AbobotulinumtoxinA (Monograph)

Brand name: Dysport
Drug class: Botulinum toxins
Chemical name: Complex with hemagglutinin (Clostridium botulinum A strain Hall) and neurotoxin (Clostridium botulinum A strain Hall light chain) and protein NTNH (non-toxin non-hemagglutinin) (Clostridium botulinum A strain Hall) neurotoxin (Clostridium botulinum A strain Hall heavy chain)
CAS number: 953397-35-8

Medically reviewed by Drugs.com on Sep 21, 2023. Written by ASHP.

Introduction

Neurotoxin produced by Clostridium botulinum; disrupts neurotransmission by inhibiting release of acetylcholine from peripheral cholinergic and ganglionic autonomic nerve terminals.

Uses for AbobotulinumtoxinA

Currently, 3 botulinum toxin type A preparations (abobotulinumtoxinA [Dysport], incobotulinumtoxinA [Xeomin], and onabotulinumtoxinA [Botox, Botox Cosmetic]) and one botulinum toxin type B preparation (rimabotulinumtoxinB [Myobloc]) are commercially available in the US. These preparations are not interchangeable; assay methods used to determine potency of botulinum toxins are specific to each individual manufacturer and/or formulation.

Cervical Dystonia

Treatment of cervical dystonia (spasmodic torticollis) in adults to decrease severity of abnormal head position and neck pain; designated an orphan drug by FDA for this use.

Botulinum toxins considered first-line therapy for cervical dystonia. AbobotulinumtoxinA shown to produce objective and subjective improvements in functional impairment and/or disability. Evidence supporting use largely based on clinical trials of short duration using single injection cycles; additional studies needed to establish long-term efficacy and safety, optimum treatment intervals, and administration techniques (e.g., use of electromyogram [EMG] guidance versus palpation).

Glabellar Facial Lines

Temporary improvement in appearance of moderate to severe glabellar facial (“frown”) lines associated with corrugator and/or procerus muscle activity in adults <65 years of age.

Temporarily weakens corrugator and procerus muscle complex, reducing generation of expression-related glabellar facial lines.

Spasticity in Adults

Treatment of spasticity (e.g., upper or lower limb) in adults. Safety and efficacy based on studies in adults who experienced a stroke or traumatic brain injury ≥6 months previously.

Decreases spasticity and improves muscle tone and range of motion in upper limbs in adults with traumatic brain injury- or stroke-related spasticity; also improves muscle tone in lower limbs in such patients.

The American Academy of Neurology (AAN) recommends therapy with a botulinum toxin for the treatment of focal manifestations spasticity involving upper limbs in adults.

Lower Limb Spasticity in Pediatric Patients

Treatment of lower limb spasticity in pediatric patients ≥2 years of age. Safety and efficacy based on studies in pediatric patients with dynamic equinus foot deformity associated with cerebral palsy.

AAN states that botulinum toxin type A should be considered an effective and generally well-tolerated treatment for localized (one extremity)/segmental (lower body, hemibody) spasticity in children and adolescents with cerebral palsy.

Designated orphan drug by FDA for treatment of dynamic muscle contractures in children and adolescents with cerebral palsy^{† [off-label]}.

Blepharospasm

Has been used for the treatment of essential blepharospasm^{† [off-label]}. Designated an orphan drug by FDA for this use.

AAN states that a botulinum toxin should be considered for the treatment of blepharospasm.

Related/similar drugs

Botox, onabotulinumtoxinA, tazarotene topical, Xeomin, Dysport, Botox Cosmetic, Daxxify

AbobotulinumtoxinA Dosage and Administration

General

• Individualize dosage according to patient response and particular condition treated.

• Do not exceed recommended dose and frequency; excessive and/or unintended neuromuscular weakness may occur if higher than recommended dosages are given. Use minimum effective dosage whenever possible to reduce risk of adverse effects.

Administration

IM Administration

Administer by IM injection into affected muscles.

