Botulinum A toxin

ArticlesRefrigerated StorageLactation Safety InformationNew Medicines ·
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Articles

Hypersalivation – what are the treatment alternatives to glycopyrronium and hyoscine?

This Medicines Q&A outlines possible alternatives to hyoscine hydrobromide and glycopyrronium in the treatment of non drug-induced hypersalivation, e.g. botulinum toxin, amitriptyline, atropine (eye drops… Administering Amitriptyline Atropine Benzatropine Botulinum A toxin Cisapride Dosing Glycopyrronium Hyoscine (base) Hyoscine hydrobromide Ipratropium Metoprolol Modafinil Neurological disorders Piracetam Propranolol Publications Ranitidine Rotigotine Trihexyphenidyl

Refrigerated Storage

BotoxAllergan Ltd.

Allergan Ltd.
Botox
Powder for solution for injection 50, 100, 200 units/vial

In the event of an inadvertent temperature excursion the following data may be used:

There is no effect on the stability of the product if it was not exposed to temperatures:
Outside a range of -70°C  to 30°C  for a period of no more than five days (120 hours)

Please also refer to the manufacturer’s product literature for recommended storage information at https://www.medicines.org.uk

The product should be returned to the fridge as soon as possible and marked "use first" if exposed to the storage conditions specified above.
7 May 2019
London MI Service

DysportIpsen Ltd.

Ipsen Ltd.
Dysport
Injection, vials containing 500 units or 300 units

Contact Ipsen in all cases where a deviation from the recommended storage conditions has occurred. Refer to the current BNF for company contact details.

Please also refer to the manufacturer’s product literature for recommended storage information at https://www.medicines.org.uk

No Information
No Information

Do not freeze

5 May 2020
London MI services

AzzalureGalderma

Galderma
Azzalure
125 units powder for solution for injection

In the event of an inadvertent temperature excursion the following data may be used:
Stability studies have been conducted on unreconstituted Azzalure at 25°C and 40°C for short periods, and these have shown that Azzalure remains stable at 25°C for up to two weeks and at 40°C for up to 24 hours.
Please also refer to the manufacturer’s product literature for recommended storage information at https://www.medicines.org.uk

Information not provided by manufacturer
Yes
19 December 2019
London Medicines Information Service

Lactation Safety Information

-
No published evidence of safety after therapeutic use. Botulism in a mother showed no transfer of toxin to infant via breast milk
No systemic absorption in mother if used correctly. Therefore, not expected to be found in breast milk
Delay cosmetic use until infant weaned
8 November 2018

New Medicines

DysportTreatment of upper limb spasticity in children aged 2 to 17 years

Information

Dysport
Licence extension / variation
Ipsen
Not Known

Development and Regulatory status

Launched
Launched
Launched
January 2020
Jan 20Approved in UK by MHRA for use in symptomatic treatment of focal spasticity of upper limbs in paediatric cerebral palsy (CP) patients, two years of age or older. Approval was based on a PIII study, which found that the drug reduced spasticity symptoms in children aged two years and older being treated for upper limb spasticity due to CP. The approval means the treatment is now the first and only botulinum toxin in the UK approved for the treatment of paediatric spasticity in both upper and lower limbs [5].
Sep 19Approved in the US for the treatment of upper limb spasticity in children aged ≥2 years, excluding spasticity caused by cerebral palsy [4].
Jun 19According to Ipsen pipeline, Dysport is pre-registration for paediatric upper limb spasticity; location not stated but assume US & EU [3].

Category

Glutamate receptor antagonist
Pooled data from five active cerebral palsy registers in the UK suggest a mean annual prevalence rate for normal birth-weight children of 1.2 per 1,000 live births [1].
Treatment of upper limb spasticity in children aged 2 to 17 years
Intramuscular

Trial or other data

Oct 18PIII PUL study has completed [2].
Apr 14PIII PUL study (NCT02106351) to assess the efficacy and safety of multiple doses of Dysport used in the treatment of upper limb spasticity (altered skeletal muscle performance) in children with cerebral palsy (CP) starts. 212 children aged 2 to 17 years will be recruited in the US, Belgium, Czechia, Israel, Mexico, Spain, Turkey and Poland. Collection of primary outcome data (Mean change from baseline in the Primary Targeted Muscle Group on Modified Ashworth Scale (MAS) at week 6) due to complete in Sep 17 [2].

