IncobotulinumtoxinA (Monograph)

Brand name: Xeomin
Drug class: Botulinum toxins
Chemical name: Botulinum Toxin A
Molecular formula: C₂₂₈₆H₃₅₀₀N₅₇₈O₆₆₆S₉ (light chain) C₄₄₂₂H₆₈₆₃N₁₁₅₁O₁₃₂₉S₂₃ (heavy chain).
CAS number: 93384-43-1

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.^{403 405 407 411}

Uses for IncobotulinumtoxinA

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.^{1 2 5 384 403 411 414} These preparations are not interchangeable; assay methods used to determine potency of botulinum toxins are specific to each individual manufacturer and/or formulation.^{1 2 5 381 384 403 405 407 408 409 410 411 413 414 418 421}

IncobotulinumtoxinA contains pure neurotoxin without any complexing proteins (hemagglutinins and nonhemaglutinins).^{405 407 408 411 414} Not established whether this formulation difference is associated with therapeutic benefit compared with other botulinum toxin preparations.^{408 409 411 413 414}

Upper Limb Spasticity

Treatment of upper limb spasticity; safety and efficacy based on studies in adults who had experienced a stroke ≥3 months previously.^{403 430 431}

Data indicate that incobotulinumtoxinA improves muscle tone and spasticity-associated disability.^{403 430 431} The American Academy of Neurology (AAN) recommends therapy with a botulinum toxin for the treatment of focal manifestations of spasticity involving upper limbs in adults.⁵⁰⁰

Cervical Dystonia

Treatment of cervical dystonia (spasmodic torticollis);^{387 391 403 405 406 408 411} indicated for use in both previously treated and untreated (botulinum toxin-naive) adults.^{403 405 406 411}

Appears to be as effective as onabotulinumtoxinA when given in comparable doses.^{405 408}

Botulinum toxins are considered a treatment of choice for cervical dystonia.^{53 387 391 405 406 408 415 500}

Blepharospasm

Treatment of blepharospasm in patients previously treated with onabotulinumtoxinA (Botox).^{387 391 403 408 409 413 414 416} Efficacy and safety of incobotulinumtoxinA in patients not previously treated with onabotulinumtoxinA not established.⁴⁰³

AAN states that a botulinum toxin should be considered as a treatment option for patients with blepharospasm.^{415 500}

Cosmesis of Glabellar Facial Lines

Temporary improvement in the appearance of moderate to severe glabellar facial (“frown”) lines associated with corrugator and/or procerus muscle activity in adults.^{396 403 417 418}

Efficacy appears similar to onabotulinumtoxinA when given in equivalent doses.⁴¹⁷

IncobotulinumtoxinA Dosage and Administration

General

• Individualize dosage according to patient response and condition being treated.⁴⁰³ Consider other factors such as severity of disease, number of muscles involved, muscle mass, and previous response to other botulinum toxin therapy.⁴⁰³

• The effects of a single treatment usually last ≤3 months, but may be considerably longer or shorter depending on the individual.⁴⁰³ If repeat treatments required, manufacturer recommends ≥12 weeks between treatment sessions.⁴⁰³

Administration

IM Administration

Administer by IM injection into affected muscles.⁴⁰³

Clinicians who administer incobotulinumtoxinA should be familiar with the relevant neuromuscular and/or orbital anatomy of the therapeutic target area.⁴⁰³

Exercise caution when injecting into areas in close proximity to sensitive structures (e.g., carotid artery, lung apices, esophagus).⁴⁰³

When proposed injection sites are marked with ink, avoid direct injection into these areas to avoid permanent tattooing of the skin.⁴⁰³

Monitor for sudden swallowing or respiratory difficulties during or following administration.^{381 403} (See Distant Spread of Toxin Effects under Cautions.)