Instructions for reconstitution and administration are specific to each vial size and condition being treated; consult manufacturer's labeling for detailed instructions regarding reconstitution, preparation, and administration.

Monitor patients for respiratory distress or other possible adverse effects related to spread of botulinum toxin (e.g., dysphagia, dysphonia, unexpected muscle weakness, urinary incontinence, ptosis, double vision, blurred vision, dysarthria). (See Distant Spread of Toxin Effects under Cautions.)

Reconstitution

For cervical dystonia, reconstitute vial labeled as containing 300 or 500 units of lyophilized drug with 0.6 or 1 mL of preservative-free 0.9% sodium chloride injection to provide a solution containing 50 units per 0.1 mL (or 500 units per mL), respectively. Alternatively, reconstitute a vial labeled as containing 500 units of the drug with 2 mL of preservative-free 0.9% sodium chloride injection to provide a solution containing 25 units per 0.1 mL (or 250 units per mL).

For glabellar facial lines, reconstitute a vial labeled as containing 300 units of lyophilized drug with 1.5 or 2.5 mL of preservative-free 0.9% sodium chloride injection to provide a solution containing 10 units per 0.05 mL (or 20 units per 0.1 mL) or 10 units per 0.08 mL (or 12 units per 0.1 mL), respectively.

For the treatment of upper or lower limb spasticity in adults, reconstitute a vial labeled as containing 300 or 500 units of lyophilized drug with 1.5 or 2.5 mL, respectively, of preservative-free 0.9% sodium chloride injection to provide a solution containing 20 units per 0.1 mL (or 200 units per mL). Alternatively, reconstitute a vial labeled as containing 300 or 500 units of lyophilized drug with 3 or 5 mL of preservative-free 0.9% sodium chloride injection, respectively, to provide a solution containing 10 units per 0.1 mL (or 100 units per mL).

For the treatment of lower limb spasticity in pediatric patients, reconstitute a vial labeled as containing 300 or 500 units of lyophilized drug with 1.5 or 2.5 mL, respectively, of preservative-free 0.9% sodium chloride injection, to provide a solution containing 20 units per 0.1 mL (or 200 units per mL). Further dilution with preservative-free 0.9% sodium chloride injection may be required to achieve the final volume for injection.

Use appropriately sized needle to draw the required amount of diluent into a syringe. Insert needle into drug vial and allow partial vacuum to draw in diluent; do not use vial if vacuum is absent. Gently rotate vial until lyophilized drug is completely dissolved.

If vial labeled as containing 500 units of abobotulinumtoxinA is being reconstituted with 5 mL of diluent, add diluent in 2 steps. First, reconstitute vial labeled as containing 500 units of drug by adding 2.5 mL of preservative-free 0.9% sodium chloride injection and gently swirling. Then, without inverting vial, withdraw reconstituted solution from vial into a 5-mL syringe containing an additional 2.5 mL of preservative-free 0.9% sodium chloride injection. Gently mix in syringe.

Use reconstituted solutions immediately if reconstituted in syringe, or store in original container at 2–8°C for up to 24 hours. Carefully discard any unused portions as medical waste.

Injection Techniques (Cervical Dystonia)

Administer total dose per treatment session as several injections divided among affected muscles. Use a sterile 23- or 25-gauge needle.

EMG-guided injections may be helpful in locating target injection sites, particularly for muscles that are difficult to identify by physical examination alone.

Injection Techniques (Glabellar Facial Lines)

Identify injection sites by palpating for areas of tense muscle mass in the lateral corrugator and vertical procerus muscles while patient is frowning; location, size, and use of such muscles may vary considerably among individuals.

Administer using a 30-gauge needle. Apply digital pressure to superior medial orbital rim while injecting through skin.

Injections into the medial corrugator muscle should be ≥1 cm above the supraorbital ridge and should not be injected <1 cm above the central eyebrow.

Avoid injections near the levator palpebrae superioris, especially in individuals with larger brow-depressor complexes.

Injection Techniques (Spasticity in Adults)

Administer total dose per treatment session as several injections divided among affected muscles of upper or lower limbs.

