Source: European Medicines Agency (EU) Revision Year: 2021 Publisher: Sloan Pharma S.à.r.l., 33, Rue du Puits Romain, 8070 Bertrange, Luxembourg
Individuals with known neuromuscular diseases (e.g. amyotrophic lateral sclerosis or peripheral neuropathy) or known neuromuscular junctional disorders (e.g. myasthenia gravis or Lambert-Eaton syndrome) must not be given NeuroBloc.
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
NeuroBloc is recommended for intramuscular administration only.
The safety of NeuroBloc outside the approved indication has not been established. This warning includes use in children and in any other indication besides cervical dystonia. The risks, which can include death, may outweigh the potential benefits.
As with many biological/biotechnology proteins used as therapeutic agents, repeated administration of NeuroBloc may be associated with development of antibodies to Botulinum Toxin Type B in some patients. Immunogenicity data from three long term clinical studies indicate that approximately one third of patients develop antibodies, as determined by the mouse neutralisation/mouse protection assay dependent on duration of exposure (see section 5.1).
An investigation into the consequence of seroconversion showed that the presence of antibodies was not synonymous with a loss of clinical response, and did not have an impact on the overall safety profile. However, the clinical relevance of the presence of antibodies as determined by the mouse neutralisation/mouse protection assay is uncertain.
Caution should be used in patients with bleeding disorders or receiving anticoagulant therapy.
Neuromuscular effects related to spread of toxin, distant from the site of administration have been reported (see section 4.8). These include dysphagia and breathing difficulties.
Patients treated with therapeutic doses may experience exaggerated muscle weakness. Patients with neuromuscular disorders may be at increased risk of clinically significant effects including severe dysphagia and respiratory compromise from typical doses of NeuroBloc (see section 4.3).
There have been spontaneous reports of dysphagia, aspiration pneumonia and/or potentially fatal respiratory disease, after treatment with Botulinum Toxin Type A/B.
Children (non approved use) and patients with underlying neuromuscular disorders including swallowing disorders are at increased risk of these adverse reactions. In patients with neuromuscular disorders or history of dysphagia and aspiration, botulinum toxins should only be used in an experimental setting under strict medical supervision.
Following NeuroBloc treatment, all patients and caregivers should be advised to seek medical attention for respiratory difficulties, choking or any new or worsening dysphagia.
Dysphagia has been reported following injection to sites other than the cervical musculature.
The initial starting dose of 10,000 U (or 5000 U) is relevant only to NeuroBloc (Botulinum Toxin Type B). These dose units are specific to NeuroBloc only and are not relevant to preparations of Botulinum Toxin Type A. The unit dose recommendations for Botulinum Toxin Type A are significantly lower than those for NeuroBloc and administration of Botulinum Toxin Type A at the unit dose recommended for NeuroBloc may result in systemic toxicity and life-threatening clinical sequelae.
The effect of administering different botulinum neurotoxin serotypes concurrently is unknown. However, in clinical studies, NeuroBloc was administered 16 weeks after the injection of Botulinum Toxin Type A.
Co-administration of NeuroBloc and aminoglycosides or agents interfering with neuromuscular transmission (e.g. curare-like compounds) should be considered with caution.
Animal reproduction studies are insufficient with respect to effects on pregnancy and embryonal/foetal development. The potential risk for humans is unknown. NeuroBloc should not be used during pregnancy unless the clinical condition of the woman requires treatment with Botulinum Toxin Type B (see section 5.3).
It is unknown whether Botulinum Toxin Type B is excreted in human breast milk. The excretion of Botulinum Toxin Type B in milk has not been studied in animals. A decision must be made on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with NeuroBloc taking into account the benefit of breast-feeding to the child and the benefit of NeuroBloc therapy to the woman.
No fertility studies have been performed and it is not known whether NeuroBloc can affect reproduction capacity.
No studies on the effects on the ability to drive and use machines have been performed. Neurobloc may impair the ability to drive or operate machinery in case of adverse reactions such as muscle weakness and eye disorders (blurred vision, eyelid ptosis).
The most commonly reported adverse reactions associated with NeuroBloc treatment were dry mouth, dysphagia, dyspepsia, and injection site pain.
Adverse reactions related to spread of toxin distant from the site of administration have been reported: exaggerated muscle weakness, dysphagia, dyspnoea, aspiration pneumonia with fatal outcome in some cases (see section 4.4).
Adverse reactions seen in all clinical studies are listed below according to MedDRA system organ class and in decreasing frequency which is defined as follows: Very Common (>1/10); Common (>1/100 to <1/10); Uncommon (>1/1000 to <1/100).
| System Organ Class | Very Common | Common |
|---|---|---|
| Nervous system disorders | dry mouth, headache | torticollis (worsening from baseline), taste perversion |
| Eye disorders | blurred vision | |
| Respiratory thoracic and mediastinal disorders | dysphonia | |
| Gastrointestinal disorders | dysphagia | dyspepsia |
| Musculoskeletal connective tissue and bone disorders | myasthenia | |
| General disorders and administration site conditions | injection site pain | neck pain influenza like illness |
In common with Botulinum Toxin Type A, electrophysiological jitter, which is not associated with clinical weakness or other electrophysiological abnormalities, may be experienced in some distant muscles.
Side effects related to spread of toxin distant from the site of administration have been reported (exaggerated muscle weakness, dysphagia, dyspnoea, aspiration pneumonia with fatal outcome in some cases) (see section 4.4).
The following effects have also been reported during post marketing use: abnormal accommodation, dry eye, ptosis, vomiting, constipation, flu-like symptoms, asthenia, angioedema, rash, urticaria and pruritus.
The available reports indicate that the product has been used in the paediatric population. Case reports are more likely to be serious in children (40%) compared to those in adults and older people (12%), possibly as a result of using an inappropriately high dosage for the child (see section 4.9).
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
