolescents: <3%)
Nervous system: Headache (children and adolescents: 3% to 6%; adults: 2%), myasthenia (2% to 6%), epilepsy (2% to 4%), falling (adults: 3%), fatigue (<3%), depression (adults: 2% to 3%), hypoesthesia (adults: 2%), seizure (adults: 2%)
Neuromuscular & skeletal: Limb pain (children and adolescents: <3%), myalgia (children and adolescents: <3%), back pain (adults: 2%), asthenia (adults: 1% to 2%)
Respiratory: Pharyngitis (children and adolescents: 6% to 10%), flu-like symptoms (children and adolescents: <3%), cough (adults: 2%)
Miscellaneous: Accidental injury (adults: 2%)
Frequency not defined: Local: Injection site reaction
Lower limb spasticity:
>10%:
Respiratory: Nasopharyngitis (children and adolescents: 9% to 16%), cough (children and adolescents: 7% to 14%)
Miscellaneous: Fever (children and adolescents: 7% to 12%)
1% to 10%:
Cardiovascular: Peripheral edema (adults: 2%)
Gastrointestinal: Constipation (adults: 2%)
Hepatic: Increased serum alanine aminotransferase (adults: 2%)
Immunologic: Antibody development (4%; neutralizing: ≤2%)
Nervous system: Falling (adults: 6% to 9%), epilepsy (children and adolescents: ≤7%), seizure (children and adolescents: ≤7%), myasthenia (adults: 7%), fatigue (adults: 1% to 4%), headache (adults: 3%), depression (adults: 2% to 3%), insomnia (adults: 2%)
Neuromuscular & skeletal: Limb pain (6% to 7%), arthralgia (adults: 2% to 4%)
Respiratory: Bronchitis (children and adolescents: 7% to 8%), flu-like symptoms (adults: 2%)
Any indication: <1%, postmarketing and/or case reports: Abnormal gait, amyotrophy, anaphylaxis, antibody development, blurred vision, burning sensation, connective tissue disease (excessive granulation tissue), corneal disease, decreased lacrimation, diplopia, disturbance in attention, dry eye syndrome, dysarthria, dysphagia, dyspnea, edema (soft tissue), erythema of skin, facial paresis, feeling abnormal, feeling of heaviness, flu-like symptoms, hypersensitivity reaction, hypertonia, hypoesthesia, photophobia, reduced blinking, respiratory failure, serum sickness, severe dyspnea, urinary incontinence, urticaria, vertigo
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:
• Elderly: 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.
None known.
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.
It is not known if abobotulinumtoxinA is present in breast milk. According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account 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
Solution (reconstituted) (Dysport Intramuscular)
300 unit (per each): $618.60
500 unit (per each): $1,030.80
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