Can identify injection sites by palpation; however, use of injection-guiding techniques (e.g., EMG, electrical stimulation) recommended.

Injection Techniques (Lower Limb Spasticity in Pediatric Patients)

Pediatric patients ≥2 years of age: Administer total dose per treatment session as several injections divided among affected muscles. When possible, distribute dose across >1 injection site in any single muscle (see Table 1).

Can identify injection sites by palpation; however, use of injection-guiding techniques (e.g., EMG, electrical stimulation) recommended.

Dosage

Potency of abobotulinumtoxinA expressed in units of biologic activity; each unit is equivalent to the median intraperitoneal lethal dose (LD₅₀) in mice.

Assay methods used to determine potency of various botulinum toxin preparations are specific to each individual preparation; units of biologic activity of abobotulinumtoxinA cannot be compared with or converted to units of other botulinum toxin preparations.

Pediatric Patients

Lower Limb Spasticity

IM

Pediatric patients ≥2 years of age: Manufacturer-recommended doses and muscles to be injected shown in Table 1.

^*Do not exceed a total dose of 15 units/kg (for unilateral injection) or 30 units/kg (for bilateral injections) or 1000 units, whichever is less.

Recommended total abobotulinumtoxinA dose per treatment session is 10–15 units/kg for unilateral lower limb injections or 20–30 units/kg for bilateral lower limb injections.

Individualize doses in initial and sequential treatment sessions based on the size, number, and location of muscles involved; severity of spasticity; presence of local muscle weakness; patient response to previous treatment; and history of adverse events with botulinum toxin preparations.

Use of injection-guiding techniques (e.g., EMG, electrical stimulation) to guide injections recommended.

Divide total dose among the affected spastic muscles of the lower limb(s). Distribute dose across more than 1 injection site in any single muscle when possible (see Table 1). Administer no more than 0.5 mL of the drug at any single injection site.

May repeat treatment when effect of previous injection has diminished, but no sooner than 12 weeks after previous injection. Degree and pattern of muscle spasticity at time of reinjection may require alterations in dose and muscles to be injected.

Adults

Cervical Dystonia

IM

Toxin-naive and previously treated patients: Initially, 500 units as a divided dose among affected muscles.

In clinical studies, median initial doses injected into the sternocleidomastoid, splenius capitis, trapezius, levator scapulae, scalenus (medius and anterior), semispinalis capitis, and longissimus muscles were 125 units (range 50–350), 200 units (range 75–450), 102.6 units (range 50–300), 105.3 units (range 50–200), 115.5 units (range 50–300), 131.6 units (range 50–250), and 150 units (range 100–200), respectively.

Adjust total dosage administered in subsequent treatment sessions by increments of 250 units based on patient response.

Usual duration of response 12–16 weeks or longer; may repeat treatments every 12–16 weeks or longer if symptoms return.

Glabellar Facial Lines

IM

Manufacturer recommends a total dose of 50 units per treatment session, administered as 10 units (0.05 or 0.08 mL depending on concentration of reconstituted solution) into each of 5 sites: 2 in each corrugator muscle and one in procerus muscle.

Cosmetic effects usually persist for up to 4 months. May repeat treatments at intervals of ≥3 months.

Variable dosing based on gender and muscle mass also has been used in clinical practice. Higher doses generally recommended in men versus women due to greater muscle mass in men.

Spasticity (Upper Limb)

IM

Manufacturer-recommended doses and muscles to be injected shown in Table 2.

Individualize doses in initial and sequential treatment sessions based on the size, number, and location of muscles involved; severity of spasticity; presence of local muscle weakness; patient response to previous treatment; and history of adverse events with botulinum toxin preparations.

Use of injection-guiding techniques (e.g., EMG, electrical stimulation) to guide injections recommended.

Doses of 500 or 1000 units divided among selected muscles at a given treatment session used in clinical trials.

Administer no more than 1 mL of the drug at any single injection site.

