Dosing and uses of Xeomin (incobotulinumtoxinA)
Adult dosage forms and strengths
lyophilized powder for reconstitution
- 50 units/vial
- 100 units/vial
- 200 units/vial
Upper Limb Spasticity
Indicated for the treatment of upper limb spasticity in adults
Dosage, frequency, and number of injection sites should be tailored to the individual patient based on the size, number, and location of muscles to be treated, severity of spasticity, presence of local muscle weakness, patient’s response to previous treatment, and adverse event history with incobotulinumtoxinA
The frequency of treatments should be no sooner than every 12 weeks
If previously treated with botulinum toxins, initial dosing should begin at the low end of the recommended dosing range and titrated as clinically necessary
Do not exceed cumulative dose of 400 units per 12-wk intervaL
Recommended dose per muscle
- Clenched fist
- Flexor digitorum superficialis: 25-100 units divided in 2 sites
- Flexor digitorum profundus: 25-100 units divided in 2 sites
- Flexed wrist
- Flexor carpi radialis: 25-100 units divided in 1-2 sites
- Flexor carpi ulnaris: 20-100 units divided in 1-2 sites
- Flexed elbow
- Brachioradialis: 25-100 units divided in 1-3 sites
- Biceps: 50-200 units divided in 1-4 sites
- Brachialis: 25-100 units divided in 1-2 sites
- Pronated forearm
- Pronator quadratus: 10-50 units in 1 site
- Pronator teres: 25-75 units divided in 1-2 sites
- Thumb-in-palm
- Flexor pollicis longus: 10-50 units in 1 site
- Adductor pollicis: 5-30 units in 1 site
- Flexor pollicis brevis/Opponens pollicis: 5-30 units in 1 site
Cervical Dystonia
Indicated to decrease the severity of abnormal head position and neck pain in both botulinum toxin-naive and previously treated patients
Optimum dose and number of injection sites in treated muscle(s) individualized for each patient as determined by Md
Total dose is 120 units IM per treatment session; higher doses not shown to provide additional efficacy and were associated with increased adverse effects
Usually injected into sternocleidomastoid, splenius capitis, levator scapulae, scalenus, and/or trapezius muscles(s)
Blepharospasm
Indicated for blepharospasm in patients who were previously treated with onabotulinumtoxinA (Botox)
Optimum dose and number of injection sites in treated muscle(s) individualized for each patient as determined by Md
Dose, number, and location of injections should be based on the previous dosing of onabotulinumtoxinA (Botox)
Do not administer to patients who have not previously received onabotulinumtoxinA
If previous dose of onabotulinumtoxinA unknown, the recommended starting dose is 1.25-2.5 units IM per injection site
In clinical trials, the mean dose per injection site was 5.6 units, the mean number of injections per eye was 6, and the mean dose per eye was 33.5 units
Glabellar Lines
Indicated for temporary improvement of moderate-to-severe glabellar lines associated with corrugator and/or procerus muscle activity
Total dose is 20 units per treatment session divided into 5 equal IM injections of 4 units each (2 injections in each corrugator muscle and 1 injection in procerus muscle)
Retreat no more frequently than q3months
Pediatric dosage forms and strengths
Safety and efficacy not established
Xeomin (incobotulinumtoxinA) adverse (side) effects
>10%
Cervical dystonia
- Nervous system disorders (16%)
- Dysphagia (13%)
- Respiratory, thoracic, and mediastinal disorders (13%)
Blepharospasm
- Eyelid ptosis (19%)
- Dry eye (16%)
- Xerostomia (16%)
- Nervous system disorders (14%)
- Visual impairment, including blurred vision (12%)
- Respiratory, thoracic, and mediastinal disorders (11%)
1-10%
Cervical dystonia
- Injection site pain (9%)
- Neck pain (7%)
- Muscular weakness (7%)
- Musculoskeletal pain (7%)
Blepharospasm
- Diarrhea (8%)
- Headache (7%)
- Dyspnea (5%)
- Nasopharyngitis (5%)
- Respiratory tract infection (5%)
Glabellar lines
- Headache (5.4%)
Postmarketing Reports
Allergic disorders: Hypersensitivity, eye swelling/edema, allergic dermatitis
Gastroenterology: Nausea
Body as a whole: Flu-like symptoms
Local reactions: Injection site pain, injection site reaction, localized allergic reactions (eg, swelling, edema, erythema, pruritus, rash)
Infection: Herpes zoster
Musculoskeletal: Muscular weakness, muscle spasm, myalgia
