NEUROBLOC

NeuroBloc should only be administered by a physician who is familiar with and experience in the treatment of cervical dystonia and in the use of botulinum toxins. Restricted to hospital use only. Posology The initial dose is 10,000 U and should be divided between the two to four most affected muscles.

Data from clinical studies suggest that efficacy is dose dependent, but these trials, because they were not powered for a comparison, do not show a significant difference between 5000 U and 10,000 U. Therefore an initial dose of 5000 U may also be considered, but a dose of 10,000 U may increase the likelihood of clinical benefit.

Injections should be repeated as required to maintain good function and minimise pain. In long term clinical studies, the average dosing frequency was approximately every 12 weeks, however this may vary between subjects, and a proportion of patients maintained a significant improvement relative to baseline for 16 weeks or longer.

The dosing frequency should therefore be adapted based on the clinical assessment/response of an individual patient. For patients with reduced muscle mass the dose should be adjusted according to individual patient need. The potency of this medicinal product is expressed in NeuroBloc 5000 U/ml.

4). Special populations Elderly No dose adjustment is required in older people ≥ 65 years of age. Renal and hepatic impairment Studies have not been carried out in patients with hepatic or renal impairment. However, the pharmacological characteristics do not indicate any need to adjust the dose.

Paediatric population The safety and efficacy of NeuroBloc in children aged less than 18 years have not yet been established. No data are available. Method of administration NeuroBloc must only be administered by intramuscular injection.

Particular caution should be paid to ensure that it is not injected into a blood vessel. The initial dose of 10,000 U should be divided between the two to four most affected muscles. 9%) solution for injection and the solution used immediately.

6.

Summary of the safety profile The most commonly reported adverse reactions associated with NeuroBloc treatment were dry mouth, dysphagia, dyspepsia, and injection site pain. 4). Tabulated list of adverse reactions 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.

4). The following effects have also been reported during post marketing use: abnormal accommodation, 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.

9). Reporting of suspected adverse reactions 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.

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. Seroconversion 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.

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. 8). These include dysphagia and breathing difficulties. Pre-Existing neuromuscular disorders Patients treated with therapeutic doses may experience exaggerated muscle weakness.

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. Lack of interchangeability between botulinum toxin products The initial starting dose of 10,000 U (or 5000 U) is relevant only to NeuroBloc (Botulinum Toxin Type B).

g. g. myasthenia gravis or Lambert-Eaton syndrome) must not be given NeuroBloc. 1.