May expect clinical improvement one week after administration of abobotulinumtoxinA. May repeat treatment when effect of previous injection has diminished, but generally no sooner than 12 weeks after previous injection. Degree and pattern of muscle spasticity at time of reinjection may require alterations in dose and muscles to be injected.

Spasticity (Lower Limb)

IM

Manufacturer-recommended doses and muscles to be injected shown in Table 3.

Individualize doses in initial and sequential treatment sessions based on the size, number, and location of muscles involved; severity of spasticity; presence of local muscle weakness; patient response to previous treatment; and history of adverse events with botulinum toxin preparations.

Use of injection-guiding techniques (e.g., EMG, electrical stimulation) to guide injections recommended.

Doses of 1000 or 1500 units divided among selected muscles at a given treatment session used in clinical trials.

Administer no more than 1 mL of the drug at any single injection site.

May repeat treatment when effect of previous injection has diminished, but generally no sooner than 12 weeks after previous injection. Degree and pattern of muscle spasticity at time of reinjection may require alterations in dose and muscles to be injected.

Prescribing Limits

Pediatric Patients

Lower Limb Spasticity

IM

Pediatric patients ≥2 years of age: 15 units/kg for unilateral lower limb injections or 30 units/kg for bilateral lower limb injections. Do not exceed 1000 units per treatment session.

Do not repeat treatments more frequently than once every 12 weeks.

Adults

Cervical Dystonia

IM

Dosage range was 250–1000 units per single treatment session in uncontrolled, open-label clinical studies; safety and efficacy of doses >1000 units not established.

Limit total dose injected into sternocleidomastoid muscle to minimize risk of dysphagia. (See Dysphagia/Breathing Difficulties under Cautions.)

Do not repeat treatments more frequently than once every 12 weeks.

Glabellar Facial Lines

IM

Do not repeat treatments more frequently than once every 3 months.

Spasticity (Upper or Lower Limb)

IM

Maximum recommended total dose (upper and lower limb combined) of abobotulinumtoxinA is 1500 units.

Do not repeat treatments more frequently than once every 12 weeks.

Special Populations

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy. (See Geriatric Use under Cautions.)

Cautions for AbobotulinumtoxinA

Contraindications

• Known hypersensitivity to any botulinum toxin preparation or any ingredient in their formulations.

• Allergy to cow milk protein.

• Infection at proposed injection site(s).

Warnings/Precautions

Warnings

Distant Spread of Toxin Effects

In some cases, toxin effects may be observed beyond local sites of injection. (See Boxed Warning.)

Serious adverse effects consistent with mechanism of botulinum toxin action (e.g., asthenia, generalized muscle weakness, diplopia, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence, breathing difficulties) reported. (See Advice to Patients.)

In some cases, severe swallowing and breathing difficulties required hospitalization, mechanical ventilation, or feeding tubes and/or resulted in death. (See Dysphagia/Breathing Difficulties under Cautions.)

Risk of toxin spread probably highest in children treated for spasticity.

Sensitivity Reactions

Hypersensitivity Reactions

Potential risk of hypersensitivity. (See Contraindications under Cautions.) Serious hypersensitivity reactions (including anaphylaxis) reported rarely with another preparation of botulinum toxin type A (Botox).

Intradermal Sensitivity

Possibility of immune reaction following intradermal administration of abobotulinumtoxinA not known. Manufacturer states that safety and efficacy of abobotulinumtoxinA for treatment of hyperhidrosis not established.

Other Warnings/Precautions

Lack of Interchangeability Among Botulinum Toxin Preparations

The method used to determine potency (“units”) of abobotulinumtoxinA is specific to the Dysport preparation; therefore, units of biologic activity for abobotulinumtoxinA cannot be compared with or converted to units of any other botulinum toxin preparation.

Dysphagia/Breathing Difficulties

Risk of dysphagia in patients receiving a botulinum toxin for cervical dystonia. Usually a consequence of cervical muscle weakening from local areas of injection, but also may be related to distant spread of toxin effects. (See Distant Spread of Toxin Effects under Cautions.)