Reconstitution

Reconstitute lyophilized drug with preservative-free 0.9% sodium chloride injection prior to administration.⁴⁰³

Add appropriate amount of diluent to vial to provide desired dose (see Table 1).⁴⁰³ A vacuum should draw in the diluent; discard vial if vacuum is absent.⁴⁰³ Gently rotate until powder is completely dissolved.⁴⁰³

Preservative-free 0.9% sodium chloride injection.

Use reconstituted solutions immediately or store at 2–8°C for ≤24 hours.⁴⁰³

Use reconstituted solution for a single treatment session and for only one patient.⁴⁰³ Carefully discard any unused portions as medical waste.⁴⁰³

Injection Techniques/Precautions (Upper Limb Spasticity)

Use a suitable sterile needle (e.g., 26-gauge, 37-mm length needle for superficial muscles or 22-gauge, 75-mm length needle for deeper muscles) for injections.⁴⁰³

Electromyogram (EMG) guidance or nerve stimulation techniques may be helpful in locating target injection sites.⁴⁰³

Injection Techniques/Precautions (Cervical Dystonia)

Administer total dose as several injections divided among affected muscles.⁴⁰³ Usual injection sites include sternocleidomastoid, levator scapulae, splenius capitis, scalenus, and/or trapezius muscles, although treatment may be required in any muscle involved in the control of head position.⁴⁰³

Use a suitable sterile needle (e.g., 26-gauge, 37-mm length needle for superficial muscles or 22-gauge, 75-mm length needle for deeper muscles) for injections.⁴⁰³

EMG guidance or nerve stimulation techniques may be helpful in locating target injection sites.⁴⁰³

Injection Techniques/Precautions (Blepharospasm)

Use a suitable sterile needle (e.g., 30-gauge, 12.5-mm length needle) for injections.⁴⁰³

Reduce or prevent ecchymosis by applying gentle pressure to the injection site immediately postinjection.⁴⁰³

Do not inject into medial lower eyelid area to prevent ectropion.⁴⁰³ (See Ocular Effects in Patients with Blepharospasm under Cautions.)

Injection Techniques/Precautions (Glabellar Facial Lines)

Divide total dose at each treatment session into 5 equal injections; administer 2 injections in each corrugator muscle and 1 in the procerus muscle.⁴⁰³

Use a suitable sterile 30- to 33-gauge, 13-mm length needle for injections.⁴⁰³

To minimize risk of ptosis, avoid injections near the levator palpebrae superioris, especially in individuals with larger brow-depressor complexes.⁴⁰³ Injections into the medial corrugator muscle should be ≥1 cm above the bony supraorbital ridge.⁴⁰³ (See Risk of Ptosis under Cautions.)

Dosage

Potency of incobotulinumtoxinA expressed in units of biologic activity; each unit is equivalent to the median intraperitoneal lethal dose (LD₅₀) in mice.^{403 407}

Units of biologic activity of incobotulinumtoxinA cannot be compared with or converted to units of other botulinum toxin preparations; assay methods used to determine potency of various botulinum toxin preparations are specific to each individual preparation.⁴⁰³

Adults

Upper Limb Spasticity

IM

Manufacturer-recommended doses and muscles to be injected shown in Table 2.⁴⁰³

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 incobotulinumtoxinA.⁴⁰³

Use of EMG recommended to guide injections.⁴⁰³

Use lowest recommended starting dose in patients not previously treated with botulinum toxins and titrate as clinically necessary.⁴⁰³

Cervical Dystonia

IM

Previously treated and botulinum-toxin naive patients: Initially, 120 units as a divided dose among affected muscles.⁴⁰³

Whenever possible, use minimum effective dosage to reduce risk of adverse effects and maintain responsiveness to drug.⁴⁰³ Limit total dose injected into sternocleidomastoid muscle to decrease risk of dysphagia.⁴⁰³

In clinical studies, median doses of 25, 48, 25, 25, and 20 units were administered to the sternocleidomastoid, splenius capitis/semispinalis capitis, trapezium, levator scapulae, and scalenus (medius and anterior) muscles, respectively.^{403 411}

