Xeomin (IncobotulinumtoxinA) is a purified form of botulinum neurotoxin (compared to BOTOX injection that contains proteins) that acts as a muscle relaxant when administered locally in the muscles.

It is used in spastic conditions such as dystonia and torticollis. However, it is commonly used for cosmetic purposes to reduce the glabellar line (to reduce frowning), and wrinkles.

IncobotulinumtoxinA (Xeomin) Uses:

• US labeling:

  • Glabellar lines:

    • A transient reduction in the formation of moderate to severe glabellar lines in association with adult corrugator and/or procerus muscle activation.

  • Blepharospasm:

    • Treatment of adults with blepharospasm.

  • Upper limb spasticity:

    • Adult patients' upper limb spasticity treatment.

  • Cervical dystonia:

    • Therapy of adults who suffer from cervical dystonia.

  • Sialorrhea:

    • Adult persistent sialorrhea treatment.

• Canadian labeling:

  • Xeomin:

    • Cervical dystonia:

      • Therapy of cervical dystonia (spasmodic torticollis) affected adults.

    • Hypertonicity disorders: T

      • Treatment for adult patients with hypertonicity diseases of the 7th nerve, such as hemifacial and blepharospasm.

    • Upper limb spasticity:

      • Adults' post-stroke upper limb spasticity treatment.

  • Xeomin Cosmetic:

    • Glabellar lines:

      • A momentary lessening of the patients' moderate to severe glabellar lines' intensity.

IncobotulinumtoxinA dose in adults:

Xeomin Dose in the therapy of Blepharospasm: IM:

US labeling:

• Treatment naive:

  • Initial: 25 units per eye (50 units in a single treatment session);
  • 50 units maximum dosage per eye (100 units total per treatment session).
  • Give further shots no more frequently than every three months.

• Treatment experienced:

  • The overall dose shouldn't exceed 100 units every treatment session.

Canadian labeling:

• Initial: 1.25 to 2.5 units per injection site (maximum initial dose of 25 units of the total in one eye for patients who have never had treatment; 35 units in one eye for patients who have received an unknown dose in the past).
• Titrate dose and interval for maximum patient benefit.
• The overall dose shouldn't exceed 100 units every treatment session.
• Administer no more often than three months apart.

Xeomin Dose in the treatment of Cervical dystonia: IM:

• US labeling:

  • Initial total dose: 120 units (in clinical trials, patients with and without prior therapy exhibited similar levels of effectiveness with initial total doses of 120 and 240 units, respectively).
  • The severity of the condition, the response to prior therapies, the duration of the effect, any adverse events detected, and the number and location of  the afflicted muscle determine the dosage and the number of injection sites (s).
  • Most participants in clinical studies received between 2 and 10 injections into the targeted muscles.
  • Administering should only occur every three months or less.
  • 400 units are the maximum cumulative dose per treatment session.

• Canadian labeling:

  • The maximum total dose is 300 units, and the maximum dose per injection site is 50 units. The recommended administration frequency is no more than three times per year.

Xeomin Dose in the treatment of Reduction of glabellar lines:

• IM: For a total of 20 units in a single treatment session, inject 4 units into each of the five locations (2 injections into each corrugator muscle and 1 injection into the procerus muscle).
• Administer no more often than three months apart.

Xeomin Dose in the treatment of Sialorrhea:

• Intraglandular:
  • 100 units total should be injected into the parotid and submandibular glands on both sides, dividing the dose in a 3:2 ratio between them (i.e., 4  injection sites in a single treatment session).
• Depending on clinical need, the course of treatment may be repeated no sooner than every 16 weeks.

Xeomin Dose in the therapy of Upper limb spasticity: IM:

• US labeling:

  • Start with a modest dose and gradually increase it based on the patient's condition.
  • The base dosage, frequency, and the number of injection sites are all influenced by the size, number, and position of the muscles that need to be treated,  the degree of spasticity that is present, the presence of a localized muscular weakness, the patient's response to previous treatment, and the history of adverse events.
  • Administer no more often than three months apart.
  • 400 units are the maximum cumulative dose per treatment session.