Botulinum toxins may weaken neck muscles that serve as accessory muscles of ventilation, resulting in critical loss of breathing capacity in patients with respiratory disorders. Aspiration and death reported as a complication of severe dysphagia. Patients with compromised swallowing function are at increased risk of aspiration.

Immediate medical attention may be required if sudden difficulties in speech or swallowing develop during or following treatment; such effects may occur hours to weeks after injection. Gastric feeding tubes may be required in severe cases.

Administration Precautions in Patients with Glabellar Facial Lines

Administer with caution in patients with surgically altered facial anatomy, excessive weakness or atrophy in target muscles, marked facial asymmetry, inflammation, ptosis, excessive dermatochalasis, deep dermal scarring, thick sebaceous skin, or glabellar lines that cannot be substantially decreased manually.

Clinicians who administer abobotulinumtoxinA should understand the relevant neuromuscular and/or orbital anatomy of the therapeutic area and effects of any changes from surgical alterations.

Increased incidence of ptosis observed with use of higher than recommended dosages; do not exceed recommended dose and frequency. Minimize risk of ptosis with careful monitoring (e.g., examining upper lid for separation or weakness of the levator palpebrae muscle, evaluating range of eyelid excursion, identifying lash ptosis) and adherence to manufacturer's recommended dosages and injection techniques. (See Injection Techniques [Glabellar Facial Lines] under Dosage and Administration.)

Preexisting Neuromuscular Disorders

Risk of adverse effects (e.g., severe dysphagia and/or respiratory compromise) with usual dosages of abobotulinumtoxinA appears to be increased in patients with neuromuscular disorders (e.g., peripheral motor neuropathic diseases [e.g., amyotrophic lateral sclerosis, motor neuropathy] or neuromuscular junction disorders [e.g., myasthenia gravis, Lambert-Eaton syndrome]); closely monitor such patients.

Risk of Viral Transmission

Preparation contains albumin derived from human blood. Remote risk of transmission of Creutzfeldt-Jakob disease (CJD) and other viral diseases via albumin component; however, no cases identified to date.

Immunogenicity

Potential immunogenicity. Development of binding or neutralizing antibodies reported in a few patients receiving abobotulinumtoxinA. Clinical importance not established.

Antibodies may reduce therapeutic effect; however, some patients with neutralizing antibodies continue to respond to the drug. Certain botulinum toxin preparations may be more likely to elicit an immune response.

Reporting Adverse Effects or Overdosage

If the patient receives an overdose of abobotulinumtoxinA or the drug is injected into the wrong muscle (i.e., misinjection), contact the local or state health department to process a request for botulism antitoxin through the CDC Drug Service. If a response is not received within 30 minutes, contact the CDC Emergency Operations Center directly at 770-488-7100. Information about the antitoxin is available at [Web].

Botulism antitoxin will not reverse any botulinum toxin-induced muscle weakness evident at the time of antitoxin administration but may stabilize the deficits.

Specific Populations

Pregnancy

No adequate and well-controlled clinical studies with abobotulinumtoxinA in pregnant women. Reproduction studies in rats and rabbits using abobotulinumtoxinA at dosages lower than or similar to the maximum recommended human dose have shown embryofetal toxic effects (e.g., early embryonic death, stillbirth) in relation to maternal toxicity.

Use during pregnancy only if potential benefit justifies potential risk to the fetus.

Lactation

Not known whether distributed into milk.

Pediatric Use

Manufacturer states that safety and efficacy not established in patients <18 years of age with cervical dystonia.

Not recommended for cosmetic improvement of glabellar lines in patients <18 years of age.

Geriatric Use

Insufficient experience in patients ≥65 years of age with cervical dystonia to determine whether such patients respond differently than younger adults; select dosage with caution due to age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.

Efficacy for glabellar lines not observed in individuals ≥65 years of age. Higher incidence of ocular adverse effects observed in geriatric compared with younger individuals.