DysportSpasmodic torticollis - solution for injection formulation

Information

Dysport
New formulation
Ipsen
Not Known

Development and Regulatory status

Discontinued
Discontinued
Discontinued
Jul 19Ipsen has decided not to progress this licence application for a new solution for injection in the EU [7].
Mar 19Company confirms there is no licence variation application currently under review; still in PIII development in EU [6].
Feb 19Still pre-registration in EU [5].
Mar 17Currently pre-registration in the EU [3].

Category

Glutamate receptor antagonist. 500units solution for injection formulation.
Torticollis, or wry neck, is a twisted neck. Acute torticollis is thought to be due to minor local musculoskeletal irritation causing pain and spasm in neck muscles [1]. Although acquired torticollis is one of the most common forms of dystonia, it remains a rare disorder. Prevalence has been estimated at 1 in 10,000 to 1 in 20,000 people in the general population [2].
Spasmodic torticollis - solution for injection formulation
Intramuscular

DysportTreatment of urinary incontinence in patients with neurogenic detrusor overactivity due to spinal cord injury or multiple sclerosis

Information

Dysport
Licence extension / variation
Ipsen
Not Known

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

Glutamate receptor antagonist. 600U (start dose) or 800U (highest dose) per treatment session, dosed no more frequently than every 12 weeks.
60-80% of people with MS and 75-80% of people with spinal cord injury will have some degree of bladder dysfunction including urinary incontinence [1].
Treatment of urinary incontinence in patients with neurogenic detrusor overactivity due to spinal cord injury or multiple sclerosis
Intramuscular

XeominSialorrhoea due to neurological causes in adults with Parkinson’s disease, stroke or traumatic brain injury

Information

Xeomin
Licence extension / variation
Merz Pharmaceuticals
Merz Pharmaceuticals

Development and Regulatory status

Launched
Launched
Launched
May 2019
May 19Approved in EU for symptomatic treatment of chronic sialorrhea due to neurological disorders in adults [9,10].
Nov 18Currently pre-registration in EU. Has been filed via the mutual recognition procedure [8].
Jul 18Approved in US [7].
Mar 18FDA accepts sBLA for Xeomin® (incobotulinumtoxinA) in adult patients with chronic sialorrhea due to Parkinson’s Disease or other neurological disorders [6].
Dec 17Will be filed in the EU via the mutual recognition procedure [5].

Category

Glutamate receptor antagonist
There are currently about 127,000 people with Parkinson’s disease in the UK whilst the prevalence of cerebral palsy is about 1 per 400 children.
Sialorrhoea due to neurological causes in adults with Parkinson’s disease, stroke or traumatic brain injury
Intramuscular

Further information

Yes
October 2019

Trial or other data

Jan 17The PIII NCT02091739 study has completed in Nov 16 [4].
Jan 16NCT02091739, the PIII study in adults, is ongoing but fully recruited. It is due to complete Nov 16. NCT02270736, the PIII study in children and adolescents, is still recruiting patients and is due to complete Jun 18 [3].
Dec 14PIII randomised, double-blind, placebo-controlled trial initiated in children and adolescents with chronic troublesome sialorrhoea associated with neurological disorders (e.g. cerebral palsy, traumatic brain injury) and/or intellectual disability. The study plans to enrol 249 patients, aged 2 to 17 years old in the US [2].
Mar 14NCT02091739 is a PIII, randomized, double-blind, placebo-controlled study, with an extension period of dose-blinded active treatment, to investigate the efficacy and safety of two dose levels (75 and 100 units) of NT 201 in treating 180 subjects with chronic troublesome sialorrhea due to neurological conditions (Parkinson´s disease, atypical Parkinsonism or after stroke or traumatic brain injury). The co-primary endpoints are change in unstimulated salivary flow rate and subject´s Global Impression of Change Scale (GICS) scores from baseline to 4 weeks. The study starts Mar 14 and is due to complete Jul 16 (primary data collection Apr 15) [1].