May repeat treatments at intervals of ≥12 weeks; determine frequency of repeat treatments by clinical response.⁴⁰³

Blepharospasm

IM

Previously treated patients: Initial dose should be the same as the patient's previous dose of onabotulinumtoxinA (Botox); dosing requirements may vary depending on individual response.⁴⁰³

If previous dose of onabotulinumtoxinA not known, give initial doses of 1.25–2.5 units at each site.⁴⁰³

Individualize subsequent dose based on patient response.⁴⁰³ Total dose administered during the initial or any subsequent treatment session should be ≤70 units (or 35 units per eye).⁴⁰³

In clinical trials, mean dose was 33.5 units per eye (range 10–50 units); mean number of injections was 6 per eye (average dose of 5.6 units in each site).⁴⁰³

May repeat treatments at intervals of ≥12 weeks; determine frequency of repeat treatments by clinical response.⁴⁰³

Dosing not established in patients not previously treated with onabotulinumtoxinA.⁴⁰³

Glabellar Facial Lines

IM

Total dose of 20 units per treatment session, divided into 5 equal injections of 4 units each (2 into each corrugator muscle and one in the procerus muscle).⁴⁰³

May repeat treatments at intervals of ≥3 months.⁴⁰³

Do not exceed recommended dose and frequency to minimize risk of ptosis.⁴⁰³

Prescribing Limits

Adults

Upper Limb Spasticity

IM

Manufacturer states that maximum cumulative dose per treatment session for any indication is 400 units.⁴⁰³

Cervical Dystonia

IM

Initial doses >120 units not shown to provide additional efficacy and may be associated with increased incidence of adverse effects.⁴⁰³ Manufacturer states that maximum cumulative dose per treatment session for any indication is 400 units.⁴⁰³

Blepharospasm

IM

Total initial dose of 70 units (or 35 units per eye).⁴⁰³

Glabellar Facial Lines

IM

Do not repeat treatments more frequently than once every 3 months.⁴⁰³

Cautions for IncobotulinumtoxinA

Contraindications

• Known hypersensitivity (e.g., anaphylaxis, serum sickness, urticaria, soft tissue edema, dyspnea) to any botulinum toxin preparation or ingredient (e.g., albumin, sucrose) in their formulations.⁴⁰³

• Infection at injection site.⁴⁰³

Warnings/Precautions

Warnings

Distant Spread of Toxin Effects

Potential for distant spread of toxin effects beyond local sites of injection.^{381 403} (See Boxed Warning.)

Serious adverse effects consistent with mechanism of botulinum toxin action (e.g., dysphagia, dysarthria, generalized muscle weakness, ptosis, blurred vision, diplopia, respiratory compromise, speech difficulties, urinary incontinence) reported.^{381 403}

In some cases, severe swallowing or breathing difficulties required hospitalization, ventilatory support, or gastric feeding tube and/or resulted in death.^{381 403} (See Dysphagia/Breathing Difficulties under Cautions.)

Risk of toxin spread probably highest in children treated for spasticity (currently not an FDA-labeled use for incobotulinumtoxinA).^{381 383 384 403 410}

Sensitivity Reactions

Hypersensitivity Reactions

Potential risk of hypersensitivity.⁴⁰³ (See Contraindications under Cautions.)

If a serious and/or immediate hypersensitivity reaction occurs, discontinue further injection and initiate appropriate medical therapy.⁴⁰³

Other Warnings/Precautions

Lack of Interchangeability Among Botulinum Toxin Preparations

The method used to determine potency (“units”) of incobotulinumtoxinA is specific to the Xeomin preparation; therefore, units of biologic activity for incobotulinumtoxinA cannot be compared with or converted to units of any other botulinum toxin preparation.⁴⁰³

Dysphagia/Breathing Difficulties

Risk of dysphagia in patients receiving a botulinum toxin for cervical dystonia.^{381 383 403 405 411 412} Usually a consequence of cervical muscle weakening from local areas of injection, but also may be related to distant spread of toxin effects.^{381 403} (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.⁴⁰³ Aspiration and death reported as a complication of severe dysphagia.^{381 383 403}

Patients with smaller neck muscle mass or who require bilateral injections into the sternocleidomastoid muscles appear to be at greater risk.⁴⁰³ (See Dosage under Dosage and Administration.)

