Currently Enrolling Trials
Xeomin is a Clostridium botulinum type - A neurotoxin complex. Clostridium botulinum toxin type A is a bacterial toxin that prevents nerves from functioning normally (a neurotoxin). It prevents nerves from releasing a chemical called acetylcholine, which is essential for the nerves to communicate with muscle cells. This toxin therefore prevents muscles from receiving nerve stimulation. Botulinum toxin type A causes muscle paralysis until such time as the nerve develops new endings to communicate with the muscles. This it is useful for treating conditions where excessive nerve stimulation to muscles is causing abnormal muscle functioning or spasms.
Xeomin is specifically indicated for the following:
- the treatment of cervical dystonia and blepharospasm
- the temporary improvement in the appearance of moderate to severe glabellar lines in adults
- the treatment of upper limb spasticity in adults
- the treatment of chronic sialorrhea, or excessive drooling, in patients aged 2 years and older with chronic sialorrhea, or drooling
- the first-line treatment of blepharospasm (involuntary blinking) in adults
Xeomin is supplied as a solution for intramuscular or intraglandular use. The recommended initial doses are as follows:
- Chronic Sialorrhea in Adults: the recommended total dose is 100 Units per treatment session consisting of 30 Units per parotid gland and 20 Units per submandibular gland, no sooner than every 16 weeks
- Chronic Sialorrhea in Pediatric Patients: the recommended dose is based on body weight administered in a 3:2 dose ratio into the parotid and submandibular glands, respectively, no sooner than every 16 weeks; ultrasound guidance recommended
Upper limb spasticity, cervical dystonia, and blepharospasm: the optimum dose, frequency, and number of injection sites in the treated muscle(s) should be based on severity and prior treatment response; individualize dosing for each patient:
- Upper Limb Spasticity in Adults: the recommended total dose is up to 400 Units, divided among affected muscles
- Upper Limb Spasticity in Pediatric Patients, excluding spasticity caused by cerebral palsy: the recommended total dose is 8 Units/kg (maximum 200 Units) per single upper limb or 16 Units/kg (maximum 400 U) in both upper limbs, divided among affected muscles
- Cervical Dystonia: the recommended initial total dose is 120 Units per treatment session
- Blepharospasm: the recommended initial total dose is 50 Units (25 Units per eye)
Glabellar Lines: the recommended dose is 20 Units per treatment session, divided into five equal intramuscular injections of 4 Units each (two injections in each corrugator muscle and one injection in the procerus muscle; wait a minimum of three months before retreatment
The FDA approval of Xeomin was based on the following studies:
A randomized, double-blind, placebo-controlled, multi-center phase III trial enrolled 233 patients with cervical dystonia. The baseline Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score ≥20, TWSTRS severity score ≥10, TWSTRS disability score ≥3, and TWSTRS pain score ≥1. The subjects received a single administration of Xeomin 240 Units (n=81), Xeomin 120 Units (n=78), or placebo (n=74). The investigator at each site decided which muscles would receive injections of Xeomin, the number of injection sites, and the volume at each site. The primary efficacy endpoint was the change in the TWSTRS total score from baseline to Week 4 post-injection. In the ITT population, the difference between the Xeomin 240 Unit group and the placebo group in the change of the TWSTRS total score from baseline to Week 4 was -9.0 points; the difference between the Xeomin 120 Unit group and the placebo group in the change of the TWSTRS total score from baseline to Week 4 was -7.5 points. Both results were statistically significant over placebo (p<0.001).
A randomized, double-blind, placebo-controlled, multi-center phase III trial enrolled 109 patients with blepharospasm. The baseline Jankovic Rating Scale (JRS) Severity subscore ≥2, and a stable satisfactory therapeutic response to previous administrations of onabotulinumtoxinA (Botox). At least 10 weeks had to have elapsed since the most recent onabotulinumtoxinA administration. The subjects were randomized to receive a single administration of Xeomin or placebo. The Xeomin treatment (dose, volume, dilution, and injection sites per muscle) that was similar to the most recent onabotulinumtoxinA injection sessions prior to study entry. The highest dose permitted in this study was 50 Units per eye; the mean Xeomin dose was 33 Units per eye. The primary efficacy endpoint was the change in the JRS Severity subscore from baseline to Week 6 post-injection. The difference between the Xeomin arm and the placebo arm in the change of the JRS Severity subscore from baseline to Week 6 was -1.0 (p<0.001).
Adverse events associated with the use of Xeomin for cervical dystonia may include, but are not limited to, the following:
- Neck pain
- Muscle weakness
- Injection site pain
- Musculoskeletal pain
Adverse events associated with the use of Xeomin for blepharospasm may include, but are not limited to, the following:
- Eyelid ptosis
- Dry eye
- Dry mouth
- Visual impairment
- Respiratory tract infection
Adverse events associated with the use of Xeomin for chronic sialorrhea may include, but are not limited to, the following:
- Chronic Sialorrhea in Adults (≥4% of patients): tooth extraction, dry mouth, diarrhea, and hypertension
- Chronic Sialorrhea in Pediatric Patients (≥1% of patients): bronchitis, headache, and nausea/vomiting
Adverse events associated with the use of Xeomin for spasticity may include, but are not limited to, the following:
- Upper Limb Spasticity in Adults (≥2% of patients): seizure, nasopharyngitis, dry mouth, and upper respiratory tract infection
- Upper Limb Spasticity in Pediatric Patients (≥3% of patients): nasopharyngitis and bronchitis
Adverse events associated with the use of Xeomin for glabellar lines may include, but are not limited to, the following: headache
The Xeomin drug label comes with the following Black Box Warning: The effects of Xeomin and all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. 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. The risk of symptoms is probably greatest in children treated for spasticity but symptoms can also occur in adults, particularly in those patients who have underlying conditions that would predispose them to these symptoms.
Mechanism of Action
Xeomin blocks cholinergic transmission at the neuromuscular junction by inhibiting the release of acetylcholine from peripheral cholinergic nerve endings. This inhibition occurs according to the following sequence: neurotoxin binding to cholinergic nerve terminals, internalization of the neurotoxin into the nerve terminal, translocation of the light-chain part of the molecule into the cytosol of the nerve terminal, and enzymatic cleavage of SNAP25, a presynaptic target protein essential for the release of acetylcholine. Impulse transmission is re-established by the formation of new nerve endings.
For additional information regarding Xeomin, please visit the Xeomin website.