  • Clenched fist:

    • Flexor digitorum superficialis or flexor digitorum profundus:
      • Separated into two injection sites, 25 to 100 units

  • Pronated forearm:

    • Pronator teres:
      • 25 to 75 units total dose divided into 1 to 2 injections
    • Pronator quadratus:
      • 10 to 50 units of dose in 1 injection

  • • Thumb-in-palm:

      • Adductor pollicis:
        • 5 to 30 units of dose in 1 injection
      • Flexor pollicis longus:
        • 10 to 50 units of dose in 1 injection
      • Flexor pollicis brevis/opponens pollicis:
        • 5 to 30 units of dose in 1 injection
  •  

  • Flexed wrist:

    • Flexor carpi radialis:
      • 25 to 100 units total dose divided into 1 to 2 injection sites
    • Flexor carpi ulnaris:
      • 20 to 100 units total dose divided into 1 to 2 injection sites

  • Flexed elbow:

    • Biceps:
      • 50 to 200 units total dose divided into 1 to 4 injection sites
    • Brachioradialis:
      • 25 to 100 units total dose divided into 1 to 3 injection sites
    • Brachialis:
      • 25 to 100 units total dose divided into 1 to 2 injection sites

• Canadian labeling:

  • Start dosage at the lowest range and titrate as needed for the patient's condition. administer no more often than three months apart.
  • A single treatment session shouldn't use more than 400 units of the entire dose.

  • Flexed wrist:

    • The total initial dose of 90 units

  • Clenched fist:

    • Total initial dose is 80 units

  • Flexor carpi radialis:

    • Initial dose 50 units; subsequent dose range 25 to 100 units of total divided into 1 to 2 injection sites

  • Flexor carpi ulnaris:

    • Initial dose 40 units; subsequent dose range 20 to 100 units of total divided into 1 to 2 injection sites

  • Flexor digitorum superficialis:

    • Initial dose 40 units; subsequent dose range 40 to 100 units of total divided into 2 injection sites

  • Flexor digitorum profundus:

    • Initial dose 40 units; subsequent dose range 40 to 100 units of total divided into 2 injection sites

  • Flexed elbow:

    • The total initial dose of 130 to 190 units

  • Brachioradialis:

    • Initial dose 60 units; subsequent dose range 25 to 100 units of total divided into 1 to 3 injection sites

  • Biceps:

    • Initial dose 80 units; subsequent dose range 75 to 200 units of total divided into 1 to 4 injection sites

  • Brachialis:

    • Initial dose 50 units; subsequent dose range 25 to 100 units of total divided into 1 to 2 injection sites

  • Pronated forearm:

    • The total initial dose of 25 to 65 units

  • Pronator quadratus:

    • Initial dose 25 units; subsequent dose range 10 to 50 units of the total in 1 injection

  • Pronator teres:

    • Initial dose 40 units; subsequent dose range 25 to 75 units of total divided into 1 to 2 injections

  • Thumb-in-palm:

    • The total initial dose of 10 to 40 units

  • Flexor pollicis longus:

    • Initial dose 20 units; subsequent dose range 10 to 50 units of the total in 1 injection

  • Adductor pollicis:

    • Initial dose 10 units; subsequent dose range 5 to 30 units of the total in 1 injection

  • Flexor pollicis brevis/ opponens pollicis:

    • Initial dose 10 units; subsequent dose range 5 to 30 units of the total in 1 injection

Pregnancy Risk Category: C

• In some studies on animal reproduction, adverse events were reported.

IncobotulinumtoxinA use during breastfeeding:

• It is unknown if breast milk contains incobotulinumtoxinA.
• Canadian labeling does NOT recommend breastfeeding.