Evidence based evaluations

XeominTreatment of muscle spasticity in children and adolescents aged 2 to 17 years

Information

Xeomin
Licence extension / variation
Merz Pharmaceuticals
Merz Pharmaceuticals

Development and Regulatory status

None
Phase III Clinical Trials
None

Category

Glutamate receptor antagonist
Pooled data from five active cerebral palsy registers in the UK suggest a mean annual prevalence rate for normal birth-weight children of 1.2 per 1,000 live births [3].
Treatment of muscle spasticity in children and adolescents aged 2 to 17 years
Intramuscular

XeominChronic sialorrhoea due to neurological disorders in children

Information

Xeomin
Licence extension / variation
Merz Pharmaceuticals
Merz Pharmaceuticals

Development and Regulatory status

None
Phase III Clinical Trials
None

Category

Glutamate receptor antagonist
Prevalence of moderate-to-severe drooling in children, young people and adults with neurological conditions, particularly cerebral palsy, is estimated to be between 10% and 37% [1].
Chronic sialorrhoea due to neurological disorders in children
Intramuscular

Evidence based evaluations

XeominLower limb muscle spasticity following stroke or traumatic brain injury - first-line in adults

Information

Xeomin
Licence extension / variation
Merz Pharmaceuticals
Merz Pharmaceuticals

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

Glutamate receptor antagonist
In England, approximately 110,000 people have a stroke each year and between 19 and 38% of them (up to 41,800 people) are affected by spasticity. Of the people who have spasticity associated with stroke, 79% report spasticity in the elbow, 66% report spasticity in the wrist, 50% report spasticity in the hip, 54% report spasticity in the knee, and 66% report spasticity in the ankle [1].
Lower limb muscle spasticity following stroke or traumatic brain injury - first-line in adults
Intramuscular

Further information

Yes
To be confirmed

Botox Treatment of upper limb muscle spasticity in children aged 2 to 17 years with cerebral palsy and stroke

Information

Botox
Licence extension / variation
Allergan
Allergan

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Launched
Jun 19Approved in US for treatment of upper limb spasticity in children aged 2 to 17 years [1].

Category

Glutamate receptor antagonist
Cerebral palsy is the most common condition associated with spasticity in children and young people, although it can also occur with other forms of nonprogressive and progressive brain disorders. The incidence of cerebral palsy is not known, but its prevalence in the UK is 186 per 100,000 population, with a total of 110,000 people affected [2,3].
Treatment of upper limb muscle spasticity in children aged 2 to 17 years with cerebral palsy and stroke
Intramuscular

Trial or other data

Sep 18Allergan complete PIII trial (NCT01603615) of Botox for treatment of pediatric upper limb spasticity. A second PIII study (NCT01603602) completed June 17 [4].

Botox Treatment of lower limb muscle spasticity in children aged 2 to 17 years with cerebral palsy and stroke

Information

Botox
Licence extension / variation
Allergan
Allergan

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Launched
Oct 19FDA approves license extension for Botulinum A toxin for treatment of lower limb spasticity in children and adolescents aged 2 to 17 years [5].
Mar 19Filed in US for treatment of lower limb spasticity aged 2 to 17 years; a decision is expected Q4 2019 [1,2].

Category

Glutamate receptor antagonist
Cerebral palsy is the most common condition associated with spasticity in children and young people, although it can also occur with other forms of nonprogressive and progressive brain disorders. The incidence of cerebral palsy is not known, but its prevalence in the UK is 186 per 100,000 population, with a total of 110,000 people affected [3,4].
Treatment of lower limb muscle spasticity in children aged 2 to 17 years with cerebral palsy and stroke
Intramuscular

Evidence based evaluations