No overall differences in efficacy or safety observed in geriatric individuals receiving abobotulinumtoxinA for upper limb spasticity compared with that in younger adults; cannot rule out possibility that some older patients may exhibit increased sensitivity to the drug.

Higher incidence of adverse effects observed in geriatric individuals receiving abobotulinumtoxinA for lower limb spasticity compared with younger adults (46 versus 39%). Fall and asthenia occurred more frequently in older patients as compared with younger patients.

Race/Ethnicity

Response rates in African Americans (with Fitzpatrick skin types IV–VI) and Hispanic patients with glabellar facial lines appear to be similar to those observed in the general population.

Common Adverse Effects

Cervical dystonia in adults: Muscular weakness, dysphagia, dry mouth, injection site discomfort, fatigue, headache, musculoskeletal pain, dysphonia, injection site pain, eye disorders (blurred vision, diplopia, reduced visual acuity and accommodation).

Glabellar facial lines in adults: Nasopharyngitis, headache, injection site pain, injection site reaction, upper respiratory tract infection, eyelid edema, ptosis, sinusitis, nausea, hematuria.

Spasticity (upper limb) in adults: Nasopharyngitis, muscular weakness, urinary tract infection, musculoskeletal pain, dizziness, fall, convulsion (seizure), depression, influenza, infection, pain in extremity, back pain, headache, syncope, hypoesthesia, partial seizures, fatigue, asthenia, injury, contusion, diarrhea, nausea, constipation, increased blood triglycerides, cough, hypertension.

Spasticity (lower limb) in adults: Falls, muscular weakness, pain in extremity.

Lower limb spasticity in pediatric patients ≥2 years of age: Upper respiratory tract infection, nasopharyngitis, influenza, pharyngitis, cough, pyrexia.

Drug Interactions

No formal drug interaction studies to date.

Specific Drugs

AbobotulinumtoxinA Pharmacokinetics

Absorption

Bioavailability

Not detectable in peripheral circulation following IM administration.

Duration

Cervical dystonia: Usual duration of effect ≥12–16 weeks or more.

Glabellar lines: Median duration of effect approximately 85 days following single IM injections of 50 units; reductions in glabellar line severity may be observed for up to 4 months.

Stability

Storage

Parenteral

Powder for Injection

2–8°C; protect from light.

Following reconstitution, store at 2–8°C and use within 4 hours; do not freeze.

Actions

• Purified neurotoxin type A complex produced by fermentation of Clostridium botulinum (Hall strain). Differs from other currently available preparations of botulinum toxin type A in molecular size, pharmacologic properties, dosing requirements, and adverse effect profile. (See Lack of Interchangeability Among Botulinum Toxin Preparations under Cautions.)

• Disrupts neurotransmission by inhibiting release of acetylcholine at peripheral cholinergic nerve terminals, inducing a chemical denervation and reduction of muscle activity.

• Neurotoxic effects occur in 3 phases: binding, internalization, and inhibition of acetylcholine from nerve terminals resulting in neuromuscular blockade.

• May also have a direct analgesic effect through modulation of certain peptide neurotransmitters.

• Weakness or paralysis of adjacent or distant muscles may occur as a result of toxin diffusion.

• Recovery of neuromuscular activity occurs slowly through regeneration and recovery of nerve endings.

Advice to Patients

• Importance of providing a copy of the FDA-approved medication guide and reviewing its contents with every patient. Instruct patients to read medication guide prior to initiation of therapy and each time prescription is refilled.

• Advise patients and/or caregivers to seek immediate medical attention if unexpected muscle weakness, swallowing, speech, or respiratory disorders occur, or if any existing symptoms worsen or persist.

• Advise patients that abobotulinumtoxinA can cause loss of strength, muscle weakness, blurred vision, or drooping eyelids, and that they should not drive a car, operate machinery, or engage in any other potentially hazardous activities during treatment.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses (e.g., neuromuscular disorders).

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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Frequently asked questions

• What is botulinum toxin used to treat?

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