Neurologic: Dysarthria, dysphagia
Warnings
Black box warnings
Distant spread of toxin effect
- Botulinum toxin products may spread from injected area to produce symptoms consistent with botulinum toxin effects (eg, asthenia, generalized muscle weakness, diplopia, blurred vision, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence, respiratory distress)
- 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
- Greatest risk in children treated for spasticity
- Can also occur in adults, particularly in those with underlying conditions that would predispose them to these symptoms (eg, peripheral motor neuropathic diseases, amyotrophic lateral sclerosis, or neuromuscular junctional disorders [myasthenia gravis, Lambert-Eaton syndrome])
Contraindications
Hypersensitivity
Infection at proposed injection site(s)
Cautions
Dose NOT interchangeable with other botulinum toxin products
Can cause swallowing and breathing difficulties, caution with compromised respiratory function or dysphagia
Concomitant neuromuscular disorders may exacerbate adverse effects
Discontinue and immediately initiate medical therapy if hypersensitivity reaction occurs (eg, anaphylaxis, serum sickness, urticaria, edema, dyspnea)
Cervical dystonia
- Patients with smaller neck muscle mass and patients who require bilateral injections into the sternocleidomastoid muscles are at greater risk of dysphagia
- Limit dose injected into the sternocleidomastoid muscle may decrease the occurrence of dysphagia
Blepharospasm
- Do not administer to patients who have not previously received onabotulinumtoxinA (Botox)
- Injection into orbicularis oculi muscle may lead to reduced blinking and corneal exposure with possible ulceration or perforation
- Lower lid injections should not be repeated if diplopia occurred with previous botulinum toxin injections
Glabellar lines
- Risk of ptosis
Pregnancy and lactation
Pregnancy category: C; based on animal data, may cause fetal harm
Lactation: Unknown whether distributed in breast milk, do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Xeomin (incobotulinumtoxinA)
Mechanism of action
Blocks cholinergic transmission at the neuromuscular junction by inhibiting acetylcholine release from the peripheral cholinergic nerve endings
Pharmacokinetics
Onset of action: 4-7 days
Duration: 3-4 months
Absorption: Absence from peripheral blood at recimmended IM injections
Administration
IM Preparation & Dilution
Prior to injection, reconstitute each vial with sterile, preservative-free 0.9% NaCl Injection USp
Draw up an appropriate amount of 0.9% NaCl to result in desired units/0.1 mL (per Manufacturer’s instructions)
Clean the exposed portion of the vial’s rubber stopper with 70% alcohol prior to needle insertion
Gently inject the 0.9% NaCl into the viaL
If the vacuum does not pull the solvent into the vial, then vial must be discarded (vacuum seal compromised)
Gently mix with the saline by rotating the vial (do not shake to prevent flocculation)
Reconstituted solution should be clear, colorless, and free of particulate matter
Do not use if reconstituted solution is cloudy or contains floccular or particulate matter
IM Administration
For intramuscular (IM) injection only
After reconstitution, use for only 1 injection session and for only 1patient
Select suitable sterile needle for administration (eg, 26-gauge, 37 mm length for superficial muscles; or 22-gauge, 75 mm length for injections into deeper muscles)
Localization of the involved muscles with electromyographic guidance or nerve stimulation techniques may be usefuL
If proposed injection sites are marked with a pen, the product must not be injected through the pen marks; otherwise a permanent tattooing effect may occur
Number of injection sites is dependent upon the size of the muscle to be treated and the volume of reconstituted incobotulinumtoxinA injected
Inject carefully when administration sites are close to sensitive structures (eg, carotid artery, lung apices, esophagus)
Physician should be familiar with the patient’s anatomy and any anatomic alterations due to prior surgical procedures.
Storage
May store unopened vials at room temperature, refrigerated, or frozen for up to 36 months (not to exceed expiration date)
Reconstituted vials should be refrigerated and administered within 24 hr