Use with caution in patients with dysphagia.⁴⁰³ Risk of aspiration is increased in patients with compromised swallowing function.⁴⁰³

Immediate medical attention may be required if sudden speech or swallowing difficulties develop during or following treatment; such effects may occur hours to weeks after injection.⁴⁰³ Gastric feeding tube may be required to support adequate nutrition and hydration.⁴⁰³

Preexisting Neuromuscular Disorders

Risk of adverse effects (e.g., severe dysphagia and/or respiratory compromise) may 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.⁴⁰³

Ocular Effects in Patients with Blepharospasm

Risk of corneal exposure, corneal ulceration, and ectropion following injections of botulinum toxins into the orbicularis muscle, particularly in patients with seventh cranial nerve disorders.⁴⁰³

Carefully evaluate for corneal sensation in those with prior eye surgery.⁴⁰³ To decrease risk of ectropion, avoid injection of lower lid area.^{403 414} Aggressively treat any epithelial defect with protective drops, ointments, therapeutic soft contact lenses, or closure of the eye by patching or other means.⁴⁰³

Use with caution in patients at risk of developing angle-closure glaucoma.⁴⁰³

Limit risk of ecchymosis by immediately applying gentle pressure at the injection site.⁴⁰³

Do not repeat injections into lower lid if diplopia has occurred with previous botulinum toxin therapy.⁴⁰³

Risk of Ptosis

To minimize risk of ptosis, avoid injections near the levator palpebrae superioris, especially in individuals with larger brow-depressor complexes.⁴⁰³ Injections into the corrugator muscle should be placed ≥1 cm above the bony superior orbital margin.⁴⁰³

Do not exceed recommended dose and frequency in patients receiving the drug for glabellar lines.⁴⁰³

Risk of Viral Transmission

Preparation contains albumin derived from human blood.⁴⁰³ Remote risk of transmission of Creutzfeldt-Jakob disease (CJD) and other viral diseases via albumin component; however, no cases identified to date.⁴⁰³

Immunogenicity

Potential immunogenicity.^{403 412} Neutralizing antibodies reported in approximately 1% of patients receiving incobotulinumtoxinA in clinical studies;⁴¹² however, long-term immunogenicity remains to be established.^{405 414}

Preclinical studies demonstrated reduced antigenicity with incobotulinumtoxinA versus onabotulinumtoxinA; however, further study needed to confirm this finding.^{407 408 411 414}

Reporting Adverse Effects or Overdosage

If the patient receives an overdose of incobotulinumtoxinA 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.⁴⁰³ If a response is not received within 30 minutes, contact the CDC Emergency Operations Center directly at 770-488-7100.⁴⁰³ 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.⁴⁰³

Specific Populations

Pregnancy

Category C.⁴⁰³

No adequate and well-controlled clinical studies with incobotulinumtoxinA in pregnant women.⁴⁰³ Increased rate of abortion and embryotoxic effects (e.g., decreased fetal body weight, skeletal ossification) in relation to maternal toxicity observed in rats and rabbits treated with incobotulinumtoxinA at dosages exceeding maximum recommended human dose for cervical dystonia.⁴⁰³

Use during pregnancy only if potential benefit justifies potential risk to the fetus.⁴⁰³

Lactation

Not known whether distributed into milk.⁴⁰³ Caution advised.⁴⁰³

Pediatric Use

Manufacturer states that safety and efficacy not established in patients <18 years of age.⁴⁰³