Xeomin Dose in Kidney Disease:

• There are no dosage adjustments provided in the drug manufacturer's labeling.

Xeomin Dose in Liver disease:

• There are no dosage adjustments provided in the drug manufacturer's labeling.

Upper limb spasticity and cervical dystonia:

Common Side Effects of Xeomin (IncobotulinumtoxinA):

• Central nervous system:

  • Myasthenia

• Gastrointestinal:

  • Dysphagia

• Infection:

  • Infection

• Neuromuscular & skeletal:

  • Neck pain

• Respiratory:

  • Respiratory system disorder

Less Common Side Effects of Xeomin (IncobotulinumtoxinA):

• Central nervous system:

  • Seizure

• Gastrointestinal:

  • Xerostomia

• Immunologic:

  • Antibody development

• Local:

  • Pain at injection site

• Neuromuscular & skeletal:

  • Musculoskeletal pain

• Respiratory:

  • Nasopharyngitis
  • Upper respiratory tract infection

Blepharospasm, chronic sialorrhea, and glabellar lines:

Common Side Effects of IncobotulinumtoxinA (Xeomin):

• Gastrointestinal:

  • Xerostomia

• Ophthalmic:

  • Blepharoptosis
  • Dry eye syndrome
  • Visual disturbance

Less Common Side Effects of IncobotulinumtoxinA (Xeomin):

• Cardiovascular:

  • Hypertension

• Central nervous system:

  • Headache
  • Falling
  • Voice disorder

• Gastrointestinal:

  • Diarrhea
  • Tooth loss

• Neuromuscular & skeletal:

  • Back pain

• Respiratory:

  • Dyspnea
  • Nasopharyngitis
  • Respiratory tract infection
  • Bronchitis

Contraindications to Xeomin (IncobotulinumtoxinA):

• Hypersensitivity to any of the formulation's ingredients or to botulinum toxins
• Infection of planned injection site(s)
• Canadian labeling: Additional contraindications not in US labeling
  • General abnormalities of muscle activity (eg myasthenia gravis or Lambert-Eaton syndrome).

Warnings and precautions

• Anaphylaxis or hypersensitivity reactions

  • Severe hypersensitivity, such as anaphylactic reactions, serum sickness, urticaria, and soft-tissue swelling, may occur. If you notice any signs or symptoms of hypersensitivity, discontinue treatment immediately. You should seek immediate medical attention.

• Cardiovascular events

  • Rarely, the use of another botulinum-toxin product has been associated with arrhythmia or cardiac damage. Occasionally, persons with a history of heart illness will exhibit this.

• Formation of antibodies:

  • Increased doses, frequent administration, and/or the onset of disease earlier may lead to neutralizing antibodies and loss of efficacy.

• CNS depression:

  • The intended effects of treatment may cause impairment in driving and/or operating machinery.
  • Patients should not drive or engage in other dangerous activities if they encounter loss of muscles, feebleness, or eyesight concerns.

• Dysphagia

  • A feature of cervical dystonia. may happen immediately or after weeks. They might last for several months. In severe circumstances, patients might need to be fed via alternative techniques.
  • Two-way injections into the sternocleidomastoid muscles and a smaller neck muscle mass are risk factors.
  • Limiting the dose of medication that is administered to the sternocleidomastoid muscles may reduce dysphagia.

• Hematologic:

  • Patients should exercise caution if they have bleeding issues or are using anticoagulant medication.

• Systemic toxicities: [US Boxed Warning]

  • There has been evidence of botulinum poison spreading beyond the injection site. This can lead to breathing problems and difficulty swallowing. Other signs and symptoms include double vision, dysphonia, dysarthria, and widespread weakening of the muscles. urinary incontinence and drooping eyelids that may develop in a matter of hours or even weeks. 
    Children who are treated for spasticity that is not approved by their parents may be at greater risk.
  • There have been systemic reactions to both approved and unapproved uses of the drug, even in low doses.
  • Patients with underlying conditions should be cautious if they are experiencing these symptoms.
  • If you have swallowing, speech, or respiratory problems, seek immediate medical attention.

