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.

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. These preparations are not interchangeable; assay methods used to determine potency of botulinum toxins are specific to each individual manufacturer and/or formulation.

IncobotulinumtoxinA contains pure neurotoxin without any complexing proteins (hemagglutinins and nonhemaglutinins). Not established whether this formulation difference is associated with therapeutic benefit compared with other botulinum toxin preparations.

Upper Limb Spasticity

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

Data indicate that incobotulinumtoxinA improves muscle tone and spasticity-associated disability. 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.

Cervical Dystonia

Treatment of cervical dystonia (spasmodic torticollis); indicated for use in both previously treated and untreated (botulinum toxin-naive) adults.

Appears to be as effective as onabotulinumtoxinA when given in comparable doses.

Botulinum toxins are considered a treatment of choice for cervical dystonia.

Blepharospasm

Treatment of blepharospasm in patients previously treated with onabotulinumtoxinA (Botox). Efficacy and safety of incobotulinumtoxinA in patients not previously treated with onabotulinumtoxinA not established.

AAN states that a botulinum toxin should be considered as a treatment option for patients with blepharospasm.

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.

Efficacy appears similar to onabotulinumtoxinA when given in equivalent doses.

Related/similar drugs

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

IncobotulinumtoxinA Dosage and Administration

General

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

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

Administration

IM Administration

Administer by IM injection into affected muscles.

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

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

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

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

Reconstitution

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

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

Preservative-free 0.9% sodium chloride injection.

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

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

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.

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

Injection Techniques/Precautions (Cervical Dystonia)

Administer total dose as several injections divided among affected muscles. 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.

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.

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

Injection Techniques/Precautions (Blepharospasm)

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

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

Do not inject into medial lower eyelid area to prevent ectropion. (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.

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

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

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.

Adults

Upper Limb Spasticity

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 incobotulinumtoxinA.

Use of EMG recommended to guide injections.

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

Cervical Dystonia

IM

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

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

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.

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

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.

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

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

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).

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

Dosing not established in patients not previously treated with onabotulinumtoxinA.

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).

May repeat treatments at intervals of ≥3 months.

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

Prescribing Limits

Adults

Upper Limb Spasticity

IM

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

Cervical Dystonia

IM

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

Blepharospasm

IM

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

Glabellar Facial Lines

IM

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

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.

• Infection at injection site.

Warnings/Precautions

Warnings

Distant Spread of Toxin Effects

Potential for distant spread of toxin effects beyond local sites of injection. (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.

In some cases, severe swallowing or breathing difficulties required hospitalization, ventilatory support, or gastric feeding tube and/or resulted in death. (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).

Sensitivity Reactions

Hypersensitivity Reactions

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

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

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.

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

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

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. Gastric feeding tube may be required to support adequate nutrition and hydration.

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.

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.

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

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

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

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

Risk of Ptosis

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

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

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. Neutralizing antibodies reported in approximately 1% of patients receiving incobotulinumtoxinA in clinical studies; however, long-term immunogenicity remains to be established.

Preclinical studies demonstrated reduced antigenicity with incobotulinumtoxinA versus onabotulinumtoxinA; however, further study needed to confirm this finding.

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. 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

Category C.

No adequate and well-controlled clinical studies with incobotulinumtoxinA in pregnant women. 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.

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

Lactation

Not known whether distributed into milk. Caution advised.

Pediatric Use

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

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.

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.

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.

Common Adverse Effects

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

Cervical dystonia: Dysphagia, neck pain, muscle weakness, injection site pain, musculoskeletal pain.

Blepharospasm: Eyelid ptosis, dry eye, dry mouth, diarrhea, headache, visual impairment, dyspnea, nasopharyngitis, respiratory tract infection.

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

Drug Interactions

No formal drug interaction studies performed to date.

Specific Drugs

IncobotulinumtoxinA Pharmacokinetics

Absorption

Bioavailability

Not detectable in peripheral circulation following IM administration.

Duration

Usual duration of effect ≤3 months.

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).

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

Actions

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

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

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

• 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.

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

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 to seek immediate medical attention if any swallowing, speech, or respiratory difficulties arise.

• Advise immobile or sedentary patients to gradually resume activities following treatment with incobotulinumtoxinA for cervical dystonia or blepharospasm.

• Inform patients that incobotulinumtoxinA may cause dyspnea or dysphagia with associated risk of aspiration.

• 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.

• 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.

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

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

• 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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