Geriatric Use

Among geriatric patients >65 years of age included in clinical studies of incobotulinumtoxinA for upper limb spasticity, no overall differences in efficacy or safety were observed between geriatric and younger patients, and other clinical experience revealed no evidence of age-related differences; however, possibility that some older patients may exhibit increased sensitivity to the drug cannot be ruled out.⁴⁰³

Among geriatric patients >65 years of age included in clinical studies of incobotulinumtoxinA for cervical dystonia or blepharospasm, approximately 53–76% experienced an adverse event.⁴⁰³

A limited number of individuals ≥65 years of age were included in clinical studies of incobotulinumtoxinA for treatment of glabellar lines; efficacy was demonstrated in 20% of these individuals and no increase in adverse effects observed.⁴⁰³

Common Adverse Effects

Upper limb spasticity: seizure, nasopharyngitis, dry mouth, upper respiratory tract infection.⁴⁰³

Cervical dystonia: Dysphagia, neck pain, muscle weakness, injection site pain, musculoskeletal pain.^{403 405 407 408 411}

Blepharospasm: Eyelid ptosis, dry eye, dry mouth, diarrhea, headache, visual impairment, dyspnea, nasopharyngitis, respiratory tract infection.^{403 407 414}

Glabellar facial lines: Headache, facial paresis, injection site hematoma, eyelid edema.⁴⁰³

Drug Interactions

No formal drug interaction studies performed to date.⁴⁰³

Specific Drugs

IncobotulinumtoxinA Pharmacokinetics

Absorption

Bioavailability

Not detectable in peripheral circulation following IM administration.⁴⁰³

Duration

Usual duration of effect ≤3 months.⁴⁰³

Stability

Storage

Parenteral

Powder for Injection

Store unopened vials at room temperature (20–25°C), refrigerator (2–8°C), or freezer (-20 to -10°C).⁴⁰³

Following reconstitution, store at 2–8°C and use within 24 hours.⁴⁰³

Actions

• Purified neurotoxin type A complex produced by fermentation of Clostridium botulinum (Hall strain).^{403 405 407 411} Differs from other currently available botulinum toxin type A preparations in that it contains active neurotoxin without complexing accessory proteins (hemagglutinins and nonhemaglutinins).^{403 407 408 411}

• Disrupts neurotransmission by inhibiting release of acetylcholine at peripheral cholinergic nerve terminals, inducing a chemical denervation and muscle paralysis.^{403 408}

• Neurotoxic effects occur in 3 phases: binding, internalization, and inhibition of acetylcholine from nerve terminals resulting in neuromuscular blockade.⁴⁰³

• Causes temporary weakening or paralysis of muscles in local injection sites; however, adjacent or distant muscles also may be affected if spread of toxin effects occurs.^{381 403 408}

• Recovery of neuromuscular activity occurs through regeneration and recovery of nerve endings, usually within 3–4 months following an injection.⁴⁰³

Advice to Patients

• Importance of providing a copy of the FDA-approved medication guide and reviewing its contents with every patient.^{403 404} Instruct patients to read medication guide prior to initiation of therapy and each time prescription is refilled.^{403 404}

• Advise patients to seek immediate medical attention if any swallowing, speech, or respiratory difficulties arise.^{403 404}

• Advise immobile or sedentary patients to gradually resume activities following treatment with incobotulinumtoxinA for cervical dystonia or blepharospasm.^{403 404}

• Inform patients that incobotulinumtoxinA may cause dyspnea or dysphagia with associated risk of aspiration.^{403 404}

• Advise patients that incobotulinumtoxinA 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.^{403 404}

• Advise patients that incobotulinumtoxinA may cause reduced blinking or effectiveness of blinking and that they should seek immediate medical attention if eye pain or irritation occurs following treatment.^{403 404}

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{403 404}

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.^{403 404}

• Importance of informing patients of other important precautionary information.^{403 404} (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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