• Neuromuscular disease

  • Patients with neuropathic illnesses (such as amyotrophic lateral syndrome) and neuromuscular conditions such as myasthenia gravis or Lambert-Eaton syndrome should exercise caution. These conditions are prohibited in Canada.
  • There may be an increase in the risk of severe dysphagia or respiratory compromise.

• Ocular diseases

  • Injections into the muscle of the orbicularis can cause decreased blinking, which can result in corneal exposure and even ulceration.
  • It is important to test the cornea for sensitivity and avoid lower lid injections.
  • It may be beneficial to use soft contact lenses for therapeutic purposes, eye protection drops, ointment application, or to cover the troubled eye.
  • The possibility of bruising the eyelids may be reduced by lightly pressing the injection site.
  • Patients with angle-closure eye disease should be cautious

• Respiratory disease

  • Patients with pre-existing respiratory diseases should exercise extreme caution. The accessory muscles required for proper breathing may become paralyzed or weakened as a result of botulinum toxin treatment for cervical dystonia.
  • Patients with severe dysphagia are at greater risk of aspiration due to their reduced respiratory function.

IncobotulinumtoxinA (Xeomin): Drug Interaction

Monitor for respiratory depression and motor weakness. 

How to administer Xeomin (IncobotulinumtoxinA)?

• IM: Note: If the prospective injection sites have been indicated with a pen, avoid injecting through those marks because it could result in a permanent tattoo.

Blepharospasm:

• Use a needle that is 12.5 mm long and 30 gauge.
• Electromyography does not need to be guided. When injecting, avoid the levator palpebrae superioris (which may decrease ptosis).
• Avoid injecting the medial lower lid (may decrease ectropion).
• Apply pressure to the injection site to prevent ecchymosis in the supple eyelid tissues.

Cervical dystonia and upper limb spasticity:

• Use a 22-gauge needle (75 mm length) for deeper musculature and a 26-gauge needle (37 mm length) for superficial muscles. To help identify the afflicted muscles, electromyography or nerve stimulation may be performed.
• The Canadian labeling advises against administering bilateral injections or doses to the sternocleidomastoid muscle that exceeds 100 units (increased risk of adverse events, particularly dysphagia).

Reduction of glabellar lines:

• Use a needle that is 13 mm long and 30-33 gauge.

• In order to lessen ptosis, it is best to avoid injections close to the levator palpebrae superioris. A centimeter or so above the bone supraorbital ridge is the recommended placement for corrugator injections.

Intraglandular: Sialorrhea:

• Use a needle that is 12.5 mm long and 27-30 gauge.
• Use ultrasonic imaging or surface anatomical features to find the salivary glands.

Mechanism of action of Xeomin (IncobotulinumtoxinA):

• Acetylcholine release at peripheral cholinergic nerve terminals is inhibited by the neurotoxin Clostridium botulinumtoxinA, which is produced by the bacterium Clostridium botulinum.
• The sequential process of inhibition includes the internalization and binding of the neurotoxin to presynaptic cholinergic nervous terminals, the migration of the cytosol within the nerve terminal, and the enzymatic destruction of SNAP25, a protein necessary for acetylcholine release.
• A state of denervation is caused by the inhibition of acetylcholine production at the neuromuscular junction.
• Up until now nerve-derived fibrils and junction plates are generated on fresh patches of muscle-cell walls, and muscular inactivation persists.

Absorption:

• After IM injection, it is not anticipated to be present in peripheral blood at the indicated levels.

Duration:

• ~3 to 4 months

The onset of action (improvement):

• ~4 to 7 days

International Brands of IncobotulinumtoxinA:

• Xeomin
• Xeomin Cosmetic
• Xeomeen

IncobotulinumtoxinA Brand Names in Pakistan:

No Brands Available in Pakistan.