Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use
"Traceability:
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded

General
Prior to administering XEOMIN, the physician must familiarise himself/herself with the patient’s anatomy and any alterations to the anatomy due to prior surgical procedures.

Care should be taken to ensure that XEOMIN is not injected into a blood vessel.

It should be taken into consideration that horizontal forehead lines may not only be dynamic, but may also result from the loss of dermal elasticity (e.g. associated with aging or photodamage). In this case, patients may not respond to Botulinum toxin products.

XEOMIN should be used with caution:
•     if bleeding disorders of any type exist
•     in patients receiving anticoagulant therapy or other substances that could have an anticoagulant effect.
The clinical effects of botulinum neurotoxin type A may increase or decrease by repeated injections.
The possible reasons for changes in clinical effects are different techniques of reconstitution, the chosen injection intervals, the injection sites and marginally varying toxin activity resulting from the biological testing procedure employed or secondary non-response.

Local and distant spread of toxin effect
Undesirable effects may occur from misplaced injections of botulinum neurotoxin type A that temporarily paralyse nearby muscle groups. Large doses may cause paralysis in muscles distant from the injection site.

There have been reports of undesirable effects that might be related to the spread of botulinum toxin type A to sites distant from the injection site (see section 4.8). Some of these can be life threatening and there have been reports of death, which in some cases was associated with dysphagia, pneumonia and/or significant debility.

Patients treated with therapeutic doses may experience excessive muscle weakness.
Patients or caregivers should be advised to seek immediate medical care if swallowing, speech or respiratory disorders occur.

Dysphagia has also been reported following injection to sites other than the cervical musculature.

Pre-existing neuromuscular disorders
Patients with neuromuscular disorders may be at increased risk of excessive muscle weakness particular when treated intramuscularly. The botulinum toxin type A product should be used under specialist supervision in these patients and should only be used if the benefit of treatment is considered to outweigh the risk.
Generally, patients with a history of aspiration or dysphagia should be treated with caution. Extreme caution should be exercised when treating these patients for cervical dystonia.

XEOMIN should be used with caution:
•   in patients suffering from amyotrophic lateral sclerosis
•   in patients with other diseases which result in peripheral neuromuscular dysfunction •     in targeted muscles which display pronounced weakness or atrophy 
Hypersensitivity reactions
Hypersensitivity reactions have been reported with botulinum neurotoxin type A products. If serious (e.g. anaphylactic reactions) and/or immediate hypersensitivity reactions occur, appropriate medical therapy should be instituted.

Antibody formation
Too frequent doses may increase the risk of antibody formation, which can result in treatment failure (see section 4.2).
The potential for antibody formation may be minimised by injecting with the lowest effective dose at the longest intervals between injections as clinically indicated.

Paediatric population
Spontaneous reports of possible distant spread of toxin have been very rarely reported for other preparations of Botulinum toxin type A in paediatric patients with comorbidities, predominantly with cerebral palsy. In general the dose used in these cases was in excess of that recommended for these products.
There have been rare spontaneous reports of death sometimes associated with aspiration pneumonia in children with severe cerebral palsy after treatment with botulinum toxin products, including following off label use (e.g. neck area). The risk is considered particularly high in paediatric patients with a poor underlying health status or in patients who have significant neurologic debility, dysphagia, or in patients who have a recent history of aspiration pneumonia or lung disease.
Indication-specific warnings

Blepharospasm
Injections near the levator palpebrae superioris muscle should be avoided to reduce the occurrence of ptosis. Diplopia may develop as a result of botulinum neurotoxin type A diffusion into the inferior oblique muscle. Avoiding medial injections into the lower lid may reduce this adverse reaction.

Because of the anticholinergic effect of botulinum neurotoxin type A, XEOMIN should be used with caution in patients at risk of developing a narrow angle glaucoma.

In order to prevent ectropion, injections into the lower lid area should be avoided, and vigorous treatment of any epithelial defect is necessary. This may require protective drops, ointments, soft bandage contact lenses, or closure of the eye by patching or similar means.

Reduced blinking following XEOMIN injection into the orbicularis muscle can lead to corneal exposure, persistent epithelial defects and corneal ulceration, especially in patients with cranial nerve disorders (facial nerve). Careful testing of corneal sensation should be performed in patients with previous eye operations.

Ecchymosis easily occurs in the soft tissues of the eyelid. Immediate gentle pressure at the injection site can limit that risk.

Spasmodic torticollis
XEOMIN should be injected carefully when injecting at sites close to sensitive structures such as the carotid artery, lung apices and oesophagus.

Previously akinetic or sedentary patients should be reminded to gradually resume activities following the injection of XEOMIN.

Patients should be informed that injections of XEOMIN for the management of spasmodic torticollis may cause mild to severe dysphagia with the risk of aspiration and dyspnoea. Medical intervention may be necessary (e.g. in the form of a gastric feeding tube) (see also section 4.8). Limiting the dose injected into the sternocleidomastoid muscle to less than 100 units may decrease the occurrence of dysphagia.
Patients with smaller neck muscle mass, or patients who require bilateral injections into the sternocleidomastoid muscles are at greater risk. The occurrence of dysphagia is attributable to the spread of the pharmacological effect of XEOMIN as the result of the neurotoxin spread into the oesophageal musculature.

Post-stroke Spasticity of the upper limb
XEOMIN should be injected carefully when injecting at sites close to sensitive structures such as the carotid artery lung apices and oesophagus.

Previously akinetic or sedentary patients should be reminded to gradually resume activities following the injection of XEOMIN.

XEOMIN as a treatment for focal spasticity has been studied in association with usual standard care regimens, and is not intended as a replacement for these treatment modalities. XEOMIN is not likely to be effective in improving range of motion at a joint affected by a fixed contracture.

New onset or recurrent seizures have been reported, typically in patients who are predisposed to experiencing these events. The exact relationship of these events to botulinum toxin injection has not been established.

Effects on Driving

4.7   Effects on ability to drive and use machines

XEOMIN has a minor or moderate influence on the ability to drive and use machines. Patients should be counselled that if asthenia, muscle weakness, dizziness, vision disorders or drooping eyelids occur, they should avoid driving or engaging in other potentially